Scientists at the National Institutes of Health have singled out a molecule that could be useful to treat both a rare disorder--Gaucher disease--as well as the more common Parkinson’s disease. Neurons in patients with the disorders have an elevated level of alpha-synuclein; the researchers selected this molecule, NCGC607, to lower the levels of that protein, which could prove a treatment strategy.
“This research constitutes a major advance,” said Dr. Daniel Kastner, scientific director of NIH’s National Human Genome Research Institute (NHGRI) and director of the institute’s Division of Intramural Research, in a statement. “It demonstrates how insights from a rare disorder such as Gaucher disease can have direct relevance to the treatment of common disorders like Parkinson’s disease.”
Gaucher disease involves a mutation of GBA1, the gene that codes for the protein glucocerebrosidase. That protein normally works to dispose of certain lipids that are a cell waste product. A Gaucher patient inherits two mutated copies of GBA1; people with one mutated copy of GBA1 are more likely to develop Parkinson’s.
To elucidate the relationship between the two disorders, NIH researchers created pluripotent stem cells in the lab from skin cells of Gaucher patients with and without Parkinson’s disease. They were then converted into neurons with features identical to those in Gaucher patients. Then the scientists used high-throughput screening to find this molecule, which reverses the lipid accumulation and lowers the amount of alpha-synuclein.
Up next, researchers will test the new molecule to see if it could be developed into a drug candidate for both Gaucher and Parkinson’s patients.
“Until now, drugs used to treat Gaucher disease have not been able to enter the brain and reach those neurons that are affected in the most severe forms of Gaucher disease or in Parkinson’s disease,” said Dr. Ellen Sidransky, a senior investigator with NHGRI.
She has been researching Gaucher disease for almost 30 years and originally made the connection between Gaucher and Parkinson’s disease in 2001, the NIH noted.
The research was published in a recent issue of the Journal of Neuroscience. Sidransky collaborated with scientists from the National Institute of Neurological Disorders and Stroke and the National Center for Advancing Translational Sciences.
- here is the NIH release
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