(Press-News.org) CLEVELAND—About 1 million Americans suffer from Parkinson’s disease, with around 90,000 new cases diagnosed each year, according to the Parkinson’s Foundation. The chronic, degenerative brain disorder destroys dopamine-producing cells essential for smooth, coordinated movement.
Current treatments provide only short-term relief for such symptoms. But a team of Case Western Reserve University researchers have discovered a particular biochemical route that plays a role in the debilitating neurological condition.
Their findings, published recently in Molecular Neurodegeneration, reveal how harmful protein buildup in brain cells causes movement-controlling neurons to die—a hallmark of Parkinson’s disease.
“We’ve uncovered a harmful interaction between proteins that damages the brain’s cellular powerhouses, called mitochondria,” said Xin Qi, the study’s senior author and Jeanette M. and Joseph S. Silber Professor of Brain Sciences at the Case Western Reserve School of Medicine. “More importantly, we’ve developed a targeted approach that can block this interaction and restore healthy brain cell function.”
After three years of research, the scientists found that the toxic protein alpha-synuclein inappropriately interacts with an essential enzyme that supports cellular health in Parkinson’s disease, called ClpP.
The cell’s energy producers, the mitochondria, are harmed by this interaction, which results in neurodegeneration and brain cell death. In several experimental models, the connection has also been shown to accelerate the disease’s progress.
The research team created CS2, a specifically designed treatment that blocks the harmful protein interaction and reinstates healthy mitochondrial function. CS2 works like a decoy. It tricks alpha-synuclein into binding with it instead of damaging the cell’s energy factories. CS2 also improved mobility and cognitive performance in a variety of study models, including human brain tissue, patient-derived neurons and mice models, by reducing brain inflammation.
“This represents a fundamentally new approach to treating Parkinson’s disease,” said Di Hu, research scientist in the School of Medicine’s Department of Physiology and Biophysics. “Instead of just treating the symptoms, we’re targeting one of the root causes of the disease itself.”
Case Western Reserve’s long-standing interdisciplinary collaboration, expertise in mitochondrial biology and neurodegenerative disease, access to sophisticated and disease-relevant model systems and proven track record of converting basic discoveries into therapeutic approaches all contributed to the foundation for such a discovery.
In the next five years, the team hopes to move this discovery closer to possible clinical trials. Optimizing the medicine for human use, increasing safety and efficacy testing, finding important molecular biomarkers involved in the illness process and getting closer to clinical translation for patients are the next steps.
“One day,” Qi said, “we hope to develop mitochondria-targeted therapies that will enable people to regain normal function and quality of life, transforming Parkinson’s from a crippling, progressive condition into a manageable or resolved one.”
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About Case Western Reserve University
As one of the fastest-growing research universities in the United States, Case Western Reserve University is a force in career-defining education and life-changing research. Across our campus, more than 12,000 students from around the world converge to seek knowledge, find solutions and accelerate their impact. They learn from and collaborate with faculty members renowned for expertise in medicine, engineering, science, law, management, dental medicine, nursing, social work, and the arts. And with our location in Cleveland, Ohio—a hub of cultural, business and healthcare activity—our students gain unparalleled access to academic, research, clinical and entrepreneurial opportunities that prepare them to join our network of more than 125,000 alumni worldwide. Visit case.edu to see why Case Western Reserve University is built for those driven to be a force in the world.
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