Discovery of Oligodendrocyte Stimulators

DESCRIPTION provided by applicant Up to of low birth weight preterm infants manifest some form of periventricular white matter injury PWMI making it the most common form of brain injury affecting premature infants In the US infants per year are born at risk for PWMI and about children per year will develop PWMI World wide infants will be born each year at risk for PWMI and about children per year will develop PWMI Oligodendrocytes OLs are the myelinating cells of the central nervous system and play a critical role in white matter formation It is believed that loss and impaired differentiation of
Pre oligodendrocytes PreOLs which are proliferative cells that develop into myelinating OLs plays a major role in PWMI causation Presently there are few pharmacological approaches that specifically target PreOLs resulting in increased proliferation of these cells and increased brain myelination To address this short coming Dr Scott Rivkees University of Florida used high throughput screening to identify compounds that would stimulate PreOL proliferation These initial studies of compounds identified diazoxide as a stimulator of PreOL proliferation and showed that this compound promotes myelination in a murine model of PWMI However diazoxide was not completely effective in preventing PWMI leading us to look for other compounds that are potentially even more effective than diazoxide Dr Rivkees thus developed small molecule derivatives of diazoxide that were tested for their ability stimulates the proliferation of PreOLs These studies identified compounds that stimulated PreOL proliferation of which designated lead compounds were significantly more potent than diazoxide Medosome Biotec LLC a Florida based small business and its research partner at the University of Florida Dr Rivkees postulate these lead compounds have the potential to be effective new therapeutics for disorders of myelination In these Phase I STTR studies the team proposes to assess the toxicity and myelination potential of our lead compounds We will Evaluate myelination in brain slices Assess in vivo toxicology and myelination potential The long term goal of this work is to develop and commercialize novel therapeutic agents for the treatment of white matter injury in premature infants and other disorders of myelination This STTR award will link scientists at Medosome LLC and Dr Rivkees University of Florida who is a leading expert in the area of white matter injury

PUBLIC HEALTH RELEVANCE Loss of Pre oligodendrocytes PreOLs which are proliferative cells that develop into myelinating OLs play a major role in white matter injury causation Presently there are few pharmacological approaches that specifically target PreOLs resulting in increased proliferation and differentiation of these cells and increased brain myelination The goal of this work is to develop novel therapeutic agents for the treatment of white matter injury in premature infants and other disorders of myelination