Inhibiting an enzyme called USP30 in mice protects dopamine-producing neurons, which are typically lost as Parkinson's disease (PD) progresses. The corresponding study was published in Nature Communications.
PD is a neurodegenerative condition characterized by a progressive loss of dopaminergic neurons in the brain. Symptoms of PD include tremors, stiffness, and difficulty in balance and coordination. Around 10 million people have the condition worldwide.
Studies suggest that loss of dopaminergic neurons in PD may result from problems in clearing old and dysfunctional mitochondria- 'cellular powerhouses'- from cells. In the current study, researchers thus focused on an enzyme known as USP30 that plays a role in this process.
To begin, they observed a mouse model of PD that had been genetically modified to lack the gene that produces USP30. Ultimately, they found that mice without USP30 were protected against developing PD-like motor symptoms, had improved clearance of damaged mitochondria from neurons, and were protected against loss of dopaminergic neurons.
The researchers next tested a proprietary molecule known as MTX115325 developed by Mission Therapeutics that can block USP30's action in dopamine-producing neurons. They found that inhibiting USP30's action increased clearance of dysfunctional mitochondria and protected dopaminergic neurons in mouse models of PD as well as human cells.
"The two experimental strategies together are much more convincing than either alone," said senior author David K. Simon, MD, Ph.D., Director of the Parkinson's Disease & Movement Disorders Center at BIDMC, and a professor of neurology at Harvard Medical School, in a press release.
"Together, our very significant findings support the idea that reducing USP30 warrants further testing for its potentially disease-modifying effects in PD," he added.
The researchers now hope to launch a Phase 1 clinical trial to test Mission Therapeutic's molecule, also known as MTX325, in healthy volunteers and PD patients in early 2024.
Sources: Neuroscience News, Nature Communications, Parkinson's News Today
