British pharmaceutical firm Mission Therapeutics will test its potent, selective USP30-targeted inhibitors in stem cell-derived Parkinson’s disease models, as part of research funded by the Michael J. Fox Foundation for Parkinson’s Research (MJFF).
Cells maintain healthy mitochondria — the cell’s power generators — by degrading damaged mitochondria in a process known as mitophagy. Defective mitophagy has been linked to Parkinson’s disease. USP30, a deubiquitinase (DUB) located in the mitochondria, has been shown to control mitophagy under normal conditions. However, in neurons affected by Parkinson’s, altered USP30 signaling can lead to the toxic accumulation of mitochondria, which damages neuronal cells.
Mission Therapeutics has developed potent, selective inhibitors of USP30 and is exploring their potential for treating both Parkinson’s and cancer. Working with a research group led by University of Oxford Professor Richard Wade-Martins, the company will now test its USP30 inhibitors in induced pluripotent stem sells (iPSC) derived from patients with sporadic and familial Parkinson’s.
“USP30 is one of the more promising DUBs associated with mitophagy, in terms of published data and feasibility of compound development,” Shalini Padmanabhan, PhD, associate director of research programs at the New York-based MJFF, said in a press release. “We hope that this collaboration between Mission Therapeutics and Oxford Parkinson’s Disease Centre will promote our understanding of the mechanisms and consequences of USP30 inhibition in Parkinson’s disease.”
Neither the foundation nor the university disclosed the amount of MJFF’s grant.
“Receiving funding from the Michael J. Fox Foundation is a great accolade, recognizing the quality of the research being done by Mission Therapeutics and Prof. Wade-Martins and his group. The collaborative study will provide key data that will guide the clinical development strategy of our USP30 inhibitor program,” said Michael Koslowski, executive vice-president of research and development at Mission Therapeutics. “We are working hard to find new ways in which to tackle this difficult disease, which is especially highlighted during this World Parkinson Awareness week, for patients and their families.”
Parkinson’s is a long-term degenerative disorder of the central nervous system. No test or biomarker capable of identifying Parkinson’s is currently available, so the misdiagnosis rate can be substantially high. Recent estimates indicate that the disease affects nearly one million Americans, and more than five million people worldwide.