Antifungal Therapy for Treatment of Hirschsprung-Associated Enterocolitis

Tech ID: fry000784

 

Introduction

Hirschsprung-associated enterocolitis (HAEC) remains the most frequent complication in children with Hirschsprung disease resulting in frequent hospitalizations and is the primary cause of mortality in this population. However, the underlying biological mechanisms are poorly understood. A microbial role in the development of HAEC has been suspected since it was first described over 50 years ago; although no specific organisms have yet been identified. Currently, most infants with HD are treated with colon pull through surgery that removes the aganglionic portion of colon and re-establishes fecal continuity in the first weeks of life. Surgical results are satisfactory for most children, however 20-30% of children experience a serious and potentially life-threatening enterocolitis after surgery

Dr. Frykman discovered that Hirschsprung patients with a history of HAEC had increased amounts of a species of fungus (4-fold) in their stool compared with children that never had HAEC, opening the possibility for the development of new antifungal treatments.

 

Technology Description

The inventor has identified a certain species of fungus that is more abundant in pediatric Hirschsprung patients with a history of HAEC by 18S ITS rRNA Next Generation Sequencing of fecal fungi of patients and statistical analysis. He also developed a qPCR-based diagnostic test for specific fungi for HAEC patients. The test is in research validation stage. Clinical validation will be needed. The invention can be used towards developing a new use for existing anti-fungal drugs.

 

Advantages/Novelty

•       This invention is the first diagnostic and rational therapeutic approach to treat children with HAEC.

•       Current HAEC treatment methods include broad-spectrum antibiotic therapy, rectal wash outs with saline and cromoglycate. These therapies can be effective initially, however often they fall far short especially in cases of recurrent enterocolitis. Furthermore, when these non-specific approaches to treat this poorly understood condition fail, the physician or surgeon has few options.

 

Applications

• Companies with proprietary anti-fungal agents and an interest in orphan disease can collaborate with Dr. Frykman by providing the drug and clinical trial support to further advance their composition for this indication. 

• Specialty pharmaceutical companies can provide formulation and dosing expertise to repurpose generic anti-fungal agents.

• Companies interested in developing diagnostic tests for HAEC can collaborate with Dr. Frykman to further validate his qPCR-based test.

 

Intellectual Property

US 15/461,349 pending.

 

Publications

Frykman et al. Characterization of Bacterial and Fungal Microbiome in Children with Hirschsprung Disease with and without a History of Enterocolitis: A Multicenter Study. PLoS One. 2015, 10(4):e0124172. [LINK]

 

Patent Information:
For Information, Contact:
Wenyue Du
Senior Associate - IP Management & Licensing
310-423-2241
wenyue.du@cshs.org
Inventors:
Philip Frykman
Keywords:
GI Disorders