Page 25 - RU Robert Wood Johnson Medicine • Summer 2020

M. Maral Mouradian, MD
Study Finds a Drug-Like Compound That
May Prevent Parkinson’s Disease Progression
ByJillianPrior | PortraitBySteveHockstein
Acollaboration between scientists at Rutgers Robert Wood Johnson Medical School and the Scripps Research Institute has led to the discovery of a small molecule that may slow down or stop the progression of Parkinson’s disease.
Parkinson’s, which affects 1 million people in the United States and more than 10 million worldwide, is a neurodegener- ative disorder with no cure. Symptoms develop slowly over time and can be debilitating to patients, who most recog- nizably develop tremors, slow movements, and a shuffling gait.
A key feature of Parkinson’s disease is a protein named α-synuclein, which accu- mulates in an abnormal form in brain cells, causing them to degenerate and die. However, it has been difficult to target α- synuclein because it does not have a fixed structure and keeps changing its shape, making it very difficult for drugs to target.
In 2014, Parkinson’s disease expert and scientist M. Maral Mouradian, MD, William Dow Lovett Professor of Neurology and director, Rutgers Robert Wood Johnson Medical School Institute for Neurological Therapeutics, contacted Matthew D. Disney, PhD, professor of chemistry at the Scripps campus in Jupiter, Florida, to explore a novel idea for treating Parkin- son’s using a new technology developed by Dr. Disney.
Dr. Disney’s method
matches RNA struc-
ture, rather than
proteins, with small
molecules or drug-like
compounds. The two
collaborators believed
this innovative tech-
nology could be used to find a drug that targets the messenger RNA that codes for α-synuclein in order to reduce production of the protein in the brains of Parkinson’s patients.
They were right. The study, funded by the National Institutes of Health and pub- lished in the Proceedings of the National Academy of Sciences on January 3, showed that by targeting messenger RNA, the team found a compound that prevents the harmful Parkinson’s protein from being made. This new compound, named Synu- cleozid, specifically reduces α-synuclein levels and toxicity, thus having the poten- tial to prevent disease progression.
“Currently, there is no cure for Park- inson’s disease. 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 Dr. Mouradian.
“We found the molecule to be very selective at both the RNA and the protein level,” says Dr. Disney.
Dr. Mouradian explains that most approaches being tested for Parkinson’s target a very late stage in α-synuclein– mediated neurodegeneration, whereas Synucleozid targets the process before it is initiated. This maximizes the potential to slow down or stop disease progression. Dr. Mouradian feels this discovery is “highly promising” and is eager for the next steps in optimizing and testing the compound, with the hope of starting human clinical trials in a few years. M
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