Problem
Parkinsonian disorders are the second most common neurodegenerative disease in the United States, with no definitive treatment option available. Exposure to the metal manganese has been shown to be a major cause of parkinsonism.
Solution
Dr. Somshuvra Mukhopadhyay and his team have developed a pharmaceutical method for the management of manganese-induced parkinsonism by increasing the expression of a cell-surface manganese efflux transporter, SLC30A10. The treatment activates hypoxia-inducible factors (HIF) to increase the expression of SLC30A10 in the liver. This enhances manganese excretion, lowering body manganese levels and thereby alleviating parkinsonism.
This treatment has utility for those who have been exposed to high levels of manganese, or who have a genetic predisposition to manganese-associated parkinsonism. Disease-causing mutations trap SLC30A10 in the endoplasmic reticulum, inhibiting manganese efflux and inducing manganese toxicity. Testing in cells and mice identified prolyl hydroxylase inhibitors for use as potential therapeutic agents for the management of parkinsonian disorders caused by elevated manganese levels, and this represents the first definitive treatment for a parkinsonian disorder.
About the inventor
Dr. Mukhopadhyay is an Associate Professor in the College of Pharmacy and an Alan W. Hamm Centennial Fellowship in Pharmacy at UT Austin, with primary research interests in neuroscience, cell biology, infectious diseases, and drug development/discovery. He has authored/or co-authored dozens of technical/journal publications and has received numerous awards over the past twenty years. The focus of his work has broad applicability in gene mutations as a cause of parkinsonian disorders and in how bacteria/toxins cause diseases.
