What if some of the neurological symptoms that persist after Lyme disease are being driven not only by living bacteria—but by the inflammatory aftermath they leave behind?

Researchers at Tulane University are investigating exactly that possibility.

In a 2024 study published in Frontiers in Immunology, researchers at the Tulane National Primate Research Center found that blocking a family of cellular receptors known as fibroblast growth factor receptors, or FGFRs, substantially reduced inflammation and cell death in nervous-system tissue exposed to Borrelia burgdorferi, the bacterium that causes Lyme disease. (Frontiers)

Perhaps even more interestingly, the effect was observed when tissues were exposed not only to live bacteria, but also to non-viable fragments of the organism.

That raises an important possibility for understanding post-treatment Lyme disease:

The bacterium may not always have to be alive to continue provoking biological effects.

The study does not establish a treatment for patients. It was an ex vivo experiment using rhesus macaque nervous-system tissue—not a human clinical trial.

But it provides a potentially important clue about why neurological inflammation might continue after Lyme disease and identifies a biological pathway researchers could potentially target therapeutically.

The Problem of Persistent Symptoms After Lyme Disease

Most patients treated for Lyme disease improve with antibiotics.

But some continue to experience symptoms after treatment, including:

• fatigue
• cognitive difficulties
• memory problems
• neuropathic symptoms
• joint or muscle pain
• sleep disturbances
• neurological complaints

This constellation is frequently referred to in research as post-treatment Lyme disease syndrome, or PTLDS.

The Tulane researchers note that estimates of persistent symptoms vary considerably across studies, and that the mechanisms responsible remain uncertain. (Frontiers)

Several explanations have been proposed.

There could be persistent organisms that survived treatment or remained inaccessible to antibiotics.

There could be autoimmune or immune-mediated responses.

Co-infections could contribute.

Changes to the microbiome could influence inflammatory signaling through the gut-brain axis.

And another possibility is particularly relevant to the Tulane study:

Pieces of the bacterium may remain after treatment and continue stimulating the immune system. (Frontiers)

That would fundamentally change how researchers think about treatment.

Killing the Bacterium May Not Immediately End the Inflammatory Signal

Antibiotics are designed primarily to kill or suppress bacteria.

But killing an organism does not necessarily make every component of that organism disappear immediately.

Bacteria contain proteins, lipoproteins, DNA and other molecular structures capable of interacting with the immune system.

The Tulane group had previously found that non-viable B. burgdorferi could provoke inflammatory responses and cellular injury in nervous-system tissues. Their 2024 work built on that finding. (Frontiers)

In the new study, the researchers exposed nervous-system tissue to either:

live Borrelia burgdorferi

or

sonicated, non-viable bacterial material.

They then examined inflammatory signaling and cell death.

Both forms could produce biological effects.

That means researchers cannot automatically assume:

dead bacterium = biologically irrelevant bacterium.

A bacterial fragment may no longer be capable of replicating or causing infection in the traditional sense while still containing molecules capable of stimulating inflammation.

Why This Could Matter for Persistent Lyme Symptoms

Imagine two very different biological scenarios after antibiotic treatment.

In the first:

Living Borrelia remain somewhere in the body.

The therapeutic goal would logically involve finding and eliminating those organisms.

But in the second scenario:

The bacteria have been successfully killed, yet bacterial antigens, inflammatory signaling or immune abnormalities remain.

More antimicrobial therapy might not address the primary problem.

The treatment target might instead need to become the host inflammatory response.

The Tulane study explores that second possibility.

The researchers focused on a signaling system called the fibroblast growth factor receptor pathway.

What Are FGFRs?

Fibroblast growth factor receptors—FGFR1, FGFR2, FGFR3 and FGFR4—are cell-surface receptors involved in numerous biological processes, including cell growth, development, repair and signaling.

Because abnormal FGFR signaling is involved in some cancers, pharmaceutical companies have already developed drugs capable of inhibiting these receptors.

Tulane’s previous research suggested another possible role:

FGFR signaling appeared to participate in the inflammatory response of brain immune cells exposed to B. burgdorferi. (Frontiers)

That created a testable hypothesis.

If FGFR signaling is helping transmit the inflammatory response to Lyme bacteria or their remnants, then:

What happens if you block that pathway?

Researchers Studied Brain and Peripheral Nerve Tissue

The investigators used nervous-system tissue obtained from rhesus macaques.

They examined tissue from two important regions:

Frontal cortex

The frontal cortex plays major roles in cognition, attention, working memory, decision-making and executive function.

Dorsal root ganglia

Dorsal root ganglia are clusters of sensory nerve cells located outside the spinal cord and are important in transmitting sensory and pain signals.

This allowed the investigators to examine both the:

central nervous system

and

peripheral nervous system.

The tissues were exposed to live or non-viable B. burgdorferi and then treated with FGFR inhibitors. (Frontiers)

Two FGFR Inhibitors Were Tested

Researchers evaluated two experimental compounds.

PD166866

This compound primarily inhibits FGFR1.

AZD4547

This compound inhibits FGFR1 through FGFR3, with additional activity that may extend to FGFR4.

The investigators then measured inflammatory molecules and apoptosis—the process of programmed cell death. (Frontiers)

The results were encouraging.

Inflammatory Signaling Fell

FGFR inhibition significantly reduced several inflammatory mediators.

Three molecules were particularly important:

CCL2

CXCL8

IL-6

These cytokines and chemokines participate in inflammatory signaling and immune-cell recruitment.

The response varied depending on the tissue, bacterial preparation and FGFR inhibitor.

In frontal-cortex tissue, CCL2 and IL-6 were among the mediators most consistently reduced.

In dorsal-root-ganglion tissue, CXCL8 and IL-6 were particularly responsive. (Frontiers)

This was not merely a change in laboratory inflammatory markers.

Researchers found another important effect.

Cell Death Also Declined

Exposure to B. burgdorferi or its components can provoke apoptosis in nervous-system tissue in the experimental model.

When the FGFR inhibitors successfully suppressed inflammatory signaling, the researchers generally observed a corresponding reduction in apoptosis.

Across the experiments, reductions in at least two major inflammatory mediators usually corresponded with reduced cellular death. (Frontiers)

This suggests that FGFR signaling may sit somewhere upstream in a biological cascade:

Borrelia or bacterial remnants

↓

FGFR-associated signaling

↓

inflammatory cytokine and chemokine production

↓

neural tissue injury / apoptosis

If that pathway is validated in additional research, interrupting it might offer an entirely different therapeutic strategy from simply giving additional antibiotics.

Dead Borrelia May Be an Important Clue

Perhaps the most fascinating aspect of the study is what happened with non-viable organisms.

The researchers had previously demonstrated that fragments of dead B. burgdorferi could generate strong inflammatory responses in nervous-system tissues.

In some experimental settings, the response could be comparable to—or greater than—the response produced by living organisms. (Frontiers)

The 2024 study showed that FGFR inhibition could reduce inflammation produced by these bacterial remnants as well, although the response was not uniform across every tissue sample or inhibitor. (Frontiers)

This matters because fragments or antigens from infectious organisms can sometimes remain in tissues after the organisms themselves are no longer viable.

The paper cites evidence of persistent bacterial antigenic material or DNA after antibiotic treatment in experimental models and in some human Lyme research. (Frontiers)

That does not prove that retained Borrelia fragments cause PTLDS.

But it provides a plausible biological hypothesis worth investigating.

This Could Help Reframe a Major Lyme Debate

The persistent-Lyme discussion has often been framed as a binary argument:

Either the bacteria are still alive

or

the patient should no longer be sick.

Biology may be substantially more complicated.

Several processes could conceivably coexist:

• persistent organisms in some patients
• residual bacterial antigens
• immune dysregulation
• autoimmunity
• altered inflammatory signaling
• neurological injury
• autonomic dysfunction
• microbiome alterations
• co-infections
• consequences of the initial tissue damage

Tulane’s work suggests another question researchers should ask:

What if the infection initiates an inflammatory process that outlasts the infection itself?

That would not make the symptoms psychosomatic.

It would make them post-infectious biology.

The Research Also Fits With Evidence of Neuroinflammation

The Tulane researchers point to previous imaging work showing evidence consistent with glial activation in the brains of some patients with post-treatment Lyme disease.

Glial cells—including microglia—play essential roles in maintaining and defending the nervous system.

But chronically activated glial cells can also produce inflammatory mediators.

Tulane’s investigators therefore propose persistent neuroinflammation as one possible contributor to symptoms such as cognitive problems, fatigue and neuropathy. (Frontiers)

Again, that mechanism has not been established as the explanation for every patient.

But it offers a measurable biological pathway researchers can investigate rather than treating unexplained neurological symptoms as scientifically inaccessible.

One Drug Was Not Universally Effective

An important detail can easily disappear in headlines.

The results were promising—but not perfectly uniform.

For example, the broader FGFR inhibitor AZD4547 significantly reduced inflammatory signaling in tissue exposed to live B. burgdorferi, but its effect against inflammation produced by bacterial remnants was less consistent.

Only one of two frontal-cortex tissue samples and two of three dorsal-root-ganglion samples showed substantial inflammatory suppression in response to remnants under the researchers’ criteria. (Frontiers)

The more FGFR1-specific inhibitor, PD166866, appeared more consistently effective across several experimental conditions.

That variability reinforces an important point:

This is exploratory mechanistic research—not evidence for a ready-to-use treatment protocol.

These Are Not Lyme Drugs

FGFR inhibitors have primarily been explored and developed within oncology.

Blocking the FGFR pathway systemically is not biologically trivial.

FGFR signaling participates in normal cellular processes throughout the body.

Existing FGFR-targeting cancer drugs can have clinically significant adverse effects, and their risk-benefit calculation in cancer may be very different from the calculation for someone with chronic neurological symptoms after Lyme disease.

Nothing in the Tulane research demonstrates that patients with PTLDS should take an FGFR inhibitor.

The study provides proof of principle:

Blocking the pathway reduced Lyme-associated inflammation in experimental nervous-system tissue. (Frontiers)

The next challenge is turning that mechanism into something clinically useful and acceptably safe.

Researchers May Not Need to Use Cancer Drugs Directly

This leads to an intriguing drug-development possibility.

If scientists determine that specific downstream inflammatory signals are primarily responsible for tissue injury, they might not need to broadly inhibit FGFRs.

The Tulane paper identifies molecules such as:

IL-6

CCL2

and

CXCL8

as potential therapeutic targets.

The researchers even suggest that combinations of targeted biologic therapies might eventually be capable of suppressing neuroinflammation without broadly disrupting the entire FGFR pathway. (Frontiers)

That remains hypothetical.

But it is exactly the type of mechanism-driven research the Lyme field needs.

Instead of asking only:

“Which antibiotic should we try next?”

researchers can ask:

“What biological process is producing the patient’s continuing symptoms, and what is the most precise way to interrupt it?”

What the Study Actually Proves

The distinction between an exciting finding and a clinical conclusion is essential.

Tulane demonstrated that:

1. Both live and non-viable B. burgdorferi can provoke inflammatory responses in rhesus nervous-system tissue.

2. FGFR signaling appears to participate in that response.

3. Experimental FGFR inhibitors reduced several important inflammatory mediators.

4. Reducing inflammation was generally associated with reduced apoptosis.

5. The pathway therefore represents a plausible therapeutic target for further investigation. (Frontiers)

The research did not demonstrate that:

1. FGFR activation causes PTLDS in humans.

2. Borrelia fragments are responsible for persistent symptoms in every patient.

3. FGFR inhibitors improve symptoms in people with Lyme disease.

4. These compounds are safe for long-term use in this population.

5. Patients should use an existing FGFR-targeting cancer medication for Lyme disease.

There have not yet been human clinical trials establishing this strategy as a treatment for PTLDS in the research discussed here.

The Bigger Opportunity: Treat the Mechanism, Not the Label

This study points toward a larger transformation that could eventually occur in Lyme medicine.

“Post-treatment Lyme disease” describes a clinical history.

It may not describe a single biological disease state.

Imagine instead categorizing patients according to measurable mechanisms:

Persistent infection phenotype

Evidence suggesting viable organisms remain.

Persistent-antigen phenotype

Microbial material remains and continually stimulates immunity.

Neuroinflammatory phenotype

Activated immune pathways inside the nervous system sustain symptoms.

Autoimmune phenotype

The infection triggers immune activity directed toward the patient’s own tissues.

Autonomic phenotype

The infection or subsequent inflammation disrupts autonomic nervous-system function.

Metabolic phenotype

The illness alters cellular energy production or systemic metabolism.

Patients could have one or several of these processes simultaneously.

That is a much more sophisticated model than assuming every persistent symptom must have the same cause.

This Is Where Lyme Research Should Go

Tulane’s work is compelling not because scientists discovered a Lyme cure.

They did not.

It is compelling because they identified a specific, testable biological pathway connecting exposure to Borrelia with inflammation and neural cell injury—and demonstrated that interfering with that pathway changes the biological outcome.

That creates a research program.

The next questions become clear:

Can the finding be replicated?

Is the FGFR pathway activated in actual PTLDS patients?

Can biomarkers identify those patients?

Are bacterial antigens detectable in affected tissues?

Which inflammatory signals correlate with symptoms?

Can researchers selectively suppress the harmful inflammatory response without impairing healthy FGFR functions?

Does doing so improve cognition, fatigue, pain or neuropathy?

And ultimately:

Can this mechanism become a safe treatment in humans?

Those are answerable questions.

And for a disease field that has spent decades arguing about terminology, turning controversy into experimentally testable biology may be one of the most important forms of progress.

The future of Lyme treatment may therefore extend beyond killing Borrelia.

For some patients, the next therapeutic frontier may be understanding—and stopping—what the infection leaves behind.

The underlying study was published in Frontiers in Immunology in April 2024 and conducted using ex vivo rhesus macaque nervous-system tissue. It was funded by the Bay Area Lyme Foundation and supported by the Tulane National Primate Research Center base grant from the National Institutes of Health. The author reported no commercial or financial conflicts of interest. (Frontiers)

Telos Lyme reports on emerging Lyme and tick-borne disease research. Experimental findings discussed here should not be interpreted as treatment recommendations. FGFR inhibitors have not been established as a treatment for post-treatment Lyme disease syndrome, and prescription treatment decisions should be made with qualified clinicians.