A collaboration between scientists at Rutgers University and The Scripps Research Institute 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 over 10 million worldwide according to the Parkinson's Foundation, is a neurodegenerative disorder with no cure. Symptoms develop slowly over time and can be debilitating to patients, who most recognizably develop tremor, slow movements and a shuffling gait.
A key feature of Parkinson's disease is a protein named α-synuclein, which accumulates 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. Because higher levels of the protein in the brain speed the formation of its toxic forms, scientists have been looking for ways to decrease the protein production as a form of treatment.
In 2014, Parkinson's disease expert and scientist M. Maral Mouradian, MD, William Dow Lovett Professor of Neurology and director of the Rutgers Robert Wood Johnson Medical School Institute for Neurological Therapeutics, contacted Matthew D. Disney, PhD, chemistry professor at Scripps in Florida, to explore a novel idea for treating Parkinson's disease using a new technology developed by Dr. Disney.
Dr. Disney's method matches RNA structure, rather than proteins, with small molecules or drug-like compounds. The two collaborators believed this innovative technology 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. Since the protein itself is undruggable, RNA could be a more robust and reliable target.
They were right. The NIH-funded study, which was published in the Proceedings of the National Academy of Sciences on January 3rd, 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 Synucleozid, reduces specifically α-synuclein levels, thus, having the potential of preventing disease progression.
Says Dr. Mouradian:
Currently, there is no cure for Parkinson's disease and it is truly a devastating 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."
She explains that such a treatment would be most effective for people who are in the early stages of the disease with minimal symptoms.
"Several other experimental drugs 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."