# A novel therapeutic for Lyme arthritis based on a secretory leukocyte protease inhibitor

> **NIH NIH R41** · L2 DIAGNOSTICS, LLC · 2024 · $299,933

## Abstract

PROJECT SUMMARY/ABSTRACT
 Lyme disease (LD), the most common tick-borne disease in the United States, is caused by a spirochete,
Borrelia burgdorferi. An estimated 500,000 people are diagnosed and treated each year. Antibiotic therapy is mostly
successful in cases diagnosed in the early stage of the infection. However, in some patients, early B. burgdorferi
infection is asymptomatic and Lyme arthritis (LA) is the primary manifestation of long-term LD, which usually occurs
months after the tick bite. LA is the leading cause of Lyme disease-associated morbidity, affecting around one third of
B. burgdorferi-infected individuals. Symptoms of LA include intermittent or persistent attacks of joint swelling and
pain that can lead to permanent joint dysfunction and debilitation. Most patient respond to a 30-day course of oral or
IV antibiotic therapy. However, in a small percentage of LA patients, arthritis persists after antibiotic therapy and can
last for months or several years. Distinct from LA, research has shown that up to 34% of Lyme patients have Post
Treatment Lyme Disease Syndrome (PTLDS). Symptoms include fatigue, pain, joint and muscle aches, and cognitive
decline, with an onset ranging from months to years. Long-term antibiotic therapy has not been proven to be beneficial
for PTLDS. Therefore, better therapeutic agents are urgently needed to resolve both LA and PTLDS.
 A human secretory leukocyte protease inhibitor (SLPI) was identified as binding to B. burgdorferi from the
BASEHIT yeast display library of 3,336 human exoproteins. SLPI is an evolutionarily conserved, multi-functional
protein. SLPI expression inhibits neutrophil activity and the NF-κB pathway in macrophages, leading to an overall
anti-inflammatory effect. A high percentage of neutrophils and macrophages have been observed in the synovial fluid
of LA patients during active LA and post-treatment LA respectively. SLPI also has broad-spectrum antibacterial,
antifungal, and antiviral activities. Using a SLPI knockout mice, our preliminary data showed a significantly higher B.
burgdorferi infection load and severe swelling and synovitis in the tibiotarsal joints of SLPI knockout mice in
comparison to the WT mice. The data indicate that SLPI expression suppresses the B. burgdorferi infection load and
inhibits the development of murine Lyme arthritis.
 The prior knowledge of SLPI and our preliminary data form the foundation of our hypothesis that therapeutic
dosing of SLPI will significantly mitigate human LA. This proposal aims to show the feasibility of that in the murine
LA model. Our long-term product goal is a novel secretory leukocyte protease inhibitor (SLPI) based therapeutic
indicated for advanced Lyme disease, including both LA and PTLS.

## Key facts

- **NIH application ID:** 11008266
- **Project number:** 1R41AI186833-01
- **Recipient organization:** L2 DIAGNOSTICS, LLC
- **Principal Investigator:** Erol Fikrig
- **Activity code:** R41 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $299,933
- **Award type:** 1
- **Project period:** 2024-07-08 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11008266

## Citation

> US National Institutes of Health, RePORTER application 11008266, A novel therapeutic for Lyme arthritis based on a secretory leukocyte protease inhibitor (1R41AI186833-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/11008266. Licensed CC0.

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