Mission Earns MJFF Grant to Develop Familial Parkinson’s Treatment

Margarida Maia, PhD avatar

by Margarida Maia, PhD |

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Mission Therapeutics has been awarded a Therapeutic Pipeline Program grant from the Michael J. Fox Foundation for Parkinson’s Research (MJFF) to advance development of its USP30 deubiquitylating enzyme (DUB) inhibitors for the treatment of familial Parkinson’s disease.

The grant, worth about $500,000, will be used to test these inhibitors in animals that model the disease, and to support preclinical selection of candidates for clinical trials.

“Receiving funding from the Michael J. Fox Foundation is a great accolade, recognizing the importance of USP30 as a potential therapeutic target for [Parkinson’s], and the quality of Mission’s chemistry,” Paul Thompson, PhD, chief scientific officer of Mission, said in a press release. “We hope this will be the first of many Mission DUB inhibitor programs that can address specific disease-driving pathologies in both Parkinson’s … and other neurodegenerative disorders.”

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USP30 is a DUB located in the mitochondria — the cells’ powerhouses —  whose dysfunction has been linked to Parkinson’s. USP30 negatively regulates mitophagy, a process in which damaged or excess mitochondria are tagged with ubiquitin and then cleared from the cells, by removing the ubiquitin tags put in place by a protein called Parkin.

However, in some forms of familial Parkinson’s, Parkin is mutated, leading to a toxic accumulation of mitochondria that ends up damaging nerve cells in the brain. This results in symptoms of early-onset Parkinson’s.

It is thought that inhibiting USP30 has the potential to increase clearance of mitochondria, resulting in healthier nerve cells. Importantly, Mission’s USP30 inhibitors can enter the central nervous system (CNS, the brain and spinal cord).

The new grant will fund studies to see how well CNS-penetrant USP30 inhibitors can protect neurons (nerve cells) that produce dopamine — the neurotransmitter that is missing in the brains of people with Parkinson’s.

The researchers also will look at indicators of mitochondrial damage, such as markers of inflammation and mutations in the DNA located in mitochondria, which often are evident in people with early-onset Parkinson’s.

“The number of people living with Parkinson’s continues to grow, but there are currently no treatments capable of stopping or reversing progression of this debilitating disease,” said Shalini Padmanabhan, PhD, director of research programs at MJFF. “Mission’s CNS-penetrant USP30 DUB inhibitors may offer an opportunity to make a meaningful impact on the lives of [Parkinson’s] patients by improving the health of cells in the brain. We are proud to support a project aiming to meet this critical unmet need.”

In the future, USP30 inhibitors may have an application in idiopathic Parkinson’s and other diseases.


For now, Mission plans to have its first USP30 inhibitor — one that is unable to enter the CNS — enter a clinical trial for kidney and liver disease in early 2022.