Penn Medicine researchers have discovered that hypermethylation - the epigenetic ability to turn down or turn off a bad gene implicated in 10 to 30 percent of patients with Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Degeneration (FTD) - serves as a protective barrier inhibiting the development of these diseases. Their work, published online on March 20, 2015 in Neurology, may suggest a neuroprotective target for drug discovery efforts. "This is the first epigenetic modification of a gene that seems to be protective against neuronal disease," says lead author Corey McMillan, Ph.D., Research Assistant Professor of Neurology in the Frontotemporal Degeneration Center in the Perelman School of Medicine at the University of Pennsylvania. Expansions in the offending gene, C9orf72 (chromosome 9, open reading frame 72), have been linked with TAR DNA binding protein (TDP-43) which is the pathological source that causes ALS and FTD. "Understanding the role of C9orf72 has the possibility to be truly translational and improve the lives of patients suffering from these devastating diseases," says senior author, Edward Lee, M.D., Ph.D., Assistant Professor of Neuropathology in Pathology and Laboratory Medicine at Penn. Dr. McMillan and team evaluated 20 patients recruited from both the FTD Center and the ALS Center at the University of Pennsylvania who screened positive for a mutation in the C9orf72 gene and were clinically diagnosed with FTD or ALS. All patients completed a neuroimaging study, a blood test to evaluate C9orf72 methylation levels, and a brief neuropsychological screening assessment. The study also included 25 heathy controls with no history of neurological or psychiatric disease.
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