About 1 million people in the United States are living with Parkinson’s disease, and nearly 90,000 new cases are diagnosed each year, according to the Parkinson’s Foundation. The condition is a long-term, progressive brain disorder that gradually destroys dopamine-producing nerve cells, which are critical for controlled, fluid movement.

Most available treatments focus on easing symptoms, but their benefits often fade over time. Now, researchers at Case Western Reserve University have identified a specific biological pathway that contributes to the underlying damage caused by the disease.

A Harmful Protein Chain Reaction

The study, recently published in Molecular Neurodegeneration, explains how the buildup of toxic proteins inside brain cells leads to the death of neurons responsible for movement, 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 investigation, the team discovered that alpha-synuclein, a protein known to accumulate in Parkinson’s disease, abnormally binds to an enzyme called ClpP. This enzyme normally helps maintain cellular health, but the interaction disrupts its function.

Damage to the Brain’s Energy Supply

When alpha-synuclein interferes with ClpP, mitochondria begin to fail. These structures act as the cell’s energy generators, and their impairment triggers widespread neurodegeneration and brain cell loss. Experiments across several research models also showed that this molecular interaction speeds up the progression of Parkinson’s disease.

To counter this process, the researchers developed a treatment known as CS2. The compound is designed to block the damaging protein interaction and help mitochondria recover their normal function. CS2 acts as a decoy, drawing alpha-synuclein away from ClpP and preventing it from harming the cell’s energy systems.

In multiple study models, including human brain tissue, patient-derived neurons and mice models, CS2 reduced brain inflammation and led to improvements in movement and cognitive performance.

Targeting the Disease, Not Just Symptoms

"This represents a fundamentally new approach to treating Parkinson’s disease," said Di Hu, a 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."

The breakthrough builds on Case Western Reserve’s strengths in mitochondrial biology and neurodegenerative disease research, along with its collaborative environment and advanced experimental models. These resources helped translate basic biological insights into a potential therapeutic strategy.

Next Steps Toward Clinical Use

Over the next five years, the team aims to move the discovery closer to human clinical trials. Planned efforts include refining the drug for use in people, expanding safety and effectiveness testing, identifying key molecular biomarkers tied to disease progression, and advancing toward patient-focused treatments.

"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."