Treatment for alcoholic liver disease

Award Information
Agency: Department of Health and Human Services
Branch: N/A
Contract: 1R43AA019876-01
Agency Tracking Number: AA019876
Amount: $238,482.00
Phase: Phase I
Program: SBIR
Awards Year: 2010
Solicitation Year: 2010
Solicitation Topic Code: NIAAA
Solicitation Number: PHS2010-2
Small Business Information
ANGION BIOMEDICA CORPORATION
ANGION BIOMEDICA CORP, 1050 Stewart Ave., GARDEN CITY, NY, 11530
DUNS: 053129065
HUBZone Owned: N
Woman Owned: N
Socially and Economically Disadvantaged: N
Principal Investigator
 BERT OEHLEN
 (516) 326-1200
 BOEHLEN@ANGION.COM
Business Contact
 ITXHAK GOLDBERG
Phone: (516) 326-1200
Email: igoldberg@angion.com
Research Institution
N/A
Abstract
DESCRIPTION (provided by applicant): Liver fibrosis is a form of scar formation that is found in almost all patients with chronic injury to the liver. Over time it frequently progresses to cirrhosis, an end-stage lethal disease which is the seventh leading cause of death in the United States and afflicts hundreds of millions of people worldwide. Alcohol intake remains the most important cause of liver cirrhosis in Western countries. Alcoholic liver disease can be divided in various stages of development: (1) mild alcoholic liver injury, (2) steatosis, (3) alcoholic hepatitis, (4) alcoholic liver fibrosis and (5) cirrhosis. Although several pharmacological therapies have been tried in patients with alcoholic liver disease, none of the therapeutics so far has shown consistent improvement in the course of alcoholic liver damage and there remains a major unmet medical need for effective therapies. There is a significant body of evidence implicating a requirement for All Trans Retinoic Acid (ATRA) for normal liver function and in liver regeneration. ATRA administration can prevent and reverse the course of liver fibrosis in animal models. Several studies have shown that inhibition of certain cytochrome P450 enzymes in vivo can boost endogenous ATRA levels and result in retinoid-like activity in dermatological and oncological animal models. The cytochrome P450 enzyme retinoic acid 4-hydroxylase is thought to be the key enzyme involved ATRA catabolism. In our preliminary data, we show that an inhibitor of retinoic acid 4-hydroxylase shows activity in a mouse model of TAA-induced liver fibrosis in mice, thus establishing a novel proof of concept for their potential use as therapeutics for liver fibrosis. Our long-term goal is the development of small molecule inhibitors of retinoic acid 4-hydroxylase as potential therapeutics for alcoholic liver disease. The objective of this application is to identify such inhibitors and evaluate them in two clinically relevant animal models of liver fibrosis. PUBLIC HEALTH RELEVANCE: Liver fibrosis is a form of scar formation that is found in almost all patients with chronic injury to the liver caused by sustained immoderate alcohol consumption. Over time it frequently progresses to cirrhosis, an end- stage lethal disease which is the seventh leading cause of death in the United States and afflicts hundreds of millions of people worldwide. There is no therapeutic that shows consistent improvement in the course of alcoholic liver damage and there remains a major unmet medical need for effective therapies. There is a significant body of evidence implicating a requirement for All Trans Retinoic Acid (ATRA) for normal liver function and in liver regeneration. We intend to develop of small molecule inhibitors of retinoic acid 4- hydroxylase that can elevate the body's ATRA levels as a potential therapeutic for alcoholic liver disease.

* information listed above is at the time of submission.

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