Instead of targeting the tricky protein behind Parkinson’s, a new compound attacks the RNA that produces it.
Parkinson’s disease is a neurodegenerative disorder characterized by tremor, slowness of movement, limb rigidity, and walking and balance issues.
In Parkinson’s, a misfolded protein named α-synuclein causes the degeneration and destruction of brain cells. The more α-synuclein builds up, the more neurons die.
Now, scientists from Rutgers University in New Brunswick, NJ, and Scripps Research in Jupiter, Florida, have developed a way to decrease the amount of α-synuclein the body produces.
New technology allowed scientists to identify a compound that shuts down the messenger RNA (mRNA) coding for the destructive protein, preventing the production of α-synuclein and the progression of Parkinson’s.
The researchers’ NIH-funded study appears in the Proceedings of the National Academy of Sciences.
According to the Parkinson’s Foundation, over 10 million people worldwide are living with Parkinson’s disease, with 1 million of those being in the United States.
Each year, about 60,000 U.S. adults receive a diagnosis of the disease.
The incidence of Parkinson’s increases with age, although about 4% of people who receive a diagnosis are less than 50 years old. Men are 1.5 times more likely to develop Parkinson’s than women.
“Currently, there is no cure for Parkinson’s disease, and it is truly a devastating disease,” says neurology professor M. Maral Mouradian of Rutgers Robert Wood Johnson Medical School Institute for Neurological Therapeutics, and a co-author of the study.
Numerous other approaches have attempted to address the production and buildup of α-synuclein, but since the protein has no regular structure and continually changes shape, it has proven difficult to hit with medication.
“Several other experimental drugs,” says Mouradian, “currently being tested for Parkinson’s disease are antibodies that target a very late stage of α-synuclein protein aggregates.”
“We want to prevent these protein clumps from forming in the first place before they do damage and lead to advancing disease.”
The new research began when Mouradian reached out to chemistry professor Matthew D. Disney of Scripps to explore the potential for a new technology that Disney had invented for matching RNA structures with small-molecules or drug-like compounds.
The scientists had a hunch that they might find a match for the mRNA that coded for α-synuclein and that the mRNA might offer a more stable, predictable target than α-synuclein itself. The hunch paid off.
“For the first time, we discovered a drug-like compound that has the potential to slow down the disease before it advances through an entirely new approach,” says Mouradian.
They named their compound Synucleozid, and Mouradian describes it as “highly promising.”
While Synucleozid may be most effective in people with minimal symptoms and who are in the early stages of Parkinson’s, Mouradian says, “This new compound has the potential to […] change the course of life for people with this devastating disease.”
Synucleozid may be of value beyond Parkinson’s since α-synuclein has implications in dementia with Lewy Bodies, another progressive condition that affects 1 million people in the U.S. alone.
The study also makes clear the promise of Disney’s RNA/protein-matching technology. As Mouradian says, “The reach of our study could go beyond people with Parkinson’s disease to many other neurodegenerative diseases.”
“It is a classic example of how interdisciplinary research leads to significant change.”