New Study Reveals Potential Treatment for Neurological Lyme Disease
April 18 2024 - 11:00AM
Bay Area Lyme Foundation, a leading sponsor of Lyme disease
research in the US, recently announced publication of a laboratory
study showing that fibroblast growth factor receptor (FGFR)
inhibitors may be appropriate as anti-inflammatory supplementary
treatment for neurological 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 removal of live infection.
“Lyme neuroborreliosis, or neurological 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, and 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 neurological Lyme patients.
Funding for this study was provided by the Bay Area Lyme
Foundation, 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 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.
Media contact: Tara DiMilia Phone:
908-369-7168 Tara.DiMilia@tmstrat.com