Mission Therapeutics recently announced the commencement of Phase I first-in-human clinical trial of MTX325 as a potential disease-modifying treatment for Parkinson’s Disease (PD). The potent selective central nervous system-penetrant compound is designed to improve mitochondrial quality and function by enhancing mitophagy. It targets a deubiquitylating enzyme, USP30 known to inhibit mitophagy. While normal cells can get rid of dysfunctional mitochondria through mitophagy, the clearance of dysfunctional mitochondria from cells is compromised in PD leading to reduced energy production, oxidative stress, inflammation, and potentially cell death.
Parkinson’s Disease (PD) is a movement disorder where dopaminergic neurons of the brain that control movement are preferentially lost, causing slowness in movement, rigidity of limbs and trunk, tremors, and postural instability. It affects over 10 million people worldwide, including almost one million in the US and around 1.2 million in Europe. These numbers are set to rise as populations age. Current treatments for PD can only reduce symptoms like tremors, slowness of movement, and cognitive problems, but none addresses the underlying neuronal death responsible for this devastating disease.
The safety, tolerability, pharmacokinetics, and brain penetration of MTX325 have already been evaluated among healthy volunteers. This year single ascending, multiple dose ascending, and elderly healthy volunteer cohorts will be included in the trial while recruitment of PD patients will start in 2025.
Apart from CNS targeting MTX325, Mission Therapeutics is also developing a peripheral version, MTX652. Through inhibition of USP30, these small drug molecules will promote the clearance of dysfunctional mitochondria thereby improving overall cellular health. Both MTX652 and MTX325 could potentially be used to treat any disease or condition driven by mitochondrial dysfunction like Kidney Disease, Heart Failure, idiopathic pulmonary fibrosis, Alzheimer’s disease, and Duchenne’s Muscular Dystrophy.
Dr. Rueben Das, Ph.D.
