Mission bags Fox Foundation grant for Parkinson’s program

Parkinson's brain cell
MJFF hopes Mission Therapeutics and the University of Oxford validate USP30 as a Parkinson's target.

Mission Therapeutics and the University of Oxford have landed a grant to fund testing of USP30 inhibitors. The Michael J. Fox Foundation for Parkinson’s Research (MJFF) is putting up the money to enable Mission to test its USP30 inhibitors in stem cell-derived Parkinson’s disease models.

MJFF is funding the research in an attempt to validate USP30 as a target for the treatment of Parkinson’s. By inhibiting USP30 in malfunctioning mitochondria, the scientists stand to show whether the therapeutic approach may improve the operation of the organelles and neuron health. And there is an expectation this will enable the identification of biomarkers of USP30 that will prove useful in subsequent clinical development.

Cambridge, U.K.-based Mission, like other research groups, was turned on to the potential to tackle neurodegenerative disorders by targeting USP30 through a paper published by Genentech scientists in 2014. That paper linked deubiquitylating enzyme (DUB) USP30 to mitophagy, the process through which mitochondria are degraded, and in doing so, suggested that inhibiting the enzyme could improve outcomes in Parkinson’s by promoting mitochondrial clearance.

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The discovery prompted Mission, a DUB specialist then focused on cancer, to branch out into neurodegenerative research. A program targeting USP30 is now one of two Mission is advancing toward the clinic, the other being a USP7-focused cancer project. Securing the grant gives Mission cash to supplement what is left of the £60 million ($75 million) it raised 14 months ago, plus the validation that comes from attracting the attention of MJFF.

“USP30 is one of the more promising DUBs associated with mitophagy, in terms of published data and feasibility of compound development,” Shalini Padmanabhan, Ph.D., MJFF’s associate director of research programs, said in a statement. “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.”

A team led by Oxford’s Richard Wade-Martins is contributing the disease models. Wade-Martins co-authored a journal paper describing the creation of induced pluripotent stem cell-derived dopaminergic models of Parkinson's disease in 2013. That project showed how the reprogramming of fibroblasts taken from patients with mutations linked to Parkinson’s could create tools to look at pathogenic mechanisms and hinted at the model’s applications in drug testing.