Instead of attacking the elusive protein causing Parkinson’s, the RNA being formed is targeted by a new compound.
Parkinson’s disease is a neurodegenerative disorder characterized by tremor, slowness of motion, stiffness of the limbs, and problems with walking and balance.
A misfolded protein called α-synuclein in Parkinson’s causes brain cells to degenerate and kill. The more α-synuclein accumulates, the more neurons die.
Now researchers at Rutgers University in New Brunswick, NJ, and Scripps Research in Jupiter, Florida, have developed a way to reduce the amount of α-synuclein that the body produces.
New technology helped scientists to identify a compound that would shut down messenger RNA (mRNA) coding for the destructive protein, preventing α-synuclein development and Parkinson’s progression.
The study funded by the NIH researchers appears in National Academy of Sciences Proceedings.
The need for an innovative solution
More than 10 million people worldwide are diagnosed with Parkinson’s disease, with 1 million of them in the United States, according to the Parkinson’s Foundation.
About 60,000 US adults are diagnosed with the disease each year.
Parkinson’s incidence increases with age, though about 4 percent of people diagnosed are under 50 years old. The males are 1.5 times more likely than women to develop Parkinson’s.
“There is no cure for Parkinson’s disease at present and it is really a debilitating disease,” says professor of neurology M. Rutgers Maral Mouradian Robert Wood Johnson Medical School Center for Neurological Therapeutics, and a study co-author.
Numerous other methods have tried to address the development and accumulation of α-synuclein, but since the protein does not have a normal structure and constantly changes its form, it has proved difficult to strike with drugs.
“Several other experimental drugs,” says Mouradian, “currently being developed for Parkinson’s disease are antibodies targeting a very late stage of α-synuclein protein aggregates.”
“We want to prevent these protein clumps from forming first, until they cause damage and contribute to disease progression.”
The new research began when Mouradian reached out to chemistry professor Matthew D. Disney of Scripps to investigate the potential for a new technology that Disney had developed to bind small-molecules or drug-like compounds to RNA structures.
The scientists had a hunch to find a match for the mRNA that coded for α-synuclein, and that the mRNA may give a more stable, reliable target than α-synuclein itself. The hunch did pay off.
“We first discovered a drug-like compound that has the potential to slow down the disease before it progresses through a completely new approach,” Mouradian says.
They have called their compound synucleozide, and Mouradian describes it as “highly promising.”
While synucleozide may be most beneficial in people with minimal symptoms and at 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.”
Synucleozide may be of concern beyond Parkinson’s as α-synuclein has dementia symptoms with Lewy bodies, another progressive disease affecting one million people in the United States alone.
The analysis also sheds light on Disney’s promise of RNA / protein matching technology. As Mouradian notes, “Our study’s scope could go beyond people with Parkinson’s disease into many other neurodegenerative diseases.”
“It’s a classic example of how interdisciplinary work contributes to significant change.”