Mitofusin agonists to prevent Charcot-Marie-Tooth disease 2A

Mitofusin agonists to prevent Charcot Marie Tooth diseaseA Gerald W Dorn IIMD Mitochondria in MotionIncWashington University in St Louis School of Medicine AbstractCharcot Marie ToothCMTdisease typeA is an incurableprimarily pediatricautosomal dominant neuromuscular degenerative disease caused by mutations in the mitofusinMFNgeneThere are currently no disease altering treatmentsMitochondria in MotionIncwill develop and produce investigational first in class small molecule mitofusin agonistsunder an FDA approved INDto treat CMT A and other neurological diseasesMitofusin agonists enhance mitochondrial fitnessmetabolismand trafficking within cellsthus improving homeostatic functioning and injury responses of neurons adversely impacted by MFNgenetic mutationsHerewe hypothesized that activating endogenousgenetically normal MFNand MFNwill reverse dominant inhibition by CMT A MFNmutants of neuronal mitochondrial fusion and traffickingthus delaying or preventing CMT A induced neuromuscular degenerationOur immediate goals are to refine our lead mitofusin agonist for in vivo administrationSAand to provide proof of concept for in vivo mitofusin agonist efficacy in a mouse model of aggressive CMT ASAto support our preclinical data in CMT A patientderived cellsWe will fill an unmet healthcare need and build a commercial enterprise to serve theAmericans with CMT A and the andgtAmericans suffering from other neurodegenerative diseases characterized by mitochondrial degenerationincluding CMT typeamyotrophic lateral sclerosisand Huntington s diseaseOur deliverable in thisyear Phase I STTR will be a mitofusin agonist sready for STTR Phase II IND enabling studies in CMT A and validation in an expanded number of orphan diseasesin preparation for anticipated first in human trials Lay abstractCharcot Marie Tooth disease typeACMT Ais a tragic genetic childhood condition that causes slowly progressive weakness and atrophy of muscles in the forearmhand lower legand feetultimately leading to partial and life long disability from young adulthoodDespite having identified the genetic cause of this disease overyears agothere is neither a cure nor any way of delaying or ameliorating the diseasea diagnosis is a sentence to life in a wheelchairWe developed a new class of drugs called mitofusin agonists that correct abnormalities in cultured mouse and human cell models of CMT ANowthe biotechnology research and development company we recently formedMitochondria in MotionIncwill finalize modifications to our lead compoundmaking it suitably andquot drug likeandquotWe will prove the concept that mitofusin agonists can prevent or delay CMT A in a humanized mouse modelbringing us closer to first in human trials