Nitrate Chimeras: A New Class of Disease Modifying Agents for the Treatment of Alzheimer's Disease

The primary goal of my PhD was to provide a mechanistic understanding of observed effects of nitrate chimeras, a novel class of drugs developed by Dr. Gregory Thatcher for treatment of neurodegenerative diseases such as Alzheimer’s disease (AD). An example of this class, GT-1061, has received FDA approval for clinical trials. With support from the NIA, we refined and redesigned novel compounds from the drug class, with preliminary data showing promise in both culture and animal models of AD. This project deepened the understanding of the observed effects of methiazole-based nitrate chimeras by investigating mechanisms of action in culture, tissue and animal models of AD and determined the effect of nitrate chimeras on classic AD pathophysiology. This work also supported the entry of two optimized novel compounds into clinical trials and identified novel mechanisms of action of potential utility in the AD drug development field.