Selection and Development of a Lead Biologic for Treating Mitochondrial Disorders

Project Summary Abstract Mitochondrial dysfunction causes mitochondrial diseases and is tightly linked to aging and neurodegenerative disorders such as Parkinsonandapos s and Alzheimerandapos sRecent discoveries support that mitochondrial dysfunction can be overcome to treat age related declineCyteGenandapos s hypothesis is that exercise induces the secretion of bloodborne proteins that act systemically to stimulate removal of damaged mitochondria and enrichment of healthy mitochondriamitochondrial fitnessThe companyandapos s goal is to identify these proteins to develop into biologics that would serve as a platform to treat the myriad of diseases associated with mitochondrial dysfunctionThe discovery platform builds on existing work that exercise reversed mitochondrial dysfunction in a mouse model for mitochondrial diseaseIn this applicationthe candidate factors are tested in a cell based mitochondrial respiration assay in Aimand evaluated known agonists of mitochondrial biogenesisbezafibrate and the glitazonesPPAR agonistsmetformin and AICARAMPKand resveratrolSirtThe results will be a rank ordering of each candidate factor based on their ability to improve respirationIn Aimfalse positives will be eliminated through commonplace assays to assess mitochondrial morphological analysesmtDNA copy numberand expression of mitochondrial quality control proteinsThese data will winnow the list to a lead biologic candidate for Phase II development in pre clinical models and translation into clinical trials Project Narrative Mitochondrial dysfunction causesor contributesto many pathological conditions including cancercardiomyopathiesneurodegenerationagingand rare neuromuscular disordersThis application proposes to evaluate exciting new technologies for discovering interventions that can restore mitochondrial function to successfully treat these diseases