Enzyme Therapy For Non-Alcoholic Steatohepatitis (NASH) And Related Disorders
Background
NASH is a disease of the liver characterized by inflammation, damage to hepatocytes and compromise of liver function that may progress to an irreversible stage. Typically, NASH and other related Nonalcoholic Fatty Liver Diseases (NFLD), involve hepatic inflammation with fat accumulation and mimics alcoholic hepatitis in patients who seldom or never consume alcohol. Additionally, NASH involves the development of histologic changes in the liver comparable to those induced by excessive alcohol intake including macrovesicular and/or microvesicular steatosis, lobular and portal inflammation, occasionally with fibrosis and cirrhosis. NASH is commonly associated with hyperlipidemia, obesity and type II diabetes mellitus, and has been frequently associated with excessive fasting, jejunoileal bypass, total parental nutrition, chromic hepatitis C, Wilson's disease and adverse drug effects from corticosteroids, calcium channel blockers and high dose synthetic estrogens. Currently there is no established therapy for NASH. Weight loss is commonly prescribed since NASH is often found in obese patients. NASH develops in at least 10-20% of obese adolescents and adults and in 5-10% of those that are overweight. It is estimated that there are over 500,000 people in the US with NASH or some form of NFLD. Current market estimates to treat this disorder are determined to be approximately $500 million per year.
Current Invention
The technology presented here, developed by Dr. Gregory Grabowski at Cincinnati Children's Research Foundation (CCRF), relates to the use of a lipid hydrolyzing protein, lysosomal acid lipase (LAL), for the treatment and/or prevention of NASH and related disorders. In laboratory studies, LDLR -/- mice fed a high fat/high cholesterol diet develop fatty liver transformations, including micro- and macrovesicular fatty changes and inflammatory cell infiltration, resembling NFLD. Intravenous administration of exogenous LAL led to significant reductions of inflammation and microvesicular fat and a disappearance of macrovesicular fat deposits in the liver of these animals. Control mice receiving LAL showed no adverse effects. An effective dose of human LAL can be administered on a regular basis by the usual exogenous routes or by endogenous routes from vectors expressing LAL in hepatocytes or hematopoietic or other stem cells in a continuous or controlled manner. The LAL technology represents an opportunity to develop and market a treatment for a common disorder where no current therapy exists and for a disease that accompanies many other common disorders in children and adults such as obesity, diabetes and hepatitis C. Outcomes can easily be assessed with serum or tissue biomarkers, biopsies or other convenient markers. The treatment allows the effected hepatocytes to return to some degree of normal activity thus providing patients with the return of several physiologic functions compromised by NASH. A provisional patent application has been filed and research on this technology continues.
Objective
CCRF is seeking a corporate partner for the continued research into the treatment of NASH and related disorders with LAL and to develop and market a therapy using this technology.
Contact
For further information concerning this technology and/or to receive confidential data please contact:
Joseph D. Fondacaro, PhD
Director, Office of Intellectual Property & Venture Development
Cincinnati Children's Research Foundation
3333 Burnet Avenue, MLC 7032
Cincinnati, Ohio 45339-3039
Phone: 513-636-7695
Fax: 531-636-8453
Email: jdfonda@cchmc.org
