Mission Therapeutics announces publication in Nature Reviews Drug Discovery of article highlighting how neurodegenerative diseases can be tackled by enhancing mitophagy

• Review article in high impact journal outlines the evidence that neurodegenerative diseases –including Parkinson's, Alzheimer's, ALS and Huntington's – can be addressed by boosting mitophagy, the quality control system cells use to remove dysfunctional mitochondria
• Strong evidence has emerged that deficient mitophagy is an underlying cause of neurodegenerative disease
• Momentum is building, with the first selective mitophagy enhancers aimed at modifying the course of neurodegenerative diseases entering clinical trials in the last 12 months

CAMBRIDGE, England, Jan. 15, 2025 /PRNewswire/ -- Mission Therapeutics ("Mission"), a clinical-stage biotech company developing first-in-class therapeutics targeting mitophagy, today announces the publication of a review article titled Targeting mitophagy in neurodegenerative diseases in the journal Nature Reviews Drug Discovery. The peer-reviewed article can be viewed here.

It outlines the progress scientists have made in identifying that mitochondrial dysfunction is a hallmark of neurodegenerative disease; how their understanding of the molecular pathways that underpin the mitophagy process has advanced; and the subsequent development of two molecular approaches – USP30 inhibition and PINK1 activation – which are now being tested in early-stage clinical trials.

Dr Paul Thompson, Chief Scientific Officer at Mission Therapeutics, said: "Fresh scientific approaches are needed if we as a society are to address the growing burden of neurodegenerative diseases, which are becoming ever more common as populations age. This timely review outlines the significant potential that enhancing mitophagy has in tackling a wide range of neurodegenerative diseases including Parkinson's, Alzheimer's, amyotrophic lateral sclerosis (ALS) and Huntington's."

Dr Laura Parton, Senior Director at Mission Therapeutics, said: "We now have a deep understanding of how the build-up of dysfunctional mitochondria can contribute to neurodegenerative diseases – and how we can go about addressing this problem with selective mitophagy enhancers, particularly those focussing on the USP30/PINK1/Parkin mitophagy pathway. After more than 30 years of research, the area is now coming to fruition, with three such drugs entering clinical trials in the last 12 months."

The review was written by a team of renowned mitophagy experts from across industry and academia, including Mission scientists Dr Paul Thompson and Dr Laura Parton; Professor Miratul Muqit and Odetta Antico of Dundee University; and Dr Nicholas T. Hertz, co-founder of Mitokinin LLC.

Mission Therapeutics is a global leader in discovering and developing innovative therapeutics that promote mitophagy, the quality control process cells use to remove dysfunctional mitochondria, thereby safeguarding their health and function. Effective mitophagy is particularly important for the ongoing health of neurons as, unlike most cells, they do not self-renew throughout an individual's lifetime.

About Mission Therapeutics

Mission Therapeutics is a world leader in discovering and developing novel therapeutics which promote the removal of dysfunctional mitochondria, promoting cell health and function. Mitochondria are energy producing organelles which require lifetime quality control through a ubiquitin-mediated clearance mechanism known as mitophagy. In certain situations, such as cellular stress, cell injury, and/or defects of the mitophagy process, the mitochondria can become dysfunctional and damaging to the cell, leading to reduced energy production, oxidative stress, inflammation and potentially cell death. Dysfunctional mitochondria are significant drivers of disease pathophysiology in acute kidney injury (AKI), Parkinson's disease (PD), heart failure, Duchenne's Muscular Dystrophy, IPF, mitochondrial diseases and Alzheimer's.

USP30 is a deubiquitylating enzyme that constantly removes ubiquitin from mitochondria, providing a potential brake on clearance of dysfunctional mitochondria. Mission is currently developing two small molecule drugs, MTX652 (peripheral) and MTX325 (targeting the CNS) which, through inhibition of the mitochondrial DUB enzyme USP30, will promote clearance of dysfunctional mitochondria – consequently improving overall cellular health. Mission's USP30 inhibitors MTX652 and MTX325 could potentially be used to treat any disease or condition driven by mitochondrial dysfunction.

Mission is backed by blue chip investors including Pfizer Venture Investments, Sofinnova Partners, Roche Venture Fund, SR One, IP Group and Rosetta Capital.