June 16, 2024

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Inhibiting Key Enzyme Can Halt Parkinson’s Disease Progression

Breakthrough Discovery: Inhibiting Key Enzyme Can Halt Parkinson’s Disease Progression

Breakthrough Discovery: Inhibiting Key Enzyme Can Halt Parkinson’s Disease Progression

Researchers have achieved a significant breakthrough in Parkinson’s disease research. Their study reveals that inhibiting a specific enzyme, USP30, in mouse models can protect neurons that produce dopamine.

This discovery halts the progression of Parkinson’s disease, opening a gateway to new therapies for the approximately 10 million Parkinson’s patients worldwide.

Breakthrough Discovery: Inhibiting Key Enzyme Can Halt Parkinson's Disease Progression

A study published in “Nature Communications” by researchers at Beth Israel Deaconess Medical Center (BIDMC) sheds light on the cellular mechanisms driving the progression of Parkinson’s disease (PD).

Parkinson’s disease is a neurodegenerative disorder affecting around 10 million people globally. It results from the gradual loss of brain cells responsible for dopamine production, a crucial neurotransmitter essential for movement and coordination. As these neurons degenerate and dopamine levels decline, patients experience symptoms such as tremors, stiffness, and difficulties with balance and coordination.

Collaborating with colleagues from the University of Cambridge and Mission Therapeutics, researchers in the laboratory of Dr. David K. Simon, MD, Ph.D., Director of the Parkinson’s Disease and Movement Disorders Center at BIDMC, conducted complementary experiments. The results demonstrate that inhibiting a specific enzyme in mouse models can protect dopamine-producing neurons typically lost as Parkinson’s disease progresses, effectively preventing the advancement of the disease.

These findings pave the way for the development of novel therapies targeting this enzyme, which could slow down or prevent the progression of Parkinson’s disease within the human body—an unmet and critical need.

Dr. Tracy-Shi Zhang Fang, a lecturer in the Simon lab and the first author, stated, “Our lab focuses on unraveling the origins of Parkinson’s disease, aiming to one day slow or prevent the progression of the disease in patients. The current research results lay the groundwork for the future.”

Key Focus and Methods of the Research

Evidence suggests that the death of dopamine-producing cells in Parkinson’s patients occurs due to problems in clearing aging and dysfunctional mitochondria within cells—mitochondria being the cell’s energy source, sometimes referred to as the cell’s powerhouse.

The Simon lab and colleagues focused on an enzyme called USP30 playing a role in this process. They observed that the absence of USP30 prevented the onset of Parkinsonian motor symptoms, increased the clearance of damaged mitochondria in neurons, and prevented the loss of dopamine-producing neurons.

In a second set of experiments, the research team used a proprietary molecule developed by Mission Therapeutics to block the enzyme’s role in dopamine-secreting neurons, validating the findings from the gene knockout studies. Similar to gene knockout mice, inhibiting the enzyme’s function increased the clearance of dysfunctional mitochondria, safeguarding dopamine-secreting neurons.

Dr. Simon, a neurology professor at Harvard Medical School, stated, “Combining these two experimental approaches is more compelling than using either one alone. Our crucial findings collectively support the idea that reducing USP30 is worth further testing for its potential disease-modifying effects on Parkinson’s disease.”

Breakthrough Discovery: Inhibiting Key Enzyme Can Halt Parkinson’s Disease Progression

(source:internet, reference only)

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