Researchers have discovered a biochemical route that could lead to new Parkinson’s treatments.
The findings reveal how harmful protein build-up in brain cells causes the death of movement-controlling nerve cells, a hallmark of the condition.
The research was led by scientists at Case Western Reserve University.
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, said: “We’ve uncovered a harmful interaction between proteins that damages the brain’s cellular powerhouses, called mitochondria.
“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 team found that the toxic protein alpha-synuclein inappropriately interacts with an essential enzyme that supports cellular health, called ClpP.
Alpha-synuclein builds up abnormally in the brains of people with the condition.
Mitochondria, the cell’s energy producers, are harmed by this interaction, leading to neurodegeneration, the progressive loss of nerve cells, and brain cell death.
In several experimental models, the connection has also been shown to speed the disease’s progress.
The research team created CS2, a designed treatment that blocks the harmful protein interaction and restores healthy mitochondrial function.
CS2 works like a decoy, drawing alpha-synuclein to bind with it instead of damaging the cell’s energy factories.
CS2 also improved mobility and cognitive performance in a range of study models, including human brain tissue, patient-derived neurones and mouse models, by reducing brain inflammation.
Di Hu, research scientist in the School of Medicine’s Department of Physiology and Biophysics, said: “This represents a fundamentally new approach to treating Parkinson’s disease. Instead of just treating the symptoms, we’re targeting one of the root causes of the disease itself.”
Current treatments provide only short-term relief for symptoms.
In the next five years, the team hopes to move this discovery closer to possible clinical trials.
Optimising the medicine for human use, increasing safety and efficacy testing, identifying key molecular biomarkers and getting closer to clinical translation are the next steps.
Professor Qi said: “One day, 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.”
