Research Reveals New Potential TherapyParkinson’s disease, which affects an estimated 10 million people worldwide and is the second-most common neurodegenerative disease, remains without a cure. But scientists like those at Northwestern Medicine are constantly researching the intricacies of the condition in hopes of developing therapies that can not only address the symptoms, but also offer disease-altering treatment. Most recently, that included establishing a better understanding of a protein that could reveal a pathway to direct therapy.
One of the hallmarks of Parkinson’s disease is the buildup of a protein called α-synuclein in the brain. The Northwestern Medicine scientists showed that too much α-synuclein impairs lysosomes, which remove debris in cells, by disrupting the hydrolase enzymes that digest the debris. Trafficking the lysosome enzyme into the lysosome is tightly regulated and α-synuclein impairs this process.
The team, led by Dimitri Krainic, MD, PhD, Aaron Montgomery Ward Professor and chair of Neurology at Northwestern University Feinberg School of Medicine, discovered this by reprogramming skin cells from patients with Parkinson’s disease into neurons. The team monitored the lysosomal system while cells aged over hundreds of days. They then demonstrated multiple strategies that could restore the hydrolase enzyme trafficking, thereby improving lysosome function.
The outcome of the study reveals a pathway for potential future therapies to treat Parkinson’s disease and its related disorders. Moreover, the trafficking defect is an early event for Parkinson’s patients. A treatment that reverses it, as demonstrated in the study, may be able to prevent degeneration. And the Northwestern Medicine team is already focused on developing small molecules for just that purpose.