10153 – Treatment of Fungal-Associated Irritable Bowel Disease Using IL-1 Inhibitors

  • Method to identify and treat IBD patients harboring specific C. albicans strains with IL-1 inhibitors

Abstract
Background & Unmet Need

  • Intestinal fungi play an important role in regulating mucosal immunity as a highly immunoreactive component of the microbiota
  • Deep sequencing-based assays of the gut mycobiome have revealed consistent evidence for “fungal dysbiosis” as a hallmark of inflammatory bowel disease (IBD)
  • Candida is the most prevalent fungal genus, and its relative abundance is consistently increased in several IBD cohorts based on fecal sequencing
  • However, it is currently unknown whether fungi play an essential role in directing mucosal immunity or disease outcomes
  • Unmet Need: Methods to probe the mycobiome at the fungal strain and patient-specific level to inform potential mycobiome-targeted therapies for IBD

Technology Overview

  • The Technology: Method to identify and treat IBD patients harboring specific C. albicans strains with IL-1 inhibitors
  • Using a proprietary platform that combines high-resolution sequencing, culturing, genomics, and in vitro and in vivo models, the inventors identified opportunistic C. albicans strains that dominate the colonic mucosa of ulcerative colitis (UC) patients
  • The Discovery: C. albicans strains that secrete the toxin candidalysin drive intestinal inflammation through an IL-1β dependent manner
  • PoC Data: IL-1R blockade using an anti-IL-1R antibody dramatically reduced neutrophil recruitment, inflammatory Th17 cell accumulation and colonic inflammation in C. albicans colonized mice

Technology Applications

  • Method for identifying IBD patients who may benefit from anti-IL-1 or antifungal therapies
  • Platform for further studying the impact of the mycobiota on immunity and disease pathogenesis

Technology Advantages

  • Anti-IL-1 monoclonal antibodies are already approved for other indications
  • Provides a precision medicine approach to identify IBD patients who are most likely to benefit from anti-IL-1 treatment

Publications

  • Li et al. “Immune regulation by fungal strain diversity in inflammatory bowel disease.”Nature. 2022.

Patents

  • Provisional Filed

Contact Information

Name : Brian J. Kelly

Email : bjk44@cornell.edu

Phone : 646-962-7045