Matrix Metalloproteinase Inhibitors to Treat Fatty Liver Disease
Inventors: Marsha Moses, Mark Puder
Invention Types: Therapeutics
Research Areas: Internal Medicine, Metabolic Disease
Keywords: Hepactic, New Indication/Use, Obesity, Small Molecule/DrugFor More Information Contact: Khunkhun, Rajinder
Investigators at Children's Hospital Boston have discovered a novel use of matrix metalloproteinase inhibitors (MMPIs) to treat fatty liver disease. Using a mouse model, they showed that administration of MMPIs prevented the development of fatty liver disease in animals given a diet associated with fat-induced liver damage. Livers of control and experimental animals were evaluated both physically and chemically, and while the animals on the high-fat diet alone developed abnormal liver features, those treated with MMP inhibitors did not. Both the physical features of the liver and chemical liver marker levels in the MMP-treated animals were normal, indicating not only that the MMP inhibitor prevented the development of fat particles in the organ but also protected the cellular function of the hepatocytes.
Fatty liver disease is the precursor to major liver damage, including liver inflammation, scarring, cirrhosis and liver failure. The major causes of fatty liver disease are obesity and diabetes, both of which are on the rise in the United States and elsewhere. The number of people with excessive fat accumulation in the liver is increasing and is estimated to be 30% of the population in both Western European countries and the United States. Up to 10% of this population, 3% of all adults, will develop serious liver disease, including cirrhosis. Last year 60,000 deaths in the United States resulted from liver failure, and there are currently over 17,000 people waiting for a liver transplant.
Small molecule treatment for fatty liver disease associated with obesity
There is currently no treatment for fatty liver disease other than weight loss or liver transplant. This technology has the potential to prevent and treat fatty liver disease, a precursor to liver failure, and thereby reduce liver-related morbidity. This small molecule therapy has the potential to be adopted as the standard of care due to the unmet medical need in this area, representing the potential for a large-market business opportunity.
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Key Publications: Inhibition of matrix metalloproteinases increases PPAR-alpha and IL-6 and prevents dietary-induced hepatic steatosis and injury in a murine model.|Alwayn IP, Andersson C, Lee S, Arsenault DA, Bistrian BR, Gura KM, Nose V, Zauscher B, Moses M, Puder M.|Am J Physiol Gastrointest Liver Physiol. 2006 Dec;291(6):G1011-9.| US Patent Application number 11/997,002
Related Publications: A critical role for matrix metalloproteinases in liver regeneration.|Alwayn IP, Verbesey JE, Kim S, Roy R, Arsenault DA, Greene AK, Novak K, Laforme A, Lee S, Moses MA, Puder M.|J Surg Res. 2008 Apr;145(2):192-8.