Novel Therapeutic for Amyotrophic Lateral Sclerosis (ALS)

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DESCRIPTION (provided by applicant): Literature indicates that HGF via its cytoprotective and tissue-regenerative activities protects a number of organs against traumatic and/or ischemic injury and fibrotic/degenerative disease. We have evaluated the effects of BB3/Rf in preclinical models of ischemic stroke, hepatic, renal, pulmonary and myocardial ischemia-reperfusion injury including models of hepatic, renal and lung transplantation. Treatment with BB3/Rf was associated with reduced mortality, improved organ function and preservation of tissue microarchitecture. These efficacy data (not presented here) and the efficacy of BB3/Rf to attenuate spinal cord injury as described in the preliminary results section, coupled with an excellent safety profile and ideal drug ability characteristic makes BB3/RF an ideal candidate for evaluation in other indications where HGF has shown efficacy, such as ALS. We are in the unique position to test out small molecular weight HGF mimetic in the setting of ALS, where various nueorotrophic factors have failed in the clinic, likely due in part to the extreme difficulty of adequately delivering such macromolecular, polypeptides, which will not cross the blood-brain barrier, to the CNS. BB3/RF will not have such limitations. PUBLIC HEALTH RELEVANCE: Recently HGF has demonstrated excellent efficacy in a mouse model of ALS. In this proposal, we are poised to determine if our small molecule, HGF mimetic BB3/Rf will prove similarly efficacious. If so, further studies could bring BB3/RF to the clinic as a possible therapy for ALS, a devastating disease with significant unmet medical need.