FGFR Inhibitors and lyme inflammation - mechanisms of old standby treatments and possibly new treatments for lyme

A 2024 study out of Tulane University elucidated a mechanism in which lyme and post lyme / long lyme patients can experience chronic neuroinflammatory symptoms. . The research focuses on fibroblast growth factor receptors (FGFRs), a family of proteins involved in various cellular processes. Dysregulation of FGFRs is implicated in a variety of diseases, and now this study suggests that Lyme disease may be among them.

The Tulane study specifically investigated the role of FGFRs in the neuroinflammation associated with Lyme disease, particularly in patients who experience lingering neurological symptoms even after antibiotic treatment. These symptoms, which can include brain fog, fatigue, and nerve pain, can be debilitating and significantly impact a patient's quality of life.

The persistent activation of FGFRs might contribute to this ongoing neuroinflammation. The researchers infected human brain and nerve tissue samples with Borrelia burgdorferi, the bacteria that causes Lyme disease. They then treated these infected samples with various FGFR inhibitors, including some already approved for cancer treatment.

The results were encouraging. FGFR inhibition significantly reduced several markers of neuroinflammation, including the production of pro-inflammatory cytokines and the activation of microglia (the brain's immune cells). Importantly, the FGFR inhibitors also reduced neuronal cell death caused by the Lyme bacteria.

This research suggests that targeting FGFR signaling pathways could be a potential therapeutic strategy for symptoms that persist after lyme disease, offering a new avenue for treating the persistent neurological symptoms that many patients experience. It would suggest a repurposing of drugs normally used in cancer.

These drugs can have significant risk and side effects, but there are likely many botanical and natural compounds that have similar effects. There may be other medications that have similar effects as well which may have a different safety and side effect profile that may be more favorable.

Although research specifically on natural FGFR inhibition is limited, several natural compounds show promise due to their observed effects on related pathways and general anti-inflammatory properties. These have not been as rigorously studied for FGFR inhibition as pharmaceutical drugs, but have 1) data on other anti-inflammatory effects as well and 2) are widely used by myself in treating chronic neuroinflammatory symptoms.

Some natural compounds with potential FGFR inhibition activity which I commonly use include:

• Curcumin (Turmeric): Curcumin has pleiotropic effects, including anti-inflammatory and anti-cancer properties. While direct FGFR inhibition isn't fully established, it influences related signaling pathways and may indirectly affect FGFR activity.
• Resveratrol (one of the compounds in Japanese Knotweed): Resveratrol has shown promise in preclinical studies for various conditions. Some evidence suggests it may interfere with FGFR signaling, though more research is needed to confirm direct inhibition. It is one of the main compounds in the herb Japanese knotweed, which is commonly used as an herbal option to treat lyme infection.
• EGCG (Green Tea): Epigallocatechin gallate, a major polyphenol in green tea, has demonstrated anti-cancer properties and influences various cellular processes. While not a direct FGFR inhibitor, its effects on related pathways could have an indirect impact.
• Quercetin: This flavonoid is known for its antioxidant and anti-inflammatory properties. Some studies suggest it may affect tyrosine kinase activity, potentially including FGFRs.
• Genistein (from Soybeans): A soy isoflavone, genistein has been studied for its potential anti-cancer effects. It may influence various signaling pathways, and some preliminary evidence suggests it could interact with and lower FGFRs

It's important to remember that the Tulane study is a significant step, but it is still preclinical research. Clinical trials are needed to determine if FGFR inhibitors are safe and effective for treating PTLDS in humans. However, this research provides hope for Lyme patients who have long suffered from persistent neurological symptoms. It also opens up exciting possibilities for exploring the potential of other natural compounds and medications to support this anti-inflammatory approach.