Tag Archives: lyme disease research

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Is the Clinical Trials Process Working?

GLA’s Chief Scientific Officer takes an important look at our current clinical trials process. Is it still working? Does it serve patient needs?


by Timothy J. Sellati, Ph.D., Chief Scientific Officer, Global Lyme Alliance

The first structured clinical trials date back to the 1940s, not counting the first recorded trial of legumes in biblical times.¹ A lot has happened in the world of science, illness and disease, and patient sophistication in the last 80 years—maybe it’s time to re-visit the clinical trials process, to ensure that there is a balance between scientific rigor and patient needs.

As of June 24, 2020, the novel coronavirus known as SARS-CoV-2 has infected over 9 million people globally.* More than 470,000 people have died as a direct or indirect result of the ensuing viral disease COVID-19. Lacking immunity to this new viral pathogen, a vaccine to protect against it, or drugs proven to treat it COVID-19 has swept across the globe virtually unchecked.

Not surprisingly, the worldwide scientific and medical research community along with governmental agencies and non-profit organizations and the pharmaceutical and biotechnology industries are frantically seeking effective drugs and a vaccine to interrupt the explosive spread of COVID-19 and protect the global population against future infection if SARS-CoV-2 becomes a seasonal epidemic.

The current COVID-19 pandemic, and our collective rush to find viable treatment or vaccine options, brings our current clinical trials process to the forefront of discussion. Is the process still viable? Does it help or hinder getting safe, effective options into the hands of the physicians and patients who need them? Or does it remind us of the value of a thorough, yet lengthy process to keep the community safe? How do we balance the importance of good science with the needs of patients? Just like science itself, it’s a process fraught with questions.

Do we need to rethink our drug and vaccine testing approach?

Given the devastating personal and financial chaos this new coronavirus pandemic has wreaked it is no wonder that the slow and methodical philosophy regarding the path to clinical study validation of new drugs and vaccines has come under scrutiny. An argument could and perhaps should be made for the need to revamp the clinical trial process. Doing so might better serve patients in general, and specifically would address the immediacy of need in situations like COVID-19 as well as serve patients suffering from chronic Lyme disease, where few if any treatment advances have been made over the last three decades.

When is “tried and true” not good enough?

Like many things in the healthcare world, there are traditional methods and philosophical beliefs that may be outdated, ineffective, and perhaps more detrimental to progress than understanding the mysteries of disease, the intricacies of scientific inquiry, and the validation of medicine itself. If you tell a cancer patient they have a 100% chance of dying or a 30% chance of survival, but they may lose a limb, or their ability to taste, or any other of a variety of side effects, 100% of those cancer patients with a terminal prognosis are likely to take the chance/risk associated with an untested drug. This scenario and the severity of the current global pandemic challenges the premise that we cannot or should not deviate from taking every single step on the laborious and time-consuming path toward clinical validation of a novel drug or new COVID-19 vaccine.

In many ways, the health challenges faced by a subset of Lyme disease patients, those suffering from persistent symptoms and chronic disease for months or years, provokes us to pose the same question. Every day, these patients are taking risks with a variety of potential treatments and symptom relief options, because they are desperate to feel better vs. enduring continued pain, loss of physical and mental function, and an overall diminished quality of life. Under such circumstances, many Lyme patients will risk the side effects for a chance at relief. Given this reality and despite a lack of traditional clinical trial evidence, one might argue that the medical community should be provided more leeway in exploring alternative treatment options to those proscribed by current standard of care guidelines.

Why should the “patient’s voice” be heard?

Sometimes, the need to eliminate any potential safety issues and identify all possible side effects should or needs to be secondary to a patient’s ability to decide for themselves, through consultation with their physician, whether to try a new, not entirely proven, treatment option. Recognition and acknowledgement by the healthcare community that it does not always have the answers, especially as it relates to how a patient truly feels or the risk they would be willing to take, is the first step in providing more options to patients desperate for relief.

What might we trade for exigent reasons?

Exigency refers to an urgent need or demand while expediency is the quality of being convenient and practical despite possibly being improper or immoral. Perhaps treatment choices should be guided less by the results of large, multi-site, double-blind, randomized, placebo-controlled clinical trials and more on a calculus of greater benefit than risk, where risk is perhaps not as low as traditionally sought. A “scaled back” clinical study design that identifies biomarkers of treatment efficacy or surrogates of vaccine-induced protection, and qualifying patient groups and their potential response to intervention to increase, though not ensure, the likelihood of treatment or prevention success will expedite approval and availability of desperately needed medical advances.

The current COVID-19 pandemic and the need for advancement in treatment options for Lyme disease requires seeking balance between exigency and expediency. Streamlining the process of clinical study/trial design and execution could accelerate the discovery of novel drugs, treatment regimens and vaccines. However, potential side effects or the fact that not everyone will benefit may be missed. If this is the outcome and harm is done, the maker of drugs or vaccines or the physician with a novel treatment regimen may need indemnification against individual or class action lawsuits. People who freely choose to take a drug or vaccine, with inherent greater risk, may need to cede the right, at least under some circumstances, to legal recourse if harmed.

1 Evolution of Clinical Research: A History Before and Beyond James Lind, Dr Arun Bhatt

*Updated. As of July 22, 2020, the novel coronavirus known as SARS-CoV-2 has infected more than 15 million people globally.

Additional POVs by GLA’s Science Leadership Team

Research Sharing: What Can Lyme Disease Learn from Skin Cancer?
Parallel Pandemics: COVID-19 and Lyme Disease
Research POV: Lyme Arthritis and Peptidoglycan
Pandemics, Ecology, and Food Production: Is There a Connection?
Essential Oils as Treatment Against Lyme Disease 
Antimicrobial Action of Calprotectin That Does Not Involve Metal Withholding

gla_public-private partnerships

The Advantage of Public-Private Partnerships to Accelerate Progress for Patients

GLA’s CEO Scott Santarella shares his insight on how scientific advancements that benefit patients can be accelerated through public-private partnerships, as he witnessed during his previous work in cancer research, and see now with both COVID-19 and Lyme disease.


by Scott Santarella, CEO, Global Lyme Alliance

As the scientific community focuses on unlocking the mysteries of COVID-19, Global Lyme Alliance (GLA) continues to vigilantly pursue its mission to conquer Lyme and other tick-borne diseases. While we know this will not happen overnight, the coronavirus pandemic is reinforcing GLA’s long-held belief that working through public-private partnerships (PPPs) is essential if we are to accelerate improvements in Lyme diagnostics and treatments.

With COVID-19, we’ve seen a global research collaboration unlike any in history. Biopharmaceutical companies are combining their resources and expertise with federal, state, and local governments, industry, academia, and philanthropies. Exceptional science is being done around the world with more than 160 new drug and vaccine candidates already in development. The unprecedented level of collaboration and investment is advancing coronavirus research at a breakneck speed. One could only imagine the impact we could have if we took this approach with all of our most challenging diseases and healthcare needs.

Although the novel coronavirus is now foremost, there is another serious pandemic that has been around for far longer and continues to rage. Some 427,000 people in the U.S. are newly infected with Lyme every year. One tick bite can change an individual’s life forever, from causing ongoing physical symptoms to persistent life-altering disorders. Up to 20% of Lyme disease patients fail to recover after standard antibiotic treatment. In some cases, the illness can lead to death. Yet unlike COVID-19, there has been limited industry and government interest in Lyme disease research as compared to other similar infectious and immunocompromised conditions.

To accelerate innovation in improving Lyme diagnostics and standard of care, GLA believes that nonprofits must work collaboratively and in partnership with industry, research universities, R&D centers, as well as all levels of government. Such partnerships allow nonprofits and other public institutions to tap into the scientific expertise and funding resources of their partners to reach goals far more quickly than they could have on their own. One leading biotechnology company—Regeneron Pharmaceuticals, Inc—recently took that step by announcing it would collaborate with New York State’s Wadsworth Center Laboratory to advance the development of new prophylactics and treatments for Lyme patients.

GLA has long invested in public-private partnerships as part of its strategy to expedite finding answers and helping patients. We are working in partnership now with several biotechnology companies including Ionica Sciences, which is developing a highly sensitive Lyme diagnostic test and Manus Bio, Inc., which is creating an environmentally-friendly repellent that kills ticks in seconds. Our collective goal is to bridge the gap between research discoveries and their rapid translation into marketable products, which could have a profound impact not just on the lives of Lyme patients, but the collective global community.

We are also working with private partners to increase Lyme and tick-borne disease awareness. Without accurate diagnostics and proven treatment options, the need for tick bite prevention is key. GLA has joined forces with companies such as Ranger Ready Repellents and Ivy Oaks Analytics to promote prevention methods for families, summer campers, and the general public. Working together we have protected hundreds of thousands from tick bites and tick-borne illnesses.

While we are proud and supportive of these forward-thinking efforts, public-private partnerships are often misinterpreted or frowned upon in the nonprofit world—even though there are a multitude of examples that validate how beneficial they can be. Although institutions want the private sector dollars and research assistance, for some, the word “private” connotes private sector control. In the non-profit world, the reluctance stems from the stigma of being thought of as “selling out” or relinquishing ownership and/or the dreaded fear of conflicts of interest.

The truth is, with solid contractual agreements, such partnerships can be set up to make the most of a private sector’s resources while preserving the integrity of a non-profit’s mission. A shared vision and a strong working relationship are essential in laying the foundation for a mutually beneficial partnership. GLA believes strongly that we must harness the skills, knowledge, and especially the resources of private-sector players, now is the time. We are at a watershed moment in which research data and healthcare technology are converging in ways that can accelerate substantive change. Without private support, many projects that could improve the quality of life for patients will remain ideas vs. impactful change agents.

Although the unprecedented threat of COVID-19 is now foremost, myriad opportunities still exist for changing the paradigm of Lyme disease understanding, treatment, and management. By embracing forward-looking public-private partnerships great progress and advancements can and will be made.

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Lyme Disease Research Remains Active During Pandemic

GLA-funded researchers are still focused on their Lyme disease research initiatives


by Mayla Hsu, Ph.D., Director of Research and Science, GLA

During this period of quarantines and social distancing, it is important to remember that while many labs are not running at full capacity, research into Lyme and other tick-borne diseases continues. Here’s a quick peek at what some of Global Lyme Alliance’s research partners have been working on during the COVID-19 quarantine.

Lyme and tick-borne diseases are bacterial infections, and this makes some work in this area exempt from the restrictions that have stopped other kinds of lab work completely. It turns out this is also a great time to catch up with study collaborators and other tasks that are sometimes given less attention when the focus is primarily on experimentation.

Nicole Baumgarth, D.V.M., Ph.D., an immunologist at the University of California-Davis, told us about her mice who have long-term infections of Borrelia burgdorferi, the bacteria that cause Lyme disease. Caring for them must continue even under social distancing constraints, and thankfully, continuing these studies means valuable data sets won’t be lost. Dr. Baumgarth also notes that “research continues, as does the teaching and training of our students…The work continues remotely at much the same pace as before—sometimes, I feel, even more so! This includes analyzing data, generating summary graphs, reading published papers and writing research manuscripts.”

For Dr. Michael Eriksen Benros, a psychiatrist at Copenhagen University Hospital in Denmark, the COVID-19 crisis brings patients whom he sees mostly via teleconferences. With his research, he says, “science does go on, luckily,” and he has been busy with revising publications, updating ethics and study protocols, and using time to reflect on the work and pursue new ideas. He recently received some funding to start a new study on the neurological and psychiatric complications in response to COVID-19, and will be using the same unique Danish nationwide health registries that he’s been using to study the links between Lyme disease and mental illness. This strategy taps into the information collected from a large population and can be applied to answer questions in both diseases. And because the health data is collected on a cradle-to-grave basis, it offers the possibility of studying lifelong disease outcomes.

Basic science studies in Lyme disease and bacterial genetics are also continuing apace. Klemen Strle, Ph.D., of the New York State Department of Health, points out that, “Although some of my time has been committed to COVID-19 related efforts, the majority of it remains focused on Lyme disease. Since much of the work these days involves collaborations, often with researchers at different institutions, working remotely has had less of an impact on this aspect of the work than I anticipated.” Dr. Strle has been presenting his work in online seminars and discussing new projects with collaborators. Much of this work is in preparation for projects that will start soon, as tick-borne disease season begins.

Dr. Lise Nigrovic, a pediatrician at Boston Children’s Hospital, directs the Pedi Lyme Net, a GLA-funded network of emergency room pediatricians in seven states. The network collects biospecimens from suspected tick-borne disease patients. These specimens will be used to develop new diagnostics and to understand Lyme and other co-infecting pathogens in children. Dr. Nigrovic says that while “COVID-19 has caused a temporary cessation of research, both basic and clinical … the Pedi Lyme Net site’s principal investigators are on the front lines in caring for children in the emergency departments.  However, Pedi Lyme Net research teams are still hard at work completing data entry, patient follow-up and biobank organization. Using already collected patient data, we are completing planned analyses and drafting manuscripts to share our findings.”

One task that many GLA-funded investigators are engaged in is publication writing, a vital part of the research process. As described in a previous blog, having research findings accepted and published in peer-reviewed scientific journals is essential in getting those new advances disseminated and read within the wider research community. Publishing, thus, advances our understanding of Lyme and tick-borne diseases, and fuels new ideas about treatment. So, a positive aspect of this quarantine period is that GLA-funded researchers will soon have their manuscripts ready for publication. In the coming year, we anticipate many new articles sharing exciting new findings and spurring even more scientific creativity.

Learn More About GLA Research Initiatives

GLA Scientific Advisory Board
Lyme Disease Research Report: Looking Back, Moving Forward
Published Research Findings
2019 Grantees
Postdoctoral Fellowships

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Research POV: Lyme Arthritis and Peptidoglycan

Important study identifies the Borrelia burgdorferi peptidoglycan as an immunogen likely to cause Lyme arthritis in some patients


by Mayla Hsu, Ph.D., Director of Research and Science, GLA

A longstanding mystery in Lyme disease is why some antibiotic-treated patients continue to suffer long-term symptoms, while others recover. It is possible that a hyperactive immune system in some patients causes inflammation-related tissue damage. Another possibility is that the bacteria, Borrelia burgdorferi, may still be alive in compartments of the body that are not readily accessible to antibiotics, and the bacteria’s continued replication causes ongoing symptoms.

A recent article found that a component of the bacterial cell wall, peptidoglycan (PG), might be driving the persistent inflammation that causes Lyme arthritis even after antibiotic treatment. The authors, who include a GLA-funded researcher, found B. burgdorferi PG antibodies in the synovial fluid that surrounds the knees of Lyme arthritis patients, which is evidence of an ongoing immune response against bacteria or fragments of its cell wall. In contrast, they did not find significant antibodies against PGs of any other bacteria. A strength of this study is that they compared synovial fluid from Lyme arthritis patients with that of other types of non Lyme-related arthritis. Only Lyme arthritis patients had synovial fluid B. burgdorferi PG antibodies.

Blood was also collected from the same Lyme patients whose synovial fluid was studied. Here, they found that sera (serums) of Lyme arthritis patients also had PG antibodies, although the levels were much lower than in the synovial fluid. Moreover, Lyme arthritis patient sera had much higher levels of PG antibodies than any detected in control patient sera. These findings indicate a continued immune response against PG, particularly in the synovial joints, specifically against B. burgdorferi.

Another asset of this study was its analysis of patient samples both before and after antibiotic treatment. The authors designed a way to detect PG itself, not only antibodies, in synovial fluid and sera. Using this test, they could not find PG in control synovial fluid, nor in Lyme arthritis patient sera. However, it was present in 92% of Lyme arthritis synovial fluids, both before and after treatment with antibiotics; and this was true of patients who had been treated with oral as well as intravenous antibiotics. In addition, the amount of PG strongly correlated with the level of PG antibodies in the same synovial fluid samples. This finding suggests that the bacterial cell wall itself is present in the synovia of patients, and that its presence elicits antibodies against PG.

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Comparison of B. burgdorferi PG antibodies for serum and synovial fluid, from Lyme arthritis patients (red) and from controls (black) (healthy and non-Lyme arthritis)

Do these results mean that B. burgdorferi is actively replicating in the patients in whom PG or PG antibodies were found? Testing for bacterial DNA was done on synovial fluid and blood, both before and after antibiotic treatment. Although both compartments were often positive for bacterial DNA before therapy, almost all samples became negative after therapy. This finding suggests that PG and PG antibodies persisted even after eliminating actively replicating B. burgdorferi at these sites, but it does not rule out bacterial replication elsewhere, and leaves open the question of how bacterial cell wall components could remain long after the bacterial DNA is no longer detectable.

This study also identified proinflammatory cytokines in synovial fluid, which play an important role in mediating immune responses. In vitro, the addition of purified B. burgdorferi PG to cultured peripheral blood mononuclear cells (PBMCs) caused increased levels of inflammatory cytokines like TNFα, IL1α, and IFNγ. These and others were also significantly elevated in the synovial fluid of Lyme arthritis patients, suggesting a possible mechanistic link between PG and inflammation. Finally, injection of purified PG in mice resulted in ankle swelling and inflammatory changes that are consistent with the established mouse model for Lyme arthritis.

In sum, these results make a strong case that B. burgdorferi PG may be responsible for driving inflammation and continued symptoms in post-antibiotic Lyme arthritis. Whether it is also implicated in promoting other long-term symptoms remains to be seen. These findings open up a new avenue of inquiry that may yield fruitful insights that will help us to better understand and care for people suffering from persistent symptoms.

Learn more about GLA’s research initiatives and accomplishments:

Research Report
Published Research Findings
Current Grantees 
First Observational Study for Lyme Disease Treatment
Post-treatment Lyme: Two Million by 2020
Blog: Why Good Science is Crucial

why is lyme so hard to treat_gla blog

Why Is Lyme Disease So Hard to Treat?

For many Lyme disease patients, the bacteria seem to outsmart antibiotic treatment. Why?


It’s a hotly debated topic, and one that is still not completely understood – what causes the persistent symptoms in many Lyme disease patients?  Why is it that 10-20% of patients, after early diagnosis and treatment with antibiotics, continue to face long-term, chronic, even debilitating, symptoms including joint or muscular pain, fatigue, and/or neurocognitive problems? And why do patients diagnosed later in their disease often have a more difficult time finding an effective treatment? Key possible culprits, persister bacteria, are under investigation, and researchers are uncovering their fascinating and diverse array of adaptive abilities, with the goal of one day eradicating them and more effectively helping patients.

Lying in Wait

Borrelia burgdorferi, the spirochete bacteria that cause Lyme disease, have an elaborate lifecycle, critical for their own day-to-day survival. They have evolved adaptations to multiple, sometimes harsh, environments – moving from bloodmeal-source host animals to ticks, repeating the cycle back into host animals, and sometimes into humans. Persistence is an essential and multi-faceted strategy that B. burgdorferi and other bacteria use to survive and adapt to their highly varied environments.

Unfortunately, these same adaptive abilities may also provide B. burgdorferi the ability to survive an onslaught of antibiotics. In vitro (in culture), treatment with antibiotics kills off most cells, but a small number survive because they adapt to have a new superpower – they are tolerant (although not resistant) to an aggressive antibiotic challenge. Their strategy is to lie dormant during an onslaught of antibiotics, changing their protein composition and shape. When the conditions are just right, and the antibiotics are cleared from the host’s system, they can then transform back into mobile spirochete form (thus giving them the freedom to resurge and multiply). GLA-funded research by Kim Lewis and his team at Northeastern University as well as research by GLA-funded Ying Zhang and his group at Johns Hopkins University revealed this amazing strategy. Their teams independently confirmed the existence in culture of dormant, persister B. burgdorferi, providing evidence that these persisters arise during antibiotic treatment and transform back into mobile spirochetes post-treatment. Whether this phenomenon occurs in patients remains to be shown, but it suggests a way to explain why antibiotic treatment is inadequate in a sizeable proportion of patients.

Interestingly, persistence is not unique to B. burgdorferi. The bacteria that cause other chronic diseases (e.g., tuberculosis, syphilis and leprosy) also form persisters.

A Master of Disguise

How do persisters survive harsh conditions such as antibiotic treatment? For one, they have an altered gene expression profile, producing key proteins which allow them to live in the presence of antibiotics. Throughout its life cycle, B. burgdorferi is a master chameleon, transforming itself from its corkscrew-shaped spirochete form into a variety of shapes, such as round (metacyclic), L-form bacteria, spore-like granules or cysts, and then back again into spirochetes. These different forms can impact diagnosis. For example, there is some limited evidence that B. burgdorferi takes on L-forms in spinal fluid, which could impact methods used for screening when a case of neuroborreliosis (a neurological manifestation of Lyme disease) is suspected, for example.

Borrelia bacteria in the blood
Borrelia bacteria in the blood

B. burgdorferi, similarly to other bacteria, may also transform itself into biofilms, which are a complex aggregate of bacteria with a protective slimy mucus layer surrounding it. Studies by Kim Lewis provided evidence of biofilms contributing to persistence in other diseases, such as Cystic Fibrosis and oral thrush. However, there is only minimal in vitro evidence in the case of B. burgdorferi, which is limited in usefulness until more research is done, and further studies will illuminate whether biofilm forms of B. burgdorferi exist in patients.

Yet another strategy used by the wily B. burgdorferi and other bacteria is to invade host cells. For example, the bacterium that causes tuberculosis (TB), Mycobacterium tuberculosis, can exist in a dormant persister state in TB lesions, which necessitates much longer antibiotic treatment in patients than is seen in vitro. Some preliminary findings suggested that in cultured neurons, glial cells, macrophages, and skin keratinocytes, atypical and cystic B. burgdorferi have been found.

Promising Research

Researchers have had very limited success in cultivating replicating B. burgdorferi directly from animals or humans post-antibiotic treatment, which is part of the difficulty in doing experiments on persisters. There is some indirect evidence of persisters from multiple studies in animals (mice, dogs, monkeys) infected with B. burgdorferi and treated with antibiotics. For example, using a mouse model of Lyme disease, after one month of antibiotic treatment, researchers isolated B. burgdorferi DNA and detected non-dividing but infectious spirochetes.

Researchers have also been able to isolate live B. burgdorferi from animals using xenodiagnostic ticks’, in which uninfected ticks feed from an infected animal or human and become infected after feeding. This offers proof that the host was infected with B. burgdorferi. In a study with infected animals who exhibited a clear resurgence of bacteria following antibiotic treatment, B. burgdorferi was then isolated using xenodiagnostic ticks, a strong indication that these are persisters.

When B. burgdorferi-infected nonhuman primates were treated with antibiotics, bacteria were also recovered from multiple tissues, suggesting that bacteria could survive. Signs of inflammation in and around these tissues were also observed.

In an exciting 2019 study, Ying Zhang and team isolated slow-growth forms of B. burgdorferi (including biofilm-like, round body and spirochetes) from culture and compared mice inoculated with these slow-growing forms versus mice inoculated with fast-growing spirochetal B. burgdorferi. The slow-growth persister B. burgdorferi were not only more tolerant to the standard Lyme disease antibiotic treatment with doxycycline or ceftriaxone but they were also associated with more severe arthritis in mice than the fast-growing spirochete form. However, a cocktail of antibiotics – Daptomycin, Doxycycline and Ceftriaxone – did successfully eradicate the infection in the mice infected with slow-growing persisters. Human studies modeled after these would be helpful in understanding the disease course, especially the response to antibiotics.

In other studies, different cocktails of antibiotics, as well as essential oils, have been successful in eradicating B. burgdorferi in vitro. Disulfiram, a drug used for treating alcoholism, has been shown to be extremely effective in eradicating many forms of B. burgdorferi in vitro and in mice, and in a small study in humans.

Despite all these promising results in culture and in animals, trials in humans have not advanced well. Based on research done to date, researchers cannot confirm or exclude that live persisters are present in antibiotic-treated patients who have persistent symptoms (i.e., patients with post-treatment Lyme disease symptoms). One large part of the problem is the shortage of confirmed Lyme disease patients for clinical trials, as many patients lack concrete clinical (serological) evidence of having Lyme disease. In three separate clinical trials, only 4% of 5457 patients made it through the screening process to enter a trial.

Altogether, some critical groundwork has been established in the study of persisters.  However, studies surrounding persisters are still in early stages, and their connection to ongoing symptoms of post-treatment Lyme and chronic Lyme still warrant more confirmation and extended studies. There is a great need for evidence-based research conducted at all levels of research involving persisters, from in vitro studies through clinical trials. Supporting these efforts calls for improved diagnostics and detection methods for persisters, and an incremental move into larger-scale human studies which confirm the presence of live persisters and explore treatment options. GLA is optimistic that with future studies, there will be new breakthroughs in this very important area.

By Global Lyme Alliance and Dana Barberio, M.S., Scientific/Medical Writer and Principal, Edge Bioscience Communications


Learn more about GLA’s research initiatives and accomplishments:

Research Report
Published Research Findings
Current Grantees 
First Observational Study for Lyme Disease Treatment
Post-treatment Lyme: Two Million by 2020
Blog: Why Good Science is Crucial

ashley groshong_research scientist

The Making of a Lyme Disease Research Scientist

Most Lyme disease stories start with a tick bite and symptoms. But Ashley Groshong’s (pictured) Lyme disease odyssey began by peering down a microscope lens. As a young biology student at the University of Arkansas, she studied Bacillus bacteria, which include the pathogen that causes anthrax. However, it wasn’t until she began a training rotation in a lab studying Borrelia, the spirochete bacteria that cause Lyme disease, that she became enthralled. “Literally from the first time I saw those guys in a microscope, I was in love. It only made it more fascinating that they were so hard to work with. They are so odd, they don’t do anything that is standard to microbiology textbooks.”

Years later, after receiving her Ph.D., Dr. Groshong’s “love” story endures. She is now junior faculty at the University of Connecticut, continuing to work on Lyme disease. She has made important discoveries in understanding how the bacteria grow and cause illness. We in the Lyme community are grateful that someone so dedicated is in our corner, looking for better ways to understand the bacteria, and ultimately to treat patients. But in the last 40 years, the standard of Lyme disease care hasn’t changed much. Today almost 2 million people in the US are estimated to suffer long-term, post-treatment Lyme disease. Why has progress been so slow?

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Ashley Groshong in the UCONN Health Spirochete Lab/OVPR Photo

One answer is that there aren’t enough Dr. Groshongs out there. The road to becoming a qualified expert is a long and rigorous one. Typically, it begins with science majors in universities and colleges. Those who are interested in further study continue with graduate work, which requires a research-intensive, usually lab-based project that can last 3-7 years and leads to a Ph.D.

Newly-minted Ph.D. scientists then spend an additional 3-5 years as postdoctoral fellows, working under the mentorship of established scientists. Often, the projects they develop open areas of inquiry that they subsequently use to set up their own, independent labs.

Driving all of this training is funding. The National Institutes of Health (NIH), the major U.S. government agency funding biomedical research, has an annual budget of $32 billion. Typically, academic research grants can be applied for through its NIH extramural funding program. This money is dedicated to basic science, or understanding disease and disability. Findings pave the way to improved prevention and treatment of illness, and have led to life-saving cures and vaccines.

The NIH also pays for studentships and postdoctoral fellowships. These are awards that pay for salaries, tuition and other education expenses so that trainees can focus all their time on learning. Such critical funding at these early career stages helps to keep young scientists on track.

Sadly, Lyme disease continues to be a poorly-funded area of research. With a limited pool of trained personnel, there is always the risk that Ph.D. students and postdoctoral scientists will leave to work in better-funded subject areas. Since provocative research is often driven by young scientists doing curiosity-driven basic science, this attrition contributes to the slow pace of discovery in the Lyme field.

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Deborah Blackman, third from right, with the first class of “Blackman-GLA Postdoctoral Fellowship” recipients

That’s why postdoctoral fellowships are such a tremendous boon to Lyme research. The Blackman-GLA Postdoctoral Fellowship program began in 2017, with the generous support of the Blackman family. It was conceived as a serious commitment to developing young Lyme scientists at a vulnerable stage in their career training, for which support is often lacking. Ashley Groshong, a postdoctoral fellow at the time, was one of five grantees. They all had to write a detailed description of their research projects and plans for how to address the subject of bacterial persistence and host evasion. They also had to show previous research achievements and describe the project milestones they anticipated; moreover, they had to prepare a three-year project budget. The award also included a travel allowance, so the grantees could meet and collaborate with other Lyme researchers.

Awards of three years length are particularly helpful, because such stable support keeps scientists from constantly interrupting their lab work to write funding applications. Because their research projects have defined goals, publication in peer-reviewed journals is anticipated. This, in turn, positions the postdoctoral fellows to develop new skills as they transition into the next step — becoming independent scientists.

A measure of Dr. Groshong’s success is that she was recently promoted to her junior faculty position. Collectively, the Blackman fellows have published four peer-reviewed research articles so far, a stellar accomplishment for a program that hasn’t finished its three years of funding. When finishing their postdoctoral training, a major goal for academia-bound scientists is to obtain an R01 grant from NIH. For many university departments, faculty appointments are in large part dependent on such grants, which are a significant source of support for sustaining an independent research program.

However, the age at which investigators are awarded their first R01 grant has steadily increased. From 1980 to 2012, the average age of a first R01 grant recipient grew from age 35 to 44. Commensurately, the success rate of R01 applications has dropped from close to 40% to less than 20%. Waiting until one’s mid-forties to achieve this key career goal means many leave research for industry or non-research careers. This uncertainty is another reason Lyme disease research support at all levels has become reliant on nonprofits like GLA. Moreover, it underscores the importance of privately funded postdoctoral fellowships.

GLA is proud to partner with the Blackman family to develop the pipeline of Lyme scientists. As Ashley Groshong says, “the fellowship has given me the opportunity to really make this project into my own work and get it to a point to move on to NIH grants. That makes me very competitive as I look for academic jobs. I love teaching and training the next generation of scientists. I can’t imagine being fulfilled doing anything else.”

by Mayla Hsu, Ph.D., Director of Research and Science, GLA

Please contact [email protected] should you be interested in helping to foster additional postdoctoral researchers to accelerate advances in understanding and treating Lyme disease and tick-borne co-infections. We also encourage you to contact your elected representatives in Washington and urge them to advocate additional NIH postdoctoral funding for Lyme disease and other tick-borne co-infections.

why good science is crucial

Why Good Science is Crucial

While the road to drug discovery and new treatment options for Lyme disease may seem slow, it’s imperative that the science is sound.


Lyme disease patients all know the thrill of hearing through the grapevine about a new remedy for chronic Lyme disease symptoms or a new diagnostic test. Often by word-of-mouth or through patient forums, a patient will hear that someone’s symptoms improved after taking an exciting new treatment. A savvy patient may then do a Google search on this new treatment option, perhaps discovering a few websites discussing the treatment, sometimes even finding a scientific research article that supports the other patient’s claim. Fantastic news, let’s talk to our doctor about it, or start our own regimen of treatment, if we can take something over-the-counter. Why not?

In actuality, this approach is not the best one, for many reasons. For one, the other patient may be taking a slew of other treatments, or be in a different stage of Lyme disease. Also, this may be a one-off or temporary result for this one patient, with most patients not responding to the same treatment. But what if you found results in a scientific journal that support the claim? Those results, if the studies were conducted in animals, may not be at a suitable dose or useful at all in humans, and perhaps even harmful.

While the road to new diagnostics and new treatment options for chronic Lyme disease symptoms and other illnesses may seem unreasonably sluggish, the science behind the diagnostics and treatments must be solid, and often that translates into a long process, but one that results in more successful treatments. To appreciate this at a deeper level, let’s step into what’s needed for good scientific research, and why clinicians and patients benefit from this process.

The gold standard for reporting scientific information is the peer-reviewed journal article, which is the cornerstone for high quality scientific research, and the best avenue for presenting information to the scientific community. These articles undergo a rigorous process in which other research specialists in the same field provide feedback, which the authors need to address by modifying their written content or experimental studies, or face rejection. For example, the researchers may need to return to the bench and add in some better controls, or even add in a whole new experiment before publishing. This powerful review process drives the most significant science because holes or weaknesses in the science are identified and can be weeded out before going to the next phase of research. Another perk is that these articles are a fantastic resource for organizations like NIH or GLA when they are deliberating over the most promising projects to fund. This iterative process of inquiry and criticism by knowledgeable specialists’ fuels quality and is necessary to achieve the most meaningful therapeutic, diagnostic or medical device.

The drug discovery process is designed like a funnel, or pyramid, with a large amount of basic research at the outset, only some of which progresses into more applied research, culminating in a clinically useful therapeutic or diagnostic. Basic research has no immediate obvious application. Rather, it explains how things work, e.g., researchers have observed some limited evidence that Lyme disease bacteria, Borrelia burgdorferi, take on different forms besides that of spirochetes, which could theoretically protect the bacteria from antibiotic treatment. Often basic research starts by observing results in vitro (in a petri dish or in culture). Clinical research applies findings from basic research. It tests what interventions or medicines might be useful in improving treatments e.g., testing a therapeutic that works well against one of these alternative forms of B. burgdorferi. In clinical trials for a medical intervention, researchers start with preclinical studies on animals, then move into humans if they are successful. An in vivo preclinical study or series of studies on a novel therapeutic for Lyme disease might involve infecting mice with B. burgdorferi, observing and quantifying alternative bacterial forms, treating the mice, and looking at results.

GLA_drug discovery process_funnel

The next step after preclinical studies, if they are successful, is to then move into human clinical trials. These human studies involve small trials to address preliminary questions such as safety and side effects (Phase I trials), and then gradually progress to larger trials involving more patients and an evaluation of efficacy (Phase III-IV). These trials might evaluate if patients reach a defined endpoint for efficacy after being treated with the novel therapeutic, such as a defined reduction in Lyme disease symptoms. Only if the intervention makes it through all of these stages does it get the opportunity to be reviewed, and possibly approved by the FDA (if U.S. based) for use in humans. Similarly to clinical research, translational research builds on basic research to create new therapies, medical procedures, or diagnostics, and moves the science from bench to bedside. This sometimes involves a multidisciplinary effort. For example, a fantastic way to implement the newly approved therapeutic would be to create a companion diagnostic that detects alternative forms of B. burgdorferi, thus screening for patients that would be suitable candidates for the novel treatment.

All of this research is generally very expensive to carry out. Large pharmaceutical and biotech companies will sometimes have their own pot of money to support some or all of these phases of development. In many cases, however, companies and academic organizations are highly dependent on grant money funded by the government or non-profits such as GLA. Early seed money from research grants investigates good ideas. If data is promising, researchers can apply for further funding for small scale grants for pilot studies, in which they can flesh out their ideas with more samples, more controls, and perhaps start evaluating the mechanism of action. Full-scale grants are provided for fully-realized studies, which involve proper controls, delineated milestones, building on previous work and data, and further mechanism of action studies. The NIH should be funding all levels of this research for Lyme and tick-borne diseases, but unfortunately, its support is not commensurate with case numbers.

Another embedded factor to implement high level research is the lengthy time and considerable cost in educating and training skilled researchers, involving training scholarships and fellowships. The traditional academic path requires a researcher to have a BS/BA, followed by a Ph.D. and a postdoc fellow position. The researcher then may go on to hold a junior faculty/early career investigator position and then may become an Assistant/Associate/Full Professor who leads an independent lab. Even entering pharmaceutical/biotech companies as a Ph.D.-level scientist sometimes requires postdoc fellow training, as competition is high for these positions. Supporting development of people on this pathway would keep them in the Lyme and tick-borne disease research community instead of losing them to areas of greater funding.

Yet another boon to fostering research, but adding to the expense, is the Lyme disease and tick-borne disease research community conferences, seminars etc. that help to foster networking, collaboration, and exchange of reagents and ideas.

This culture of inquiry, collaboration and constructive feedback is inherent and necessary for scientific discovery and application, and in the long run may produce top-notch therapeutics, diagnostics and treatments for patients, making it all worth the wait.


By Global Lyme Alliance and Dana Barberio, M.S.


Learn more about GLA’s research initiatives and accomplishments:
2018 Research Report
Published Research Findings
Current Grantees 
First Observational Study for Lyme Disease Treatment

lyme disease expert

Leading Lyme Disease Expert Weighs in on New Study Showing Public Health Crisis

Guest Point of View: John Aucott, M.D., Director of the Johns Hopkins Lyme Disease Clinical Research Center; Associate Professor of Medicine, Johns Hopkins University School of Medicine


In a recently published study, the authors* estimate the cumulative number of post-treatment Lyme disease (PTLD) cases in the United States in both 2016 and 2020. This is important because it represents the first time that researchers have attempted to estimate a downstream effect of infection with Borrelia burgdorferi; the number of people living with PTLD. Their results suggest that the predicted prevalence of PTLD by the year 2020 could be as high as 1,944,189, depending on the assumptions used.

The magnitude of this result points out the major public health impact of the unchecked tick-borne disease epidemic.

It has long been challenging for researchers to estimate the number of new cases of Lyme disease, let alone the rate of PTLD. A number of assumptions and estimations need to be made to generate a mathematical model with as much accuracy as possible. Therefore, the underlying assumptions used in this paper are extremely important, as they directly determine the results. This is illustrated by the wide range of predicted cases for 2020; estimated cases range from 81,509 to 1,944,189 cases, over a 20-fold difference. The first key assumption needed to create the model is the number of new cases of Lyme disease each year (i.e. the incidence). Data reported to the CDC on the yearly incidence of Lyme disease are widely assumed to be under-reported due to passive surveillance methods. Estimates derived from laboratory testing and health claims records all point to an annual incidence in the hundreds of thousands of cases a year. Furthermore, it is difficult to precisely estimate how this rate may change over time due to a range of factors such as climate change, seasonal variation, expansion of the tick vector, and/or increased public awareness of the disease. The authors included three different scenarios to account for this variability.

A more difficult assumption to pinpoint mathematically for inclusion into the model is the rate used for estimating the percentage of patients who develop chronic illness after receiving standard antibiotic treatment, partial treatment, or no intentional antibiotic treatment of Lyme disease. In prospective studies of both early Lyme disease and late Lyme arthritis the percentage of patients who experience ongoing symptoms after antibiotic therapy is approximately 10%. The 10% rate in these studies among ideally diagnosed and treated patients may underestimate the rates found in the community practice of medicine, where delayed diagnosis and imperfect and delayed treatment may be more common. The rate may also be higher in early disseminated Lyme disease with neurologic involvement, which has not been studied extensively in North America, and thus may be under-represented in estimates of PTLD. The authors incorporated two different PTLD rates (10% and 20%) to account for the uncertainty in this estimation.

There are additional assumptions that may have been important to add to the model. First, this study does not account for patients who recover from PTLD over time and no longer suffer from the disease. In the current model, survival and death rates, but not recovery, are accounted for as long-term events. Second, there is no attempt to include different PTLD risk percentages for children who, some have suggested, may have a lower rate of PTLD compared to adults. The absence of these different rates in the model may lead to an over estimation of the number of cases of PTLD.

These limitations should not detract from the importance and relevance of this novel research. The fact that the number of cases of chronic illness related to Lyme disease, as estimated by published rates of PTLD, is so high is extremely important.

These numbers are on par with other important public health threats such as HIV. When combined with the recognized severity of PTLD for patients, the impact is even more significant.

Another important result of this study is the estimated future age distribution of PTLD cases. As the US population ages, the impact of PTLD on older Americans with other co-existing, chronic, conditions may become an important, unrecognized, public health issue. It is unknown how PTLD may interact with or alter the progression of common conditions such as dementia. It will be extremely difficult to tease out the role of prior Lyme disease as a cause or an aggravating factor without molecular markers of central nervous system infection and/or ongoing inflammation in the setting of PTLD.

In conclusion, this study is extremely relevant in understanding the important public health significance of chronic illness related to Lyme disease.

The methodologies used and the magnitude of the findings should inform future epidemiologic studies of disease risk and population-level impact. As research in Lyme and other tick-borne diseases advances and more exact estimates of the model assumptions used in this paper are generated, it will be important for future studies to revisit these calculations, as well as strive to estimate the long-term impact of other tick-borne diseases, including Babesia microti and Borrelia miyamotoi. Finally, this paper should serve as another wake up call to leaders in the public health, medicine, and policy arenas regarding the impact of the expanding tick-borne disease epidemic.

Click here to access published study.
Click here to access GLA press release.

*About study authors: Allison DeLong, M.S., a biostatistician at Brown University’s Center for Statistical Sciences and a member of GLA’s Scientific Advisory Board; Mayla Hsu, Ph.D., Director of Research and Science at GLA; Harriet Kotsoris, M.D. former CSO, GLA


john aucottOpinions expressed by contributors are their own.

John Aucott, M.D., is Director of the Johns Hopkins Lyme Disease Clinical Research Center; Associate Professor of Medicine, Johns Hopkins University School of Medicine. Learn more at https://www.hopkinslyme.org/ 

Dr. Aucott is a GLA research grantee, and co-director of the landmark Study of Lyme Immunological and Clinical Events (SLICE) Study that has defined many parameters of acute and long-term Lyme disease.



GLA Note: About the term “PTLD”: The term post-treatment Lyme disease syndrome (PTLDS) refers specifically to the 10-20% of patients who were diagnosed and treated at the acute stage of their Lyme infection, yet continue to remain sick and symptomatic. Using this term is not intended to exclude anyone suffering from long-term or persistent infection. In context for this research project, it’s critical to start with a well-defined group, such as PTLDS, for study validation purposes. Due to the inaccuracies in Lyme diagnostic testing, at all stages of the disease, it’s nearly impossible to determine the entire population at this point in time. We fully acknowledge that there are more Lyme sufferers outside of the “PTLDS” category, and it’s our goal to find the answers that will help all these patients. The positive outcome of this study is that we now have a starting point to share with the medical and general communities about the substantial number of people who are suffering in the U.S. as a result of Lyme disease.

borrelia burgdorferi_mice

GLA POV: Ability of Stationary Phase Persister/Biofilm Microcolonies of Borrelia burgdorferi to Cause More Severe Disease

by Timothy Sellati, Ph.D., Chief Scientific Officer, GLA

Ying Zhang, Ph.D., a Global Lyme Alliance (GLA)-funded investigator, and his team at Johns Hopkins University just published a seminal study in the journal Discovery Medicine titled “Stationary phase persister/biofilm microcolony of Borrelia burgdorferi causes more severe disease in a mouse model of Lyme arthritis: Implications for understanding persistence, post-treatment Lyme disease syndrome (PTLDS), and treatment failure”.

Lyme disease patients, infected via tick bite with the bacterial spirochete B. burgdorferi, are routinely treated with two to four weeks of Doxycycline, Amoxicillin, or Cefuroxime, which is curative in many cases if treated at the onset of the infection. However, research shows that despite treatment, up to 20% of patients continue to suffer lingering symptoms of fatigue, pain, or joint and muscle aches, and neurocognitive manifestations that last 6 months or more.  This clinically-defined condition is known as post-treatment Lyme disease syndrome (PTLDS).  A long-standing mystery is whether development of PTLDS reflects 1) persistence of B. burgdorferi in a patient’s tissues, consistent with chronic infection, or 2) self-perpetuating inflammation caused by tissue damage triggered by the original infectious insult.

Zhang and colleagues published several influential papers over the past five years revealing a potential answer to this mystery. His lab showed that in vitro stationary phase (non-growing) cultures of B. burgdorferi contain different morphological variants. These bacterial variants include planktonic (free-swimming) spirochetal forms, round body forms, and aggregated microcolony (biofilm-like) forms, which have varying levels of persistence (e.g., the capacity to tolerate antibiotic exposure) in comparison to the log phase culture, which mainly consists of rapidly growing spirochetal forms with no or few persisters. B. burgdorferi develops into these morphological variants under stress conditions but their relevance to severe and persistent Lyme disease was unclear until the publication of this new study.

Zhang et al. report that biofilm-like microcolony (MC) and planktonic (free-swimming spirochete and round body; SP) variants found in stationary phase cultures were not only more tolerant of exposure to antibiotics but also caused more severe arthritis in mice than the log phase spirochetes (LOG). Importantly, the authors show that the murine infection caused by LOG could be eradicated by Ceftriaxone (CefT) whereas the persistent infection established with MC could not be eradicated by Doxycycline (Doxy), CefT, or Vancomycin (Van), or Doxy+CefT or Van+CefT, but could only be eradicated by the persister drug combination Daptomycin (Dapto)+Doxy+CefT. This GLA-funded work establishes for the first time that varying levels of persistence and the severity of disease pathology caused by infection with B. burgdorferi is linked to different morphological forms of the spirochete.

The following facts highlight the importance of this novel discovery. The number of patients developing PTLDS, or chronic Lyme, which is less clinically well-defined, is on the rise; a trend that is consistent with the rise in annual incidence of Lyme disease, which is ~427,000 cases. The absence of a full understanding of the cause(s) of PTLDS hampers efforts to effectively treat patients suffering with this syndrome. The authors demonstrated that the degree of persistence or persistent infection varied with different inoculae, where biofilm-like microcolony inoculae produced a more severe and persistent disease that could not be eradicated by the current Lyme antibiotics or even some two-drug combinations but could be eradicated by the persister drug combination Dapto+Doxy+CefT. In contrast, the disease induced by the log phase spirochetal forms is more readily eradicated by CefT. That the inclusion of persister drug Dapto, in combination with Doxy and CefT, is critical for eradicating the persistent infection established by persister inoculae validates the relevance of Dr. Zhang’s GLA-funded efforts to screen for drugs or drug combinations against stationary phase bacteria enriched in persisters in vitro, which were published by Feng et al. in 2014 and 2015 (see influential papers here).

Finally, the reported findings may not only provide a new understanding of PTLDS and perhaps chronic Lyme disease, but also will inform and accelerate development and testing of novel persister drug combination regimens that can more effectively cure persistent Lyme disease in the future. GLA’s goal in the near future will be to support human clinical trials to evaluate if the persister drug combination could more effectively treat or cure patients with PTLDS/chronic Lyme disease.

Pictured: Image of joint histopathology taken from a mouse infected with micro-colony/biofilm-like B. burgdorferi. Read Dr. Zhang’s full paper here.

timothy sellatiTimothy J. Sellati, PH.D. is Chief Scientific Officer at Global Lyme Alliance

As GLA’s Chief Scientific Officer, Dr. Sellati leads GLA’s research initiatives to accelerate the development of more effective methods of diagnosis and treatment of Lyme and other tick-borne diseases.

GLA Lyme Disease Research Symposium 2019

GLA: Lyme Disease Research Symposium 2019



by Mayla Hsu, Ph.D., Director of Research and Science, GLA
(pictured: GLA grantee Dr. John Aucott, GLA’s Dr. Mayla Hsu, GLA SAB members Drs. Mark Soloski and Utpal Pal)

Earlier this month, Global Lyme Alliance held its 9th annual research symposium, with an invitation-only forum which welcomed scientists from its Scientific Advisory Board (SAB) and grantees. These researchers came from around the US and sought to contribute scientific guidance and perspective in identifying areas of future research opportunities.

GLA lyme disease research symposium 2019
GLA SAB member Dr. Mark Wooten, GLA CSO Dr. Timothy Sellati, GLA SAB member Dr. John Belisle, GLA grantee Dr. Catherine Brissette

As in previous years an exciting series of oral and poster presentations focused on patient diagnostics, particularly in the areas of direct detection of pathogens.  However, this year also featured informative exchanges about patient biomarkers and systems-oriented approaches such as metabolomics and comprehensive immunological profiling. Host genetics, bacterial genetic subtypes, microbiome, and the contribution of precision-oriented pathogenesis studies were also aired. The latter were aimed at answering the persistent question of why some patients are cured after initial treatment, while others continue to suffer for years. Diverse in scope, this research illustrates the breadth of science to which GLA is committed.

GLA grantee Dr. John Aucott, GLA’s Dr. Mayla Hsu, GLA grantee Dr. Lise Nigrovic, Dr. Sheila Arvikar

Many patients with long-term Lyme disease suffer from neuropsychiatric disorders, which are poorly understood. These patients and their diagnoses were discussed, with images from PET scans showing abnormal neurological inflammation and activity. Mechanistic studies of cognitive dysfunctions and neuroimmunology were also aired. Other exchanges included the basic science of antigen processing and presentation, during the initial stages of Borrelia infection, immune responses to Babesia, and dissections of the pathology caused by tick-borne pathogens at the genetic level.

GLA CSO Timothy Sellati, GLA grantee Dr. Ying Zhang, GLA Board Chairman Rob Kobre, GLA SAB member Dr. Armin Alaedini

An exciting series of talks were given by five young scientists, who are the recipients of the Mark and Deborah Blackman-GLA Postdoctoral Fellowships in bacterial persistence and host evasion. Their presentations covered a variety of subjects. For example, they identified Borrelia genes essential for bacterial replication and dissemination, metabolic changes during the cellular change to persister bacterial growth, and interactions with the host immune system. Their progress showed how support of young scientists during a formative time in their professional development is critical in the development of a pipeline of trained research professionals.

In sum, the symposium was an exchange of scientific ideas, camaraderie, and mentoring. High-level science was discussed in a collegial, relaxed setting. GLA thanks all researchers and SAB members for joining us, and we look forward to ongoing research findings.

impact lyme disease

Top 7 Science-Based Events to Impact Lyme Disease in 2018

GLA’s Chief Scientific Officer and Director of Research and Science identified the Top 7 science-based events to impact the Lyme disease community in 2018


Connection Between Lyme Disease and Depression

impact lyme diseaseGLA-funded investigator, Brian Fallon M.D., with Columbia University, published a study in the journal Psychosomatics linking Lyme disease and mental disorders, particularly depression and suicide. According to the study, titled “Depressive Symptoms and Suicidal Ideation Among Symptomatic Patients with a History of Lyme Disease vs Two Comparison Groups,” depression has been reported in 8 – 45% of patients with post-treatment Lyme disease syndrome (PTLDS), but little was known about suicidal tendencies in these patients. The extent and severity of depression and suicidality was compared between PTLDS and HIV/AIDS patients, and a non-patient control group was compared.

The results conclusively demonstrate that suicidal tendencies increase among patients who are depressed and that, perhaps surprisingly, depression experienced by PTLDS and HIV/AIDS patients was statistically indistinguishable. This seminal study highlights the fact that one in five patients with PTLDS reported suicidal thoughts and the importance of screening for depression and suicidality to optimize patient care. See more GLA-published research

Pathway Opened for Better Lyme Disease Diagnostic Tests

Inaccurate diagnostic testing is one of the biggest challenges for patients and physicians alike. Thanks to a report generated from a meeting of Lyme disease experts, including scientists from the FDA, NIH and CDC, the pathways for impactful superior diagnostic tests are here. The meeting, underwritten by GLA, resulted in two articles summarizing the experts’ findings; “Advances in Serodiagnostic Testing for Lyme Disease Are at Hand” and “Direct Diagnostic Tests for Lyme Disease” were published in Clinical Infectious Diseases, a journal of the Infectious Diseases Society of America.

The articles outline the need for better tests and describe newer approaches in direct detection that show promise and could help thousands of people with Lyme to get the treatment they need as early as possible after infection. Learn more 

Essential Oils Show Promise as Effective Treatment for Lyme Disease

Ying Zhang, Ph.D. of Johns Hopkins Bloomberg School Health, published exciting findings on the effectiveness of certain essential oils (EOs) to treat stationary phase and persister forms of Borrelia burgdorferi. This GLA-funded study identified 10 EOs that have strong activity against stationary phase burgdorferi at a low concentration of 0.1%; and found that of the 10 EOs, those of garlic, allspice, and Palmarosa were active at even at 0.05% concentration. This finding is particularly important because while the majority of the Lyme disease patients can be cured with 2 – 4 weeks antibiotic treatment, about 10 – 20% of patients continue to suffer from persistent symptoms. Use of EOs as an alternative treatment may be effective in this latter patient population. Studies have now advanced to the stage of testing the therapeutic effects of essential oils in B. burgdorferi-infected animal models, the results of which will lay the foundation for human Phase I/II clinical studies GLA will support. Learn more

Direct Link Between Lyme Disease and Arthritis

New findings show the correlation of Lyme disease-associated IgG4 autoantibodies with synovial pathology in antibiotic-refractory Lyme arthritis. Published just this month in the journal Arthritis and Rheumatology Allen Steere’s group has published that specific classes of antibody and cytokine profiles are unique to patients with antibiotic-refractory and -responsive Lyme arthritis. More importantly, this is the first study to definitively demonstrate that the level of antibodies capable of cross-reacting with Lyme disease-associated auto or self-antigens correlates with specific inflammatory symptoms in antibiotic-refractory Lyme patients.

Record Increase in Cases of Lyme and Vector-Borne Diseases in the U.S.

The CDC made two significant announcements this year. First, the annual number of Lyme disease cases has reached ~427,000, up from ~329,000. Second, combined tick, flea, and mosquito-borne diseases have tripled in the last 13 years. These announcements highlight the phenomenal increase in vector-borne diseases in the U.S. and the need for continued vigilance in protecting oneself against tick and insect bites. The CDC report also highlights the fact that an ever-expanding diversity of bacterial, viral, and parasitic vector-borne pathogens are being discovered through continued research efforts.

These findings suggest that the U.S. health agencies charged with protecting the public are tracking the increase and that these numbers are based on surveillance case reporting and not a clinical diagnosis, meaning the actual annual numbers of tick-borne disease cases is likely to be much higher.

The Impact of Climate Change on the Expanding Tick Population

Research confirms that the size and activity of tick populations are increasing and the geographic ranges of a variety of tick species are expanding. It is now commonly accepted, by the public and scientists that this is due in part to climate change. Mary Beth Pfeiffer’s book, “Lyme: The First Epidemic of Climate Change”, brought this to the forefront for many in 2018. Watch Q&A with Mary Beth Pfeiffer

Release of HHS TBDWG Report to Congress

The federal Tick-Borne Disease Working Group (TBDWG) issued its first report to Congress, confirming what Lyme disease patients and their caregivers have known for decades—that there is a “serious and growing threat” of tick-borne diseases throughout the nation, and that the government needs to invest more in research, prevention and treatment of these illnesses. Learn more 

List Compiled By

Timothy J. Sellati, Ph.D., Chief Scientific Officer, GLA
Mayla Hsu, Ph.D., Director of Research & Science, GLA

Learn More About GLA’s Research Initiatives

View Research Report or email [email protected] with any questions

catherine brissette_meet the researcher

Meet the Researcher: Catherine Brissette, Ph.D.


NAME: Catherine Brissette, Ph.D.
TITLE: Associate Professor, Biomedical Sciences
INSTITUTION: University of North Dakota

Catherine (Cat) Brissette received her B.S. degree in Zoology from Louisiana State University, her M.S. with Dr. Paula Fives-Taylor at the University of Vermont, and her Ph.D. from the University of Washington for her work with Dr. Sheila Lukehart on interactions of oral spirochetes with the gingival epithelium. She continued work with spirochetes as a postdoc with Dr. Brian Stevenson at the University of Kentucky, where she switched to the Lyme disease spirochete Borrelia burgdorferi. Her work with Dr. Stevenson involved studies of outer surface adhesions and regulation of virulence factors. Cat accepted a faculty position at the University of North Dakota in the Department of Microbiology and Immunology (now part of Biomedical Sciences), where she continues her work with pathogenic Borrelia species. Her lab is particularly interested in understanding why B. burgdorferi has a tropism for the central nervous system; that is, why the B.burgdorferi’s surface proteins interact with the hosts’ extracellular matrix, cells, and components of the immune system, and the regulatory mechanisms controlling the expression of these infection-associated proteins.

Dr. Brissette is also a member of GLA’s esteemed Scientific Advisory Board.

Drs. Eva Sapi, Ali Divan, Catherine Brissette, Janakiram Seshu, and Mayla Hsu, GLA’s Director of Research and Science, at GLA’s Lyme Disease Research Symposium 2017


CB: My Ph.D. work involved a different kind of spirochete (one involved in periodontal disease); the challenge of working with a different pathogen (the agent of Lyme disease) was exciting.


CB: We are working on several different aspects of neurological Lyme disease. More specifically, how the bacteria gets into the central nervous system in the first place, how the immune system responds, and how the bacteria adapt to that pressure. We have recently demonstrated that aspects of Bburgdorferi meningeal infections can be modeled in laboratory mice, which opens up a lot of research avenues. In particular, we are interested in the behavioral changes that occur as a result of meningeal infection. For instance, anxiety and memory problems are often reported by Lyme patients, particularly in people with long-term disease or Post-Treatment Lyme Disease Syndrome, and we want to understand how the Lyme disease bacterium and the host immune system contribute to these devastating symptoms. Having a small animal model allows us to more easily test potential treatments and interventions in the lab, prior to testing in people.


CB: Absolutely. Lyme researchers, like Lyme patients, are tenacious and persistent. We won’t stop.


  • “Adverse outcomes in gestation as a consequence of immune responses to B.  burgdorferi infection during pregnancy” (2017-18)
  • “Control of Bb DNA expression” (2016-17)


  1. Divan, A., Casselli, T.,Narayanan, S.A., Mukherjee, S., Zawieja, D.C., Watt, J.A., Brissette, C.A., Newell-Rogers, M.K. (2018) Borrelia burgdorferi adhere to blood vessels in the dura mater and are associated with increased meningeal T cells during murine disseminated borreliosis. PLoS One 13(5):e0196893. doi: 10.1371/journal.pone.0196893. PMID: 29723263
  2. Greenmyer, J., Gaultney, R.A., Brissette,A., Watt, J.A. (2018) Primary human microglia are phagocytically active and respond to Borrelia burgdorferi with upregulation of chemokines and cytokines. Front Microbiol. 9:811. doi: 10.3389/fmicb.2018.00811. PMID: 29922241
  3. Casselli, T., Qureshi, H., Peterson, E., Perley, D., Blake, E., Jokinen, B., Abbas, A., Nechaev, S., Watt, J.A., Dhasarathy, A@., Brissette@, C.A. (2017) MicroRNA and mRNA transcriptome profiling in primary human astrocytes infected with Borrelia burgdorferi. PLoS One 12(1):e0170961. doi: 10.1371/journal.pone.0170961. PMID: 28135303 @Co-corresponding authors
  4.  Brissette,A., E.D. Kees, M. Burke, R.A. Gaultney, A.M. Floden, and J.A. Watt (2013) The multifaceted responses of primary human astrocytes and brain microvascular endothelial cells to the Lyme disease spirochete, Borrelia burgdorferi.ASN Neuro 5(3). doi:pii: e00119. PMID: 23883071 Paper highlighted with a podcast: http://www.asnneuro.org/an/005/3/default.htm
  5. Brissette, C.A., H.M. Houdek, A.M. Floden, and T.A. Rosenberger (2012) Acetate supplementation reduces microglia activation and brain interleukin-1beta levels in a rat model of Lyme neuroborreliosis. J Neuroinflammation 9:249. PMID: 23134838

Click here to see GLA’s Research Report, detailing GLA’s research accomplishments

scientific advisory board

GLA Counters IDSA’s Criticisms of Tick-Borne Disease Working Group Report

GLA’s Chief Scientific Officer Provides Evidence-based Rebuttal of IDSA Letter to Head of HHS and Tick-Borne Disease Working Group Report


by Timothy J. Sellati, Chief Scientific Officer, Global Lyme Alliance

Last month, the Tick-Borne Disease Working Group (TBDWG) published its first report to the U.S. Congress, outlining an integrated, multi-pronged approach to the growing public health challenges posed by tick-borne diseases in the U.S. In response shortly thereafter, the Infectious Diseases Society of America (IDSA) sent a letter to to the Secretary of the U.S. Department of Health and Human Services (HHS) stating that if some key recommendations of the TBDWG are implemented, it “would cause significant harm to patients and public health.”

Below is a rebuttal to IDSA’s unfounded criticisms of the TBDWG, which we find hyperbolic in light of the hundreds of man hours worked on the part of dozens of stakeholders dedicated to collecting, collating, and drafting a roadmap to advance the prevention, diagnosis, and treatment of patients suffering from Lyme and other tick-borne diseases.

IDSA’s letter suggests that there are “significant concerns with the working group’s lack of transparency and minimal opportunities for meaningful public input.”

  • The basis for this concern is unclear given that a substantial effort was made to be inclusive of professionals within the academic research community, physicians at renowned academic institutions and in private practice, as well as members of the general public in the form of patients suffering from Lyme and other tick-borne diseases and their advocates. Through contacts with their colleagues and fellow patients sitting on the TBDWG a free flow of ideas and opinions has passed between various stakeholders not part of the working group as well as those on it. The more likely concern of the IDSA is that it could not control the working group’s deliberations and final report through which it means to ensure consistency with the society’s long-held, and some would argue entrenched, ideas about tick-borne disease. Paramount is IDSA’s long-held view that Lyme disease is easy to diagnose, easy to treat, and only very rarely results in lasting consequences of infection. On the contrary, the overwhelming consensus among tick-borne disease researchers is that Post Treatment Lyme disease Syndrome occurs in 10 to 20% of those who received early treatment.


IDSA’s letter also suggests that if implemented, some recommendations of the TBDWG “would cause significant harm to patients and public health.”

  • Besides IDSA’s having only very limited support in the peer-reviewed scientific and medical literature regarding unsafe alternative treatment options, this hyperbole seems intended to spread fear, especially when one takes into consideration tick-borne disease researchers’ ever-evolving clinical understanding of Lyme disease, as opposed to the IDSA’s obsolete mantra that Lyme is easy to diagnose, easy to treat and only rarely results in lasting consequences of infection.


We urge you to ensure that the federal government response to tick-borne diseases is solidly rooted in the best available scientific evidence.”

  • Any claim that the TBDWG is not solidly rooted in the best available scientific evidence is unfounded. TheTBDWG report draws from the efforts of subject-matter experts from such diverse organizations as Johns Hopkins University School of Medicine; Office of the Secretary, U.S. Department of HHS;Stanford University Lyme Disease Working Group; Deputy Director, Division of Vector-Borne Diseases, Centers for Disease Control and Prevention (CDC); Chief, Bacteriology and Mycology Branch, National Institute of Allergy and Infectious Diseases (NIAID); Medicare Hospital Health and Safety Regulations, Centers for Medicare and Medicaid Services, U.S. Department of HHS; Population Health Sciences and Health Services Research Center of the Institutional Centers for Clinical and Translational Research, Boston Children’s Hospital; Vector-Borne Disease Laboratory; and Maine Medical Center Research Institute, just to name a few.


IDSA suggests that the makeup of the TBDWG is “skewed to individuals with perspectives that do not align with the overwhelming majority of scientific evidence regarding the diagnosis and treatment of Lyme disease.”

  • Evidently, one organization’s definition of “skewed” is another group’s diverse voices, opinions, and peer-reviewed evidence. Ultimately it does not benefit the scientific and medical research enterprise nor the Lyme and other tick-borne disease patient community to hew to the notion IDSA promulgates, which is that “Lyme disease is easy to diagnose, easy to treat, and only very rarely results in lasting consequences of infection”. Moreover, one could effectively argue that at least a subset of IDSA members hold perspectives about the persistence of Lyme borreliosis despite initial antibiotic treatment and see the desperate need for alternative treatment strategies that “do not align” with current scientific evidence.


While IDSA acknowledges that the CDC case definition for Lyme disease is intended for use as an epidemiological tool, they suggest “it is it is incorrect to promulgate the notion that the components of the surveillance definition should not be used for clinical diagnosis”.

  • However, it is important to note as the CDC itself mentions throughout its webpage that the case definition provided is for purposes of surveillance. Nowhere is it mentioned that the case definition criteria listed should be used for clinical diagnostic purposes alone. The CDC goes on to state that “Surveillance case definitions establish uniform criteria for disease reporting and should not be used as the sole criteria for establishing clinical diagnoses, determining the standard of care necessary for a particular patient, setting guidelines for quality assurance, or providing standards for reimbursement.” Finally, the spurious nature of IDSA’s suggestion that components of the surveillance definition could or should be used for clinical diagnosis is evident in the fact that CDC research has confirmed that annual clinical case numbers for Lyme disease are approximately 10-fold higher than the number reported by the CDC. This upward revision of annual Lyme disease cases suggests that considerably more early Lyme diagnoses are being missed than are the result of inaccurate, ultimately non-Lyme, diagnoses being made.


IDSA acknowledges that “some patients who are successfully treated for Lyme disease continue to suffer from persistent symptoms after treatment”.

  • This statement is illogical, however, because a patient who continues to suffer from symptoms caused by infection cannot or should not be classified as successfully treated.


IDSA states that “There is clear, widely accepted scientific evidence indicating that a 10-28-day course of antibiotics, depending on the stage of Lyme disease, will kill the Lyme disease bacterium in humans in all but the rarest of cases”.

  • Unfortunately, IDSA refuses to acknowledge that there also is clear, widely accepted and compelling scientific evidence indicating that 10 to 20% of patients receiving a 10-28-day course of antibiotics progress to Post-Treatment Lyme Disease Syndrome, which has a clear clinical definition, or the more broadly clinically-defined state of chronic Lyme disease. If one considers the number of CDC-reportable cases for 2016 of 364,290 (based on surveillance case reporting to CDC multiplied by a 10-fold factor to account for estimated underreporting) then 36,429 to 72,858 patients annually progressing to PTLDS/chronic Lyme disease cannot reasonably be considered a rarity.


IDSA supports more research to improve diagnostic tools for Lyme disease and they correctly state that it is essential that clinical education is rooted in the best currently available evidence.

  • Yet it is unclear that medical school educators are explaining to students that the best currently available evidence suggests that a large percentage of patients suffer persistent symptomatology as a result of misdiagnosis of early Lyme disease due to deficiencies in the current two-tier test. It is also unknown whether students are instructed in the atypical size, shape and coloration of the erythema migrans (EM) rash, rather than the classic “bull’s-eye” rash, that can be observed in some, but not all Lyme patients. In fact, despite IDSA’s claims, according to the CDC only 70 to 80% of patients with Lyme disease reported to its surveillance system the presence of an EM rash.


IDSA supports increased federal funding for responses to tick-borne diseases and correctly notes that higher level funding should not come at the expense of funding for other diseases, including HIV. The IDSA letter goes on to state that “Pitting one disease against another, as suggested in the draft report, is counterproductive and costly.”

  • While everyone can agree with the former statement, the latter is a mischaracterization of the content and intention of the TBDWG report. Suggesting that the level of funding for Lyme and other tick-borne diseases should be commensurate with the case incidence rates is not pitting one infectious disease against another; it is, rather, a fair-minded plea for equitable distribution of limited funds based on current public infection risk. Making comparisons between Lyme disease and HIV merely highlights the disproportionate distribution of funding if one looks solely at case incidence rates for the two diseases.


Please reach out to [email protected] with any questions.

Click here for a list of GLA’s published research findings.
Click here to read GLA’s comprehensive Research Report.

tick-borne disease research

Requests for Tick-borne Disease Research Reach an All-Time High

by Mayla Hsu, Ph.D., Director of Research & Science, GLA

It is no surprise that when funding for research lags, associated progress in science and medicine slows. Perhaps no area of health research illustrates this fact better than that focusing on Lyme disease. Despite infecting at least 329,000 people in the U.S. each year, according to the CDC, and being known by the medical community for over 40 years, Lyme disease is still responsible for vast numbers of disabled and chronically ill sufferers. Global Lyme Alliance (GLA) has made great strides to fill the dearth of knowledge by funding high-level science, awarded to academic scientists for each of the past 20 years.

The current crop of grant applications are especially exciting in terms of their scientific breadth and depth. We have received 31 proposals from the U.S. and abroad, with 18 of them from researchers in Lyme-endemic U.S. states. The total amount requested was a record, totaling over $8 million, attesting to the strong interest in Lyme disease research among investigators. Of all the applicants, 25 (81%) have not previously been funded by GLA, which speaks to our growing acceptance and reputation among top researchers.

The applications received span a broad spectrum of research interests in the tick-borne disease field. Among them were creative ideas to improve Lyme disease diagnostics with new technologies which would allow more rapid and highly sensitive detection of Borrelia together with co-infecting microbes. Some proposals sought to study patient populations to better identify individuals with tick-borne infections and their co-morbidities. Support of biobanks to collect patient samples, in association with careful clinical data, was also requested. Some applications propose to study tick biology and environmental influences, and tick-bacteria interactions, which may reveal improved disease exposure prevention strategies. There were also inspiring applications for discovering and developing new potential treatments, and clinical science proposals which sought to understand the mechanisms of inflammation and pathology in organs targeted by Borrelia burgdorferi.

GLA’s rigorous process for evaluating grant applications, unique among Lyme disease nonprofits, is closely modeled on the peer-review guidelines used by the National Institutes of Health. Sixteen Scientific Advisory Board (SAB) members, consisting of scientists in industry and academia —who are all noted experts in medical research, immunology, and microbiology— are assigned applications in their respective fields of expertise.

Each application is then reviewed according to strict criteria. This process is followed by a series of discussions to ensure that only the most promising applications, directed by the most qualified and creative scientists, are funded. Throughout the grant selection process, GLA seeks those applications with a high likelihood of leading to evidence-based, validated scientific advances as a means of ensuring maximum potential effectiveness. The 2018-2019 grants will be announced in January 2019.

View GLA’s Lyme Disease Research Report

essential oils_lyme disease research

GLA POV: Essential Oils as Treatment Against Lyme Disease

by Mayla Hsu, Ph.D., Director of Research and Science, GLA

Global Lyme Alliance’s Director of Research and Science offers perspective on newly published research on using essential oils to treat Lyme disease


Global Lyme Alliance (GLA)-funded investigator Ying Zhang, Ph.D. (Professor at Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health) details new findings on the effectiveness of certain essential oils to treat Lyme disease; “Identification of Essential Oils with Strong Activity against Stationary Phase Borrelia burgdorferi.”

Persister forms of B. burgdorferi, the bacterium that causes Lyme disease, are dormant or slow-growing, and tolerant of antibiotic treatment. It’s not clear yet whether persister bacteria, immune dysfunction, or some combination of the two is responsible for post-treatment Lyme disease syndrome (PTLDS), in which patients treated with antibiotics continue to suffer symptoms.

The search for novel compounds to kill persister bacteria has led to the discovery that essential oils (EOs), aromatic compounds produced by plants, may be promising. In an article published in Antibiotics, a peer-reviewed journal, scientists led by Dr. Ying Zhang identified 10 EOs that have strong activity against stationary phase B. burgdorferi at a low concentration of 0.1%. The study, underwritten by GLA, found that of the 10 EOs, those of garlic, allspice, and Palmarosa were active at even at 0.05% concentration. In addition, cinnamaldehyde, a major ingredient isolated from cinnamon bark, was active against both stationary phase bacteria as well as replicating B. burgdorferi at a 0.02% concentration.

A stringent test of antimicrobial activity against stationary phase bacteria is the capacity to block subcultured bacteria from growing. This means that after killing bacteria in culture with the inhibitor, a small amount of that culture is transferred to fresh growth media that lacks the inhibitor. Any regrowth indicates that the inhibitor did not completely kill all bacteria from the original culture. Under these conditions, only garlic and cinnamaldehyde were effective against the regrowth of B. burgdorferi spirochetes subcultured for 21 days.

These results indicate that certain EOs or their ingredients are potent in eliminating persister B. burgdorferi, and should be studied in greater depth to analyze their utility as potential treatments.

Calprotectin_research pov

GLA POV: Antimicrobial Action of Calprotectin That Does Not Involve Metal Withholding

by Timothy Sellati, Ph.D., Chief Scientific Officer, GLA



A Global Lyme Alliance (GLA)-funded investigator, Valeria Culotta, Ph.D. (Department of Biochemistry and Molecular Biology, Johns Hopkins Bloomberg School of Public Health), and her research group recently published an entirely unexpected finding regarding how our immune system protects us against invading pathogens. Transition metals such as manganese (Mn), zinc (Zn), copper (Cu), and iron (Fe) are essential micronutrients for virtually all living organisms. Yet these same metals are potentially toxic, and the host exploits this “double-edged sword” by either attacking pathogens with high/toxic levels of metals or by starving the invading microbe of metal micronutrients through a process called nutritional immunity.  Nutritional immunity is one of several defenses our body mounts against pathogens like Escherichia coli. A key protein involved in nutritional immunity is calprotectin, a potent antimicrobial that inhibits the growth of pathogens by tightly binding Mn and Zn thus preventing microbial growth.

Borrelia burgdorferi, the bacterial spirochete causative agent of Lyme disease, is rather unique in the bacterial world and with regard to metal biology in that it has no requirement for Cu or Fe. In contrast, B. burgdorferi does accumulate high levels of Mn through at least two uptake systems and Mn acquisition is essential for virulence, the bacterium’s ability to cause disease. The study by Angelique N. Besold and co-workers, published in the Royal Society of Chemistry journal Metallomics, shows that calprotectin is produced in the skin of Lyme disease patients by both keratinocytes of the epidermis and immune cells infiltrating the dermis, including macrophages. Thus, you might think spirochete growth would be inhibited through sequestration of Mn by calprotectin. On the contrary, what is remarkable and entirely unexpected is that, unlike with other bacteria such as E. coli, calprotectin does not inhibit growth of B. burgdorferi by restricting uptake of Mn or Zn. Instead, the mechanism of growth inhibition appears to require physical association of calprotectin with the bacteria. Though the exact mode of action needs to be determined, the importance of this finding derives from the fact that this novel means of blocking spirochete growth might aid in the identification of small molecule compounds that could mimic the effect of calprotectin, and thus have therapeutic benefit in the treatment of Lyme patients. An alternative to treatment with traditional antibiotics is desperately needed since as many as 20% of Lyme patients can develop Post-Treatment Lyme Disease Syndrome, of which antibiotic-resistant Lyme arthritis is one form.

Collectively, the results outlined in this new GLA-funded study provide evidence for the first time that calprotectin can inhibit bacterial growth without starving the microbe of essential metals. The capacity of calprotectin to act as an antimicrobial is indeed complex and, depending on the microbe and host niche, circumstances beyond nutritional immunity should be considered. Future studies will explore how this novel killing mechanism might be exploited for therapeutic benefit. Such efforts are consistent with GLA’s goal of expanding the repertoire of treatment options available to physicians treating an ever-expanding number of Lyme disease patients.

Besold AN, Culbertson EM, Nam L, Hobbs RP, Boyko A, Maxwell CN, Chazin WJ, Marques AR, Culotta VC. (2018) Antimicrobial action of calprotectin that does not involve metal withholding. Metallomics doi: 10.1039c8mt00133b

ying zhang

Meet the Researcher: Ying Zhang, M.D., Ph.D.


NAME: Ying Zhang, M.D., Ph.D.
TITLE: Professor at Department of Molecular Microbiology and Immunology
INSTITUTION: Johns Hopkins Bloomberg School of Public Health

Dr. Zhang’s research interests are focused on antibiotic resistance, bacterial persistence, and development of more effective treatments for a wide variety of persistent bacterial infections, including tuberculosis (TB). His group has identified persistence mechanisms in important bacterial pathogens including  M. tuberculosis, E. coli, S. aureus, and Borrelia. In addition, his group identified genes and pathways important for L-form bacteria formation. Recently he has been working on the challenging problem of persistent Lyme disease. Dr. Zhang’s group has identified a variety of FDA-approved drugs as well as some essential oils that are more effective in killing Borrelia burgdorferi persisters in vitro than the current Lyme antibiotics. Thanks in part to a GLA-funded grant, and in collaboration with colleagues, his group is evaluating promising drug candidates, including drug combinations and active essential oils in animal models for more effective treatment of Lyme disease and its co-infections.

Drs Janakiram Seshu_Ying Zhang_Research Symposium 2017
Drs Janakiram Seshu and Ying Zhang at GLA Lyme Disease Research Symposium 2017

GLA: What motivated you to focus on Lyme and tick-borne disease research?

YZ: In 2009, we published a paper on the molecular basis of E. coli L-forms (a type of persister bacteria), when I got a call from GLA’s Chairman Rob Kobre asking me for help with persistent Lyme disease. Rob asked me if I would be interested in studying Borrelia L-forms as persisters that may be related to persistent Lyme disease. I said yes, and the rest is history.

As I learned more about the great suffering caused by chronic Lyme disease, also known as Post-Treatment Lyme Disease Syndrome (PTLDS), that so far has no cure, I became more attracted to the mysterious features of the spirochete bacteria and its ability to cause persistent infections. It is an important aspect of the scientific challenge that has eluded us so far. Seeing so many people suffering from such a horrible disease has motivated me to find a more effective cure for chronic Lyme.

GLA: What discovery has been most gratifying?

ying zhang
GLA Board Member Norma Russo with Dr. Zhang at GLA Lyme Disease Research Symposium 2017

YZ: The most gratifying discovery is the identification of Borrelia persister drugs and mechanisms and the persister drug combination approach that more effectively eradicates Borrelia persisters in vitro. We are currently testing different drug combinations in vitro as well as in vivo in animal models. Moreover, we found some essential oils such as oregano, cinnamon bark, and clove bud, and garlic to be highly active against Borrelia persisters and especially against biofilm forms. The active essential oils are very interesting as they are natural products. However, in vivo testing including the dosing schedule, PK, and toxicity and efficacy in killing Borrelia in animal models will have to be done properly before subsequent human studies. I understand some patients are very sick and are desperate to try these on an anecdotal basis. Nevertheless, proper clinical trials will have to be conducted. In addition, we are working on a project that evaluates Borrelia persister antigens for improved diagnosis of Lyme disease, and preliminary results look encouraging.

GLA: Are you confident we’ll find a cure?   

YZ: First, “cure” is a relative term. Because of the heterogeneity and complexity of PTLDS, it is challenging to develop a regimen that will be effective for all such patients. However, based on encouraging in vitro data and the persister drug PZA principle as exemplified in TB treatment, more effective drug combinations for persistent Lyme disease will be developed. This means that at least some segments of persistent Lyme patients can be cured more consistently. However, funding for evaluating drug regimens and for new clinical trials is critically needed. In addition to persister drug regimens, host directed therapy (HDT) improving host immune function will also be important for a more effective cure. We are at a critical juncture and are encouraged by recent interest from the U.S. Department of Health and Human Services in Lyme disease. So I would say to chronic Lyme sufferers, do not give up! There is hope.

GLA-funded research grants with Dr. ZHANG include:

  • “High Activity of Selective Essential Oils Against Borrelia persisters” (2017-18)
  • “Persister Antibodies in PTLDS Patients?” (2016-17)
  • “Optimal Drug Combinations Targeting Bb Persisters for Improved Treatment of Lyme Disease” (2015-16)
  • “Targeting Dormant Bb Persisters for Improved Treatment of Chronic and Persistent Lyme” (2013-14)
  • “Identified Borrelia burgdorferi L-form specific Proteins (ie: Persisters) for Development of New Diagnostics, Vaccines and Also Drugs Targeting L-Form Borrelia” (2011-12)


  1. Identification of Novel Activity against Borrelia burgdorferi Persisters using an FDA Approved Drug Library. Emerging Microbes and Infections Jie Feng, Ting Wang, Wanliang Shi, Shuo Zhang, David Sullivan, Paul G. Auwaerter, Zhang Y (2014). Nature Publishing Group), July 2, 2014. 3, e49; doi:10.1038/emi.2014.53
  2. Drug Combinations against Borrelia burgdorferi Persisters In Vitro: Eradication Achieved by Using Daptomycin, Cefoperazone and Doxycycline Jie Feng, Paul G. Auwaerter, Zhang Y (2015). PLoS One, 2015 Mar 25;10(3):e0117207. doi: 10.1371/journal.pone.0117207
  3. Identification of Additional Anti-Persister Activity against Borrelia burgdorferi from an FDA Drug Library Jie Feng, Megan Weitner, Wanliang Shi, Shuo Zhang, David Sullivan, Zhang Y (2015). Antibiotics, 4(3), 397-410; doi:10.3390/antibiotics4030397
  4. Persister Mechanisms in Borrelia burgdorferi: Implications for Improved Intervention. Emerging Microbes & Infections Jie Feng, Wanliang Shi, Shuo Zhang, Zhang Y (2015)., 4, e51; doi:10.1038/emi.2015.51 https://www.nature.com/articles/emi201551
  5. Eradication of Biofilm-like Microcolony Structures of Borrelia burgdorferi by Daunomycin and Daptomycin but not Mitomycin C in Combination with Doxycycline and Cefuroxime Jie Feng, Megan Weitner, Wanliang Shi, Shuo Zhang, and Zhang Y (2016).. Frontiers in Microbiology, doi: 10.3389/fmicb.2016.00062. https://www.frontiersin.org/articles/10.3389/fmicb.2016.00062/full
  6. A drug combination screen with FDA-library drugs identifies agents active against amoxicillin-induced round bodies of Borrelia burgdorferi persisters Jie Feng, Wanliang Shi, Shuo Zhang, David Sullivan, Paul G. Auwaerter, Zhang Y (2016. Frontiers in Microbiology, 23 May 2016  http://dx.doi.org/10.3389/fmicb.2016.00743
  7. Ceftriaxone Pulse Dosing Fails to Eradicate Biofilm-like Microcolony B. burgdorferi Persisters Which Are Sterilized by Daptomycin/Doxycycline/Cefuroxime without Pulse Dosing Jie Feng, Shuo Zhang, Wanliang Shi, and Zhang Y (2016).. Frontiers in Microbiology, 04 November 2016  http://dx.doi.org/10.3389/fmicb.2016.01744
  8. Selective Essential Oils from Spice or Culinary Herbs Have High Activity against Stationary Phase and Biofilm Borrelia burgdorferi Jie Feng, Shuo Zhang, Wanliang Shi, Nevena Zubcevik, Judith Miklossy, and Ying Zhang (2017).. Front. Med., 11 October 2017 | https://doi.org/10.3389/fmed.2017.00169 

Click here to see GLA’s Research Report, detailing GLA’s research accomplishments


GLA POV: Identifying Vancomycin as an effective antibiotic for killing Borrelia burgdorferi

by Timothy Sellati, Ph.D., Chief Scientific Officer, GLA

Global Lyme Alliance’s Chief Scientific Officer offers perspective on newly published GLA-funded research out of Northeastern University


Although the underlying premise of a recent study by Wu et al. — “…that minimizing the time the pathogen interacts with the host will diminish the probability of developing PTLDS [Post-Treatment Lyme Disease Syndrome], irrespective of its nature.”[1] — is scientifically sound, the exact nature of PTLDS remains unknown.  PTLDS is characterized by persistent or recurrent symptoms of fatigue, musculoskeletal pain, and cognitive complaints leading to functional decline. It is recognized that currently approved antibiotics for treatment of Lyme disease fail to impact these symptoms after they develop. Thus, novel strategies that quickly and efficiently eradicate the pathogen during acute infection are needed to prevent patients from developing PTLDS in the first place.

Kim Lewis, Ph.D. (Department of Biology, Northeastern University), a Global Lyme Alliance (GLA)-funded investigator, set out in search of an antibiotic with superior capacity to kill Borrelia burgdorferi, the bacterial spirochete and causative agent of Lyme disease. Having examined approved antibiotics for their ability to kill B. burgdorferi, Lewis found Vancomycin to be more effective in killing B. burgdorferi in vitro (in a test tube culture) than Ceftriaxone, the current standard of care for disseminated Lyme disease. Vancomycin also was most effective in killing stationary-phase (i.e., non-replicating) bacteria. This is an extremely important, yet unexpected result given that inhibitors of cell wall biosynthesis (e.g., such as Vancomycin) are known to only kill growing bacteria. This seeming paradox was explained by finding that, unlike in other bacteria, peptidoglycan, a component of the cell wall, continues to be synthesized in stationary cells of B. burgdorferi.

The importance of this finding cannot be overstated. There is mounting evidence, now including non-human primate studies by GLA-funded investigator Monica E. Embers, Ph.D., of Tulane University to suggest that spirochetes may persist in mammalian hosts in a metabolically non-replicating state that make them resistant to treatment with Doxycycline, the primary antibiotic of choice for treatment of acute Lyme disease. Another intriguing observation is that although Doxycycline failed to clear B. burgdorferi in severe combined immune deficient (SCID) mice, Vancomycin was highly effective despite an impaired immune system. This is exciting insofar as many Lyme patients, with or without PTLDS, are often immune compromised due to tick-borne co-infections or other diseases that hobble their body’s ability to fight off the persisting spirochetes.

Collectively, the results outlined in this new GLA-funded study are cause for considerable encouragement and argue strongly for clinical trials to examine the impact and merits of earlier use of more potent antibiotics on development of PTLDS.

[1] Identifying vancomycin as an effective antibiotic for killing Borrelia burgdorferi.
Wu X, Sharma B, Niles S, O’Connor K, Schilling R, Matluck N, D’Onofrio A, Hu LT, Lewis K. Antimicrob Agents Chemother. 2018 Aug 20. pii: AAC.01201-18. doi: 10.1128/AAC.01201-18.

timothy sellati

Meet the Researcher: Timothy J. Sellati, Ph.D.

Meet the Researcher is a blog series to introduce GLA-funded Lyme disease researchers, and in this case, GLA’s Chief Scientific Officer.



NAME: Timothy J. Sellati, Ph.D.
TITLE: Chief Scientific Officer

Dr. Sellati has more than 20 years of Lyme and tick-borne disease research experience. He has published more than 40 peer-reviewed infectious disease papers, nearly 20 of which are focused on Lyme disease. As GLA’s Chief Scientific Officer, he leads GLA’s research initiatives to accelerate the development of more effective methods of diagnosis, the treatment of Lyme and other tick-borne diseases, and the search for a cure. But what makes him tick?

GLA CEO Scott Santarella, GLA grantee Dr. Nicole Baumgarth, GLA CSO Dr. Timothy Sellati
Dr. Sellati, far right, with GLA CEO Scott Santarella and GLA grantee Dr. Nicole Baumgarth at GLA’s Lyme Disease Research Symposium 2018


When I began pursuing my Ph.D. from the State University of New York at Stony Brook, I thought I would focus on cancer biology and tumor cell metastasis. Through serendipity I instead found myself training with Martha Furie, Ph.D., a renowned cell biologist, and Jorge Benach, Ph.D., who along with Willy Burgdorfer, Ph.D., discovered that the causative agent of Lyme disease Borrelia burgdorferi  is a bacterial spirochete transmitted by the bite of a black-legged (“deer”) tick.. Although the study of bacteria entering and then escaping from the bloodstream after a tick bite sounds worlds away from studying tumor cell metastasis, there really are some remarkable similarities.

Timothy Sellati
Dr. Sellati served as Distinguished Fellow and Chair of the Department of Infectious Diseases in the Drug Discovery Division at Southern Research Institute

For instance, small cell lung cancers spread via the bloodstream to the liver, lung, bones and brain, but not to other organs that also receive blood. In a similar fashion, B. burgdorferi spirochetes leave the site of inoculation and travel to the joints, heart, and brain, but not to other organs also receiving blood. I wanted to explore and understand why that was so and what controlled where the spirochetes (like cancer cells) could and could not go in the body. I also wanted to determine why certain immune cells responsible for killing and clearing B. burgdorferi instead invade the joint while a different type of immune cell invades the spirochete-infected heart.


Dr. Sellati with GLA grantee Dr. Lise Nigrovic at GLA’s Lyme Disease Research Symposium 2018

Joining GLA allows me to make a greater impact, beyond my own academic research program, in helping to solve the mystery of Lyme disease and better understand its impact on patients. I’m most excited about the opportunity to engage scientists and physicians willing to share and learn from one another, willing to approach their work in a cross-disciplinary, inter-departmental and cross-institutional manner and who are willing to alter their notion of “how the world works” when presented with experimental evidence that runs contrary to it. In essence, GLA enables me to serve as scientific ‘cupid,’ supporting young, mid-career, and senior research scientists and physicians who are inclined to “color outside the lines,” challenging conventional thinking and approaches and hopefully getting us to the finish line—preventing future cases of tick-borne illness and curing those individuals already infected.

What drew me to GLA was its reputation. Reviewing its roster of Scientific Advisory Board members, I saw many faces and names with whom I was familiar and had interacted with during my long research career. I was also excited to see the caliber of scientists and physicians whose research the organization had funded in the past or is currently funding.


GLA’s goal is to impact patients, and I believe the best way to do that is through research. My strategic vision for GLA is to identify and help direct funds to projects that will drive the development of more accurate and accessible diagnostic tests, treatments for chronic, or persistent, Lyme disease, and a cure. I believe these goals are realistically attainable.


(a small sample)

Induction of Interleukin 10 by Borrelia burgdorferi Is Regulated by the Action of CD14-Dependent p38 Mitogen-Activated Protein Kinase and cAMP-Mediated Chromatin Remodeling.

Sahay B, Bashant K, Nelson NLJ, Patsey RL, Gadila SK, Boohaker R, Verma A, Strle K, Sellati TJ.  Infect Immun. 2018 Mar 22;86(4). pii: e00781-17. doi: 10.1128/IAI.00781-17. Print 2018 Apr. 

CD14 signaling restrains chronic inflammation through induction of p38-MAPK/SOCS-dependent tolerance.

Sahay B, Patsey RL, Eggers CH, Salazar JC, Radolf JD, Sellati TJ.  PLoS Pathog. 2009 Dec;5(12):e1000687. doi: 10.1371/journal.ppat.1000687. Epub 2009 Dec 11.

NKT cells prevent chronic joint inflammation after infection with Borrelia burgdorferi.

Tupin E, Benhnia MR, Kinjo Y, Patsey R, Lena CJ, Haller MC, Caimano MJ, Imamura M, Wong CH, Crotty S, Radolf JD, Sellati TJ, Kronenberg M. Proc Natl Acad Sci U S A. 2008 Dec 16;105(50):19863-8. doi: 10.1073/pnas.0810519105. Epub 2008 Dec 5.

Natural killer T cells recognize diacylglycerol antigens from pathogenic bacteria.

Kinjo Y, Tupin E, Wu D, Fujio M, Garcia-Navarro R, Benhnia MR, Zajonc DM, Ben-Menachem G, Ainge GD, Painter GF, Khurana A, Hoebe K, Behar SM, Beutler B, Wilson IA, Tsuji M, Sellati TJ, Wong CH, Kronenberg M. Nat Immunol. 2006 Sep;7(9):978-86. Epub 2006 Aug 20.

Toll-like receptor 2 functions as a pattern recognition receptor for diverse bacterial products.

Lien E, Sellati TJ, Yoshimura A, Flo TH, Rawadi G, Finberg RW, Carroll JD, Espevik T, Ingalls RR, Radolf JD, Golenbock DT. J Biol Chem. 1999 Nov 19;274(47):33419-25.


lyme disease research

GLA: Lyme Disease Research Symposium 2018

Highlights from GLA’s 8th Annual Research Symposium with top Lyme Disease Researchers


by Timothy J. Sellati, Ph.D., Chief Scientific Officer, GLA
(pictured: GLA’s Scott Santarella and Dr. Timothy Sellati with GLA grantee Dr. Nicole Baumgarth)

The incidence of tick-borne diseases has reached epidemic proportions in the United States with more and more people seeking medical care for Lyme disease and its co-infections. As Lyme spreads across the country, scientists continue to grapple with a variety of pressing questions. How can we better diagnose and treat Lyme? Are there direct diagnostic strategies that can avoid the complications associated with indirect antibody-based detection methods? What new non-traditional treatment options are available to patients suffering from persistent symptoms despite prior treatment with conventional antibiotic regimens and what role does our gut microflora play in the clinical course of Lyme disease? Provocative questions such as these and many others were discussed at the 2018 Global Lyme Alliance Research Symposium, which was held May 10-12 in Greenwich, Connecticut.

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GLA research grantees: Drs. Ying Zhang, Klemen Strle, Nicole Baumgarth, Brian Fallon and Kim Lewis

Some 40 scientists from across the nation met to share their most up-to-date research findings about Lyme disease. They included researchers who had received GLA grants in 2017 as well as Scientific Advisory Board members who provide strategic guidance and direction for GLA’s research and scientific programs.

One important area of discussion during the two-day symposium was the targeting of persister forms of Borrelia burgdorferi, the causative agent of Lyme disease, with novel essential oil treatments shown to be effective in killing spirochetes in bacterial culture. Now these studies are being extended to test the ability of essential oils to treat mice, non-human primates, and eventually humans. Another research group described heritable drug tolerance in B. burgdorferi and has explored use of novel antibiotics derived from soil bacteria to kill persister B. burgdorferi. This same group, as well as other researchers in attendance, are investigating how disturbance of the microbiome, the “ecological community of commensal, symbiotic and pathogenic microorganisms” found in our bodies, might worsen and prolong the symptoms experienced by Lyme disease patients.

Also discussed was the 10-20% of Lyme disease patients who despite antibiotic therapy are not cured. Unfortunately, these patients often suffer debilitating joint and muscle pain, fatigue, and neurocognitive difficulties, which are termed post-treatment Lyme disease syndrome (PTLDS). The mystery of why people fail therapy is the subject of GLA-funded work, both in the mouse and non-human primate model of Lyme disease. Efforts to understand the immune response underlying PTLDS and what perpetuates a chronic inflammatory state are being spearheaded by the next generation of young Lyme disease research scientists, recent recipients of the “Deborah and Mark Blackman-GLA Postdoctoral Fellowships.” Their latest discoveries were presented in the form of scientific posters and these young postdoctoral fellows appreciated the opportunity to discuss their work with some of the leading senior research scientists in the field.

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Deborah Blackman with the “Deborah and Mark Blackman-GLA Postdoctoral Fellowship” recipients, Drs. George Aranjuez, Ashley Groshong, Bijaya Sharma, Chrysoula Kitsou, and Matthew Muramatsu

Another fascinating area of discussion centered on harnessing the power of metagenomics, proteomics, and metabolomics along with “big data” analysis to achieve precision diagnosis through identification of Lyme disease-specific biomarkers was another area of discussion. Measuring biomarkers of a person’s immune response to infection with B. burgdorferi coupled with novel methods to directly detect the presence of spirochetes in patient samples promises to replace the current gold-standard two-tier testing method, whose luster is tarnished by insufficient sensitivity and specificity, especially during acute or long-term chronic infection.

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GLA’s Dr. Mayla Hsu with Drs. Omar Green and Joel Tabb of Ionica Sciences

Finally, using a rat model of Lyme neuroborreliosis stunning fluorescent images were presented of B. burgdorferi invading what were thought to be sacrosanct regions of the brain. This work meshed seamlessly with a talk on the relationship between Lyme disease and the development of psychiatric disorders, and what changes in biomarker levels might be indicative of psychosis.

This year’s symposium concluded with a stimulating group conversation about the need for evidence of the persistence of B. burgdorferi after antibiotic treatment as well as the existence of biofilms in patients, and the coordination and sharing of “big data” results across research groups.

Once again, GLA was proud to host this gathering of leading scientists. The latest research findings will eventually be published in peer-reviewed scientific journals. Not only are we eager to see the final results, but will continue to support ongoing studies.

timothy sellatiTimothy J. Sellati, Ph.D., is Chief Scientific Officer at Global Lyme Alliance

As GLA’s Chief Scientific Officer, Dr. Sellati leads GLA’s research initiatives to accelerate the development of more effective methods of diagnosis and treatment of Lyme and other tick-borne diseases.

pre-exposure prophylaxis, borrelia burgdorferi

Promising New Research: PrEPping for Ticks

by Mayla Hsu, Ph.D.
Director, Research and Science
Global Lyme Alliance

Stopping Lyme disease before it starts. Promising new research based on pre-exposure prophylaxis, or PrEP.


It’s frustrating that there are so few ways to protect ourselves from Lyme disease. We use tick repellents, rodent and deer control, and search for ticks on our bodies. But none of these are completely foolproof. What we need is creative approaches that go beyond fundamental tick-bite prevention. Now, there is intriguing news of a potentially novel method of pre-treating humans with a protective antibody. If the approach is eventually successful, it may become possible to prevent infection even after being bitten.

Promising new research published recently in the Journal of Infectious Disease, although still very preliminary, paves the way for new ways to protect ourselves from Lyme disease. This study used a technique called pre-exposure prophylaxis, or PrEP.

The studies were led by Dr. Mark Klempner at Mass Biologics and the University of Massachusetts Medical School. Lyme disease results when people are bitten by ticks infected with the bacterium called Borrelia burgdorferi. This research team found that pre-treating mice with antibodies that bind to Borrelia burgdorferi protected the mice from becoming infected after being bitten by infected ticks.

Two of the antibodies had dose-dependent effect, which means that when less antibody was pre-treated, fewer mice were protected. When more antibody was pre-treated, more mice were protected. This is strongly suggestive that the protective effect was due to the presence of the antibody. In contrast, a control antibody that does not recognize Borrelia failed to protect mice, who became infected.

Antibodies are proteins made by our immune systems to stave off infections. Some antibodies stick to bacteria and prompt immune cells to find and digest them. Other antibodies, once bound to bacteria, recruit defense proteins called complement proteins, which poke holes in microbes and kill them. Like a lock and key, antibodies recognize specific bacterial shapes, sticking only to precise locations on them. In other words, they direct immune defenses to highly specific places, leaving healthy bystander cells safely alone.

But not all antibodies work well. Initially, the research group immunized mice with OspA protein, which is on the outer surface of Borrelia burgdorferi. In response, hundreds of antibodies recognizing OspA were produced by the mice. But only four were able to promote the killing of Borrelia. In addition, these four antibodies targeted not only Borrelia burgdorferi, but also Borrelia garinii and Borrelia afzelii, two species of Borrelia bacteria that cause Lyme disease in Europe and Asia.

When the four antibodies were analyzed in depth, the team found that they all bound the purified OspA protein and recognized defined domains, or portions of OspA. Identifying these particular parts of OspA that are bound by the effective antibodies showed important potential targets for design of future vaccines or new Borrelia-targeted drugs. It was these four that were tested, and found effective at protecting mice from infection by Borrelia-harboring ticks.

The research results also suggest that certain parts of the OspA protein are common to all three species of Borrelia, even though there are other genetic differences between them. It shows that there might be a way to potentially block all three from infecting people. Naturally, this which would be enormously useful for people at risk for Lyme disease in other parts of the world as well as in the U.S.

Although a limited number of mice were studied, this data shows what is called  “proof-of-concept” that an antibody pre-treatment strategy might work to prevent infection by Lyme bacteria. The authors were careful to interpret their results cautiously, noting that we do not yet know whether the protection might last the duration of tick season, or even whether protection against all strains of Borrelia burgdorferi is possible.

These findings are only the beginning of a process for developing new preventive medicine and vaccines. Nonetheless, they are encouraging. They provide a rationale for continuing to develop this strategy, and raise the hope that another protective tool might eventually be available in our defense against Lyme disease.

Mayla Hsu, Ph.D.
Director, Research and Science
Global Lyme Alliance

Mayla manages GLA’s research grant program, working with the Scientific Advisory Board and creating viable partnerships to help advance the development of a reliable diagnostic test, effective treatments and ultimately a cure for Lyme.

Borrelia bacteria in the blood

GLA: Lyme Disease Research Symposium Highlights

by Mayla Hsu, Ph.D
Director of Research and Science, GLA

GLA hosts top researchers to discuss Lyme disease research.


How can we understand Lyme disease better? Are there drugs that can kill persistent bacteria? Why do some Lyme patients get well, while others remain sick? Questions like these were discussed at the 2017 Global Lyme Alliance Research Symposium, which was held March 31-April 1 in Greenwich, CT.

About 30 scientists from all over the United States met to share the latest data about Lyme disease. These were researchers who have received GLA grants, as well as Scientific Advisory Board members whose expertise spans both the clinical and basic sciences.

Norma Russo, board member, GLA; Dr. Ying Zhang, Johns Hopkins University
Norma Russo, board member, GLA; Dr. Ying Zhang, Johns Hopkins University

One highlight was the discussion of a new way of using the mouse model of Lyme disease, in which evidence of brain penetration by spirochetes has been found. In the past, this has not always been easy to demonstrate, and the new data will fuel further discovery of its direct effect on neurological infection and brain function.

Another area of discussion was focused on the 10-20% of Lyme disease patients who despite antibiotic therapy are not cured. Such patients often suffer debilitating pain, fatigue, and neurocognitive difficulties, which are termed post-treatment Lyme disease syndrome (PTLDS). Understanding the immune response in PTLDS patients and what causes a chronic inflammatory state is the subject of GLA-funded work, both in the mouse model as well as in the study of human subjects.

The search for more effective treatments for Lyme disease patients was also presented in talks and posters. The bacterium that causes Lyme disease is called Borrelia burgdorferi. When grown in the test tube and treated with antibiotics, some bacteria survive as persisters, which are very slow-growing bacteria. In patients, persisters may be the cause of long-lasting symptoms. Therefore, new drugs and drug combinations that directly target persister bacteria are a focus of research interest.

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Lew Leone, board member, GLA: Dr. Armin Alaedini, Columbia University

The symposium wrapped up with a lively group conversation about the diagnostic blood test for Lyme disease, with widespread agreement that the existing two-tiered test recommended by the Centers for Disease Control is unacceptably insensitive. What it should be replaced with, however, is still being debated.

Overall, GLA was pleased to host this gathering of premier-level scientists. The newer research underway will in due course be published in high-quality, peer-reviewed scientific journals consulted by authorities in the tick-borne research field. We look forward to seeing the final results and to supporting ongoing studies.

The Mighty White-Footed Mouse

by Mayla Hsu, Ph.D., GLA Director of Research and Science

What makes the white-footed mouse more mighty than a lab mouse when it comes to tolerating Borrelia burgdorferi, the bacterium that causes Lyme disease?


When we think of mice, we envision cute furry rodents with big eyes and little feet, and we don’t usually associate them with disease. But when we discuss Lyme disease, we need to consider the wild, white-footed mouse because it is one of the most important reasons for the spread and continued existence of this illness.

Dr. Alan Barbour at the University of California at Irvine is a pioneer in tick-borne disease research and a Global Lyme Alliance grantee. He published a recent article that explained why it is important that we study Lyme disease in wild mice and not only in lab mice.

Peromyscus leucopus—the scientific name of the white-footed wild mouse—is abundant in North America, along with its close relative, Peromyscus maniculatus. Together, they act as natural hosts, or reservoirs, for numerous disease-causing microbes. This means that they provide a long-term home for pathogens to survive in nature. They are also blood meal sources for vectors, like ticks, which transmit the pathogens from one animal to another.

One reason why we should study Lyme disease in wild mice, Dr. Barbour writes, is because they are genetically quite distant from lab mice. Peromyscus mice are actually more closely related to hamsters and voles than to lab mice, which are genetically grouped with the black rat. The genetic distance between the species might explain why there are important differences in how wild mice and lab mice respond to pathogens like Borrelia burgdorferi, the bacterium that causes Lyme disease.

Capture of wild field mice indicates that compared to other small mammals, they are more heavily burdened by ticks. Although there is variation between different studies, up to 100% of these ticks have been found infected with B. burgdorferi. Dr. Barbour summarized studies showing that in the northeast and north-central United States, P. leucopus mice typically get infected during the spring and summer months. As part of their immune response, they produce antibodies in their blood that recognize OspC, a protein on the outside of the bacteria. This also occurs in lab mice and in humans infected with Lyme disease, suggesting that this part of the immune response is common to all three.

blog_mayla_white footed mouse_quoteBut what’s different about wild Peromyscus mice is that they exhibit no obvious pathology. In multiple studies, even though the bacteria could be recovered from the urinary bladder, kidney, heart, spleen, ears, tails and joints, there was no evident organ damage. There was no variation in the types of immune cells found in infected animals as compared to uninfected animals. Infected animals did not appear to differ in their body weight from uninfected ones, suggesting that there was no obvious impact on overall health. And the amount of time that Borrelia-infected P. leucopus mice spent running on their exercise wheels did not differ from the uninfected mice.

In contrast, lab mice, when challenged by Borrelia burgdorferi infection, typically develop arthritis, carditis, and joint inflammation. Studying infection in these animals is useful to understand how the bacteria cause disease and the dysfunction of the immune response, but that only tells part of the story.

It’s not well-understood why Peromyscus mice don’t get sick from Lyme bacteria, but we do have some clues. It has been speculated that B. burgdorferi infections have occurred for hundreds of years in North America. With time, it is likely that the host-pathogen relationship evolved into a balance allowing both of them to survive. While in the mouse, the pathogen has to reproduce to sufficient levels so that it can enter ticks and be transmitted from one animal to another.  But the pathogen can’t kill its host, or weaken it so that it can’t efficiently reproduce. The mouse host must live long enough to have progeny, in order to produce a new generation of hosts in which the pathogen can be maintained.

Somehow, Peromyscus mice are able to tolerate Borrelia infection without any obvious illness. If we study these animals, especially by comparing the immune response in both uninfected and infected mice, we may be able to learn much that might explain how Peromyscus mice avoid the damage caused by B. burgdorferi infection.

What the proposed NIH budget cuts mean for Lyme disease research

GLA CEO Scott Santarella shares his view on what the proposed NIH budget cuts could mean for Lyme and tick-borne disease research.


by Scott Santarella, CEO, Global Lyme Alliance

As we learned last week, the Trump administration’s projected fiscal 2018 budget constitutes a radical reallocation of federal spending. The $5.8 billion in proposed cuts to the National Institutes of Health (NIH) budget would alone effectively defund thousands of biomedical research programs—in order to fund more military spending.

While this budget will be debated for some time to come, we are convinced that the proposed cuts would represent a grievous setback for Lyme and tick-borne disease research. The view that the security and prosperity of our country must come at the expense of medical research is simply incorrect. Research is an economic driver.

Government funding for Lyme and tick-borne disease research is already minimal, with only 17% of applications addressing Lyme approved by NIH every year. Yet the loss of even that small increment of funding would represent an unprecedented abandonment of those individuals suffering from this terrible disease.

Global Lyme Alliance is a dynamic and rapidly growing organization whose contributions to improved diagnostics and treatment modalities have been crucial. Still, it would take us years to supplant the lost NIH investment in Lyme and tick-borne disease research. The Lyme community cannot afford to face a gap of years in which research progress is static.

Lyme and tick-borne disease patients already face the great injustice of still having no definitive diagnostic test and only limited treatment options. Left untreated, or inadequately treated, Lyme’s victims suffer devastating health outcomes. To further compound that injustice by thwarting research progress is unconscionable. With 329,000 people in the U.S. diagnosed with Lyme disease annually, this is the wrong time for surrender.

Global Lyme Alliance will continue to do what it has always done to maximize its fundraising operations. But make no mistake, the loss of NIH research dollars would be deleterious beyond our imagining. We hope you will make your voice heard and send a clear message to your Congressional representatives to ensure federal funding levels for Lyme and tick-borne research remain strong.

Scott Santarella

Letter from CEO on Lyme Disease Research Initiatives

Global Lyme Alliance CEO Scott Santarella highlights key research initiatives in the 2015-2016 grants cycle.


Thanks to the generosity of our donors, Global Lyme Alliance has had an exceptionally productive year. We have awarded over $1 million in new research grants during the 2015-2016 grants cycle. This constitutes nine new studies, an all-time institutional high, by exceptional researchers at leading U.S. universities.

With 329,000 new cases of Lyme each year, and very limited federal funding, privately-funded research like GLA’s is more critical than ever. Without question, the quality of our Lyme research is second to none. GLA’s outstanding grantees are conducting exciting research in diagnostics, disease processes and potential treatments. In fact, our grantees are the paradigm busters who are closely followed by the rest of the Lyme community. Current grantees are:

  • Armin Alaedini, Ph.D., Columbia University, is identifying how antibodies change with disease progression in Lyme patients;
  • Nicole Baumgarth, DVM, Ph.D., UC-Davis, is analyzing how the immune system responds to Lyme bacteria;
  • Chris Janson, M.D., UI-Chicago, is focused on the neurological effects of Lyme;
  • Alla Landa, Ph.D., Columbia University, is studying chronic pain in post-treatment Lyme syndrome patients;
  • Kim Lewis, Ph.D., Northeastern University, has tested pulse-dosing antibiotics to more effectively treat Lyme patients;
  • Benjamin Luft, M.D., SUNY-Stony Brook, is developing new diagnostic tests;
  • Karen Newell-Rogers, Ph.D., Texas A&M University, is studying neurological Lyme disease in mice;
  • Eva Sapi, Ph.D., University of New Haven, continues her work studying biofilms;
  • Ying Zhang, M.D., Ph.D., Johns Hopkins University Bloomberg School of Public Health, is evaluating possible drug combinations for Lyme treatments.

Meanwhile, four distinguished new members have joined our Scientific Advisory Board. They are Catherine Brissette, Ph.D., University of North Dakota; Richard Goldstein, DVM, Chief Medical Officer, Animal-Medical Center; Andreas Kogelnik, M.D., Ph.D., director of the Open Medicine Institute, and Neil Spector, M.D., Duke University.

Our spectacular momentum comes down to a single, irreducible phenomenon: our donors. I hope you will join us at our 2nd annual “Uniting for a Lyme-Free World” Gala on Thursday, October 13, 2016, at Cipriani 42nd Street in New York City. As GLA’s new CEO, I look forward to meeting you at what promises to be a very special event.

Scott Santarella