Mission Therapeutics announces publication in Nature Communications outlining potential of experimental drug MTX325 as a disease-modifying therapy for Parkinson’s Disease

International research collaboration between Harvard Medical School, Cambridge University and Mission Therapeutics

CAMBRIDGE, UK, 13 November, 2023 – Mission Therapeutics (“Mission”), a clinical-stage biotech company developing first-in-class therapeutics targeting mitophagy, today announces the publication of a peer-reviewed article titledKnockout or inhibition of USP30 protects dopaminergic neurons in a Parkinson’s Disease (PD) mouse model’ in the journal Nature Communications, which can be freely accessed here. The research was the result of collaborative work between Cambridge University, Harvard Medical School, and Mission Therapeutics.

Mission Therapeutics is a global leader in discovering and developing innovative therapeutics that promote mitophagy. This quality control process enables the removal of dysfunctional mitochondria, thereby improving cell health and function. Parkinson’s Disease is highly associated with mitochondrial dysfunction, making it a key pathophysiological driver. Mission believes that by improving mitophagy, it can reduce the burden of dysfunctional mitochondria and thus slow or prevent the progression of Parkinson’s Disease, which is a major unmet need for patients with this condition.

Dr Paul Thompson, Chief Scientific Officer at Mission Therapeutics, said: “It is well recognized that mitochondrial dysfunction is a key driver of Parkinson’s Disease mechanisms, in particular, playing an important role in the degeneration of brain cells that produce dopamine. By inhibiting the enzyme USP30, Mission’s experimental drug MTX325 helps promote mitochondrial quality control by increasing the removal of dysfunctional mitochondria. This is likely to have a positive impact on dopaminergic neurons undergoing chronic degenerative processes, which result in functional impairment. This paper strongly supports further study of USP30 inhibition as a potential disease-modifying therapy for Parkinson’s Disease.”

Dr Anker Lundemose, Chief Executive Officer at Mission Therapeutics, said: “The exciting findings of this Nature Communications paper are a tremendous boost to Mission’s Parkinson’s Disease programme. We look forward to starting our first in-human trial of MTX325 early next year.”

The Nature Communications paper outlines how Mission’s drug MTX325 has potential as a novel, disease-modifying treatment for Parkinson’s, by enhancing mitophagy and clearing dysfunctional mitochondria. Dysfunctional mitochondria are usually tagged for removal via mitophagy with a protein ‘flag’ called ubiquitin. However, the enzyme USP30 removes these flags, inhibiting normal mitophagy, leading to a build-up of dysfunctional mitochondria in cells. By inhibiting USP30, MTX325 helps restore normal mitophagy and thus cellular health.

The Nature Comms paper provides key experimental evidence to support USP30 as a valid target in PD through both in vitro mechanisms as well as in vivo PD models. Using both a USP30 knockout mouse model and a pharmacological strategy with Mission’s experimental USP30 inhibitor drug MTX325, we found that USP30 inhibition led to protection against loss of dopamine and dopaminergic neurons induced by alpha-synuclein in vivo and reduced potential biomarkers of disease including phosphorylated alpha-synuclein and glial cell activation.

These new findings suggest that maintaining healthy mitochondrial function by blocking USP30 may slow or even stop the progression of pathology which drives PD.

Prof Gabriel Balmus, Cambridge University, said: “Our study has shown that it is possible to enhance the removal of damaged mitochondria through a process called mitophagy. We demonstrated this by inhibiting the activity of USP30 in both mice and human cells, which resulted in the increased removal of damaged mitochondria and the subsequent protection of dopaminergic neurons against the harmful effects of Parkinson’s Disease, which would typically result in the neurons’ death. This research provides compelling evidence that USP30 is a promising therapeutic target for Parkinson’s disease, where there is a pressing need for disease-modifying treatments.”

Prof David K. Simon, Harvard Medical School, said: “Our study of USP30 KO mice in a synuclein-driven PD model clearly shows an advantage of removing USP30 for dopaminergic neuron protection and maintenance of normal motor function. It has been our pleasure to collaborate with Cambridge and Mission Therapeutics on these studies, and we are keen to see the outcomes of early MTX325 clinical investigations.”

Mission is planning to initiate a MTX325 Phase I trial in humans in early 2024.


For further information, please contact:

Mission Therapeutics Ltd:

Anker Lundemose MD PhD

Chief Executive Officer

Tel: +44 (0)1223 607 340

Optimum Strategic Communications:

Mary Clark, Stephen Adams, Vici Rabbetts

Email: mission@optimumcomms.com

Tel: +44 (0) 208 078 4357

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 has completed its first Phase I clinical study with MTX652, demonstrating a highly encouraging safety, tolerability and pharmacokinetic profile. A Phase II trial of MTX652 in patients at risk of acute kidney injury following cardiac surgery is planned to start in Q1 2024.

A Phase I trial of MTX325 in healthy volunteers and patients with PD is planned to start in Q1 2024. Mission is backed by blue-chip investors including Pfizer Venture Investments, Sofinnova Partners, Roche Venture Fund, SR One, IP Group and Rosetta Capital.