Chitinase 3-like-1 (CHI3L1) as Biomarker for Hermansky-Pudlak Pulmonary Fibrosis

Overview

Hermansky-Pudlak syndrome (HPS) is a group of autosomal recessive disorders caused by mutations that affect the function of lysosome-related organelles (LROs). All HPS patients have oculocutaneous albinism with visual impairment, and many have blood platelet dysfunction with bleeding disorder. HPS-1 and HPS-4 patients, who have mutations of BLOC-3 (biogenesis of lysosome-related organelles complex 3), also develop pulmonary fibrosis, usually in the fourth or fifth decade of life. Because HPS fibrosis is progressive and untreatable, it is the leading cause of death in these patients. We have discovered a biomarker for HPS lung disease and disease progression.

Market Opportunity

Currently, there is no way to predict those HPS patients for whom lung involvement is imminent, or which cases will progress most rapidly. Thus, there is a need for a biomarker for HPS lung disease and disease progression, as well as a way to define the mechanisms by which LRO dysfunction lead to lung injury and progressive fibrotic response.

Innovation and Meaningful Advantages

We have discovered a biomarker for HPS lung disease and disease progression: the protein chitinase 3-like-1 (CHI3L1), which plays a protective role by ameliorating cell death and stimulating fibroproliferative repair. As BLOC-3 HPS is associated with higher levels of CHI3L1, CHI3L1 can differentiate those HPS patients who will develop fibrosis from those who will remain fibrosis-free and predict disease progression. We have also validated two therapeutic interventions for HPS pulmonary fibrosis, which target the trafficking and effector functions of the CHI3L1 receptors IL-13Rα2 and CRTH2. The therapeutic drugs can be used separately or simultaneously.

Collaboration Opportunity

We are interested in exploring 1) startup opportunities with investors in the drug delivery space; 2) research collaborations with leading pharmaceutical companies; and 3) licensing opportunities with drug delivery companies.

Principal Investigator

Jack A. Elias, MD
Frank L. Day Professor of Biology, Professor of Medicine
Brown University

IP Information

US Patent 2014/0200184A1, Issued July 17, 2014. 

Publications

Zhou Y, He CH, Herzog EL, Peng X, Lee C-M, Nguyen TH, Gulati M, Gochuico BR, Gahi WA, Slade ML, Lee CG, and Elias JA. Chitinase 3–like–1 and its receptors in Hermansky-Pudlak syndrome–associated lung disease. Journal of Clinical Investigation. 2015 June 29;125(8):3178-3192. doi: 10.1172/JCI79792.

 

Contact

Andrew Bond, PhD
Senior Director of Business Development
andrew_bond@brown.edu
Brown Tech ID 2283J
Patent Information: