New Study Reveals Potential Treatment for Neurologic Lyme Disease

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 New Study Reveals Potential Treatment for Neurologic Lyme Disease

Blocking certain fibroblast growth factor receptors is shown to be effective in reducing inflammation and cell death caused by neurologic Lyme infection in laboratory studies

PORTOLA VALLEY, Calif. April 18, 2024—Bay Area Lyme Foundation, a leading sponsor of Lyme disease research in the US, recently announced the publication of a laboratory study showing that fibroblast growth factor receptor (FGFR) inhibitors may be appropriate as an anti-inflammatory supplementary treatment for neurologic Lyme disease, for which there are no universally effective treatments. Published in the peer-reviewed journal Frontiers in Immunology, this study shows FGFRs are activated in response to both live and non-viable Lyme bacteria in preclinical brain tissue models. Further, inhibition of FGFR1, FGFR2, and FGFR3 may help mitigate the neuroinflammatory and neuropathogenic effects of infection by the bacteria that causes Lyme disease, Borrelia burgdorferi.  

“Our research shows a potential connection between neurological Lyme disease and several other neurological conditions, and this common pathway may explain why Lyme can be confused with many other conditions. Increasing our knowledge of FGFRs and their effect on the brain will help us understand the common mechanisms that may underlie Lyme disease and other neurological diseases,” said Geetha Parthasarathy, PhD, assistant professor at Tulane National Primate Research Center, Tulane School of Medicine, and a Bay Area Lyme Foundation 2019 Emerging Leader Award winner. “This data shows that FGFRs can be novel targets of anti-inflammatory therapeutics in Lyme patients with persistent neuroinflammation.”

“Our findings from this and our previous studies also offer important insight that may help to explain why some patients still experience chronic neurological symptoms even after a short course of antibiotics,” added Dr. Parthasarathy.

Her previous studies have shown that Borrelial remnants can be neuropathogenic in nervous tissues. In this study, Dr. Parthasarathy and her team demonstrated that FGFR receptors 1, 2, and 3 are activated in response to both live and non-viable B. burgdorferi when added to ex vivo nervous tissues and that these receptors are proinflammatory; this inflammation can lead to apoptosis, or cell death. As FGFRs are also implicated in other neurological conditions, activation of such pathways in the nervous system by Borrelial remnants can likely contribute to these neurological conditions even after the removal of live infection.

“Lyme neuroborreliosis, or neurologic Lyme, causes the most disabling symptoms in Lyme disease, yet there has been relatively little study of the disease mechanisms caused by the infection. There has long been a question about whether the persistent neurological symptoms of Lyme disease are caused by live bacteria or bacterial remnants. This study not only answers this question by demonstrating that both live and non-viable bacteria may cause these symptoms, but also suggests that inhibition of certain FGFRs may offer a path to effective treatments,” said Wendy Adams, research grant director, Bay Area Lyme Foundation. “We desperately need treatment options for the brain fog, sleep disturbance, neuropsychiatric disorders, and memory and functional deficits that can disable people with advanced stages of Lyme,” added Adams.

In this study, two research compounds, an FGFR1 inhibitor, and an FGFR1-3 inhibitor, were effective in downregulating inflammation in response to live Lyme bacterium in the frontal cortex of the brain and the dorsal root ganglion. The FGFR1 inhibitor was efficacious in downregulating the inflammatory response in both the frontal cortex and dorsal root ganglion in response to non-viable Borrelia bacterial remnants, but the FGFR1-3 inhibitor was less so. 

FGFRs also play a role in many developmental and metabolic disorders and cancer. While there are currently FDA-approved FGFR inhibitors for cancer, those drugs would most likely not be suitable for use in Lyme disease patients because of their toxicity profile. However, based on further findings in the study, the researchers believe that two biologics (such as monoclonal antibodies) may be needed to effectively curb persistent neuroinflammation and pathology in the central nervous system and peripheral nervous system of neurologic Lyme patients. 

Funding for this study was provided by the Bay Area Lyme Foundation, with support from Project Lyme and TNPRC base grant P51 OD011104.

About Lyme disease
The most common vector-borne infectious disease in the US, Lyme disease is a potentially disabling infection caused by bacteria transmitted through the bite of an infected tick to people and pets, and may also be passed from a pregnant mother to her unborn baby. If caught early, most cases of Lyme disease can be effectively treated, but it is commonly misdiagnosed due to a lack of awareness and inaccurate diagnostic tests. There are approximately 500,000 new cases of Lyme disease each year, according to statistics released in 2018 by the CDC. As a result of the difficulty in diagnosing and treating Lyme disease, up to two million Americans may be suffering from the impact of its debilitating long-term symptoms and complications, according to Bay Area Lyme Foundation estimates. 

About Bay Area Lyme Foundation
Bay Area Lyme Foundation, a national organization committed to making Lyme disease easy to diagnose and simple to cure, is the leading public not-for-profit sponsor of innovative Lyme disease research in the US. A 501c3 organization based in Silicon Valley, Bay Area Lyme Foundation collaborates with world-class scientists and institutions to accelerate medical breakthroughs for Lyme disease. It is also dedicated to providing reliable, fact-based information so that prevention and the importance of early treatment are common knowledge. A pivotal donation from The LaureL STEM FUND covers overhead costs and allows for 100% of all donor contributions to the Bay Area Lyme Foundation to go directly to research and prevention programs. For more information about Lyme disease or to get involved, visit www.bayarealyme.org or call us at 650-530-2439.

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