# Engineered probiotic for the treatment of autoimmune diseases

> **NIH NIH R01** · BAYLOR COLLEGE OF MEDICINE · 2024 · $675,152

## Abstract

PROJECT SUMMARY
 Approximately 50 million people suffer from one or more autoimmune diseases in the US alone. Over the
last decades, the discovery of biologics has considerably improved the care for patients with autoimmune
diseases. However, current treatments require weekly or more frequent injections and this can lead to missed
doses and to poor patient compliance, especially in the younger population, resulting is inconsistent or sub-
therapeutic drug levels. Since many of the therapeutics on the market or being developed to treat rheumatoid
arthritis (RA), multiple sclerosis, and other T lymphocyte-mediated chronic autoimmune diseases are biologics,
we propose a novel bioengineering approach for the non-invasive delivery of recombinant peptides in
autoimmune diseases. More specifically, we propose to produce an immunomodulatory peptide by a probiotic
for oral administration to treat RA.
 As our immunomodulator, we have chosen a recombinant analog of ShK, a small venom peptide that blocks
Kv1.3 channels and thus inhibits the activation of human and rat effector memory T lymphocytes. As a probiotic,
we have selected Lactobacillus reuteri LJ01, a well-characterized probiotic that survives transit through the
gastrointestinal tract. In preliminary work, we have introduced an ShK analog in L. reuteri to generate LrS235
that secretes a functionally active peptide upon induction, resulting in the block of Kv1.3 channels and the
inhibition of human TEM cell proliferation in vitro and in a reduction of clinical severity in a small pilot trial using
the collagen-induced arthritis rat model of RA.
Through this project, we will define the pharmacokinetics, biodistribution, and efficacy of ShK-235 produced by
LrS235 in preventing and treating rat models of RA (Specific Aim 1) and we will define and optimize the
efficacy and safety of our probiotic based gut delivery (Specific Aim 2). At the end of this project, we will have
established proof-of-concept for a new therapeutic strategy for the treatment of RA and other autoimmune
diseases mediates by effector memory T lymphocytes through the oral delivery of a probiotic engineered to
secrete an immunomodulatory Kv1.3 blocking venom peptide.

## Key facts

- **NIH application ID:** 10812311
- **Project number:** 5R01AI173318-02
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** ROBERT A BRITTON
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $675,152
- **Award type:** 5
- **Project period:** 2023-03-20 → 2028-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10812311

## Citation

> US National Institutes of Health, RePORTER application 10812311, Engineered probiotic for the treatment of autoimmune diseases (5R01AI173318-02). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10812311. Licensed CC0.

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