Novel Therapeutic for Duchenne Muscular Dystrophy (DMD)

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DESCRIPTION (provided by applicant): A significant body of literature indicates that Hepatocyte Growth Factor (HGF) via potent and direct anti-fibrotic activity protects many organs from the fibrosis-driven pathology. In addition, HGF has been shown to also promote muscle progenitor cells to proliferate to promote the regenerative capacity of the muscle in response to injury or significant work load. Potentially Refanalin could recapitulate both activities of HGF and promote more efficient repair and prevent fibrosis in the setting of Duchenne Muscular Dystrophy. We have evaluated Refanalin in several models of tissue fibrosis including, lung and liver fibrosis, and in preclinical models of ischemic stroke, hepatic, renal, pulmonary and myocardial ischemia-reperfusion injury including models of liver, kidney and lung transplantation. Treatment with Refanalin was associated with reduced mortality, improved organ function and preservation of tissue architecture. These efficacy data (some presented here) coupled with an excellent safety profile and ideal drugability, makes Refanalin an ideal candidate for evaluation in DMD. We are in a unique position, to test our first in class, small molecule HGF mimetic, in the setting of muscular dystrophy where the "gold standard" of treatment remains only the corticosteroids, which have dose- limiting potentially severe side effects. Refanalin, has been dosed in man; phase I dose-escalation safety and pK studies having been completed in healthy volunteers, and it currently being evaluated in a phase IIa pK, safety study in dialysis patients with the intent to enter larger scale phase IIb efficacy studies in kidney patients by first quarter 2009. PUBLIC HEALTH RELEVANCE: Our lead molecule, Refanalin, which has advanced to clinical trial in kidney patients, is a small molecule-HGF mimetic. Extensive studies in the laboratory have shown that Refanalin will exert potent anti-fibrotic effects in many disease settings. These results in conjunction with the possibility that Refanalin will mimic HGF and promote satellite cell activation- potential improving on muscle regeneration, makes Refanalin an attractive possible therapy for the severely debilitating disease of young boys, Duchenne Muscular Dystrophy.