Conference Proceeding

The uses of mitochondrial specific protonophore, MP101, as a broad spectrum agent for neuromuscular and neurodegenerative disorders

Dr. John G. Geisler

Although mitochondrial dysfunction has been associated with a number of neurodegenerative disorders, currently, there are no “disease modifying”mitochondrial drug treatments. MP101, an oral brain penetrant, mitochondria-specific protonophore that increases energy expenditure, cAMP, CREB, induces neurotrophin/myokine BDNF, lowers cellular stress (ROSs)/mTOR, and improves calcium handling at weight neutral/preserving doses,may have the merit as a once-per-day treatment for a host of insidious diseases. In representative models of Parkinson’s,Alzheimer’s, Huntington’s, epilepsy, TBI, hearing loss, Duchenne Muscular Dystrophy, Optic Neuritis, and Multiple Sclerosis, under chronic oral administration, we have demonstrated that MP101 provided a disease modifying effect. Although these diseases are genetically unrelated and some with no known genetic cause, it appears that improving mitochondrial resilience with MP101 may provide ubiquitous protective pharmacology for a spectrum of insidious diseases, beyond what is shown here, including metabolic disorders. BDNF has anti-diabetic qualities and the pharmacology of MP101 should improve insulin sensitivity even at these weight neutral doses. Since MP101 is a weak acid and “acids go to base”, the drug specifically targets the mitochondria, the only organelle within the cell with a pH basic environment. The MOA of this broad neuroprotection stems from the unique pleiotrophic effects of modulating the mitochondrial membrane potential andthereby the entire organelle’s physiology with a protonophore. The actions are initially non-genomic vs. a protein pathway, however this action results in a cascade of mitochondrial/cellular remodeling in favor of neuroprotection. The fact that this organelle is highly evolutionarily conserved, there are considerable advantages that predict strongtranslation, precisely our next step now with the completion of the GLP IND enabling studies. Phase I begins in 1Q18 in NHV, with Huntington Disease, DMD and Optic Neuritis as our following Phase II indications.Success here, will open a new door and a new platform to treat truly unmet medical needs.

Published: 17 October 2017


Copyright: © 2017 Dr. John G. Geisler. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.