Mount Sinai Researchers Identify Molecular Changes in the Brain that May Increase Risk for Multiple Sclerosis
First genome-wide study in brain tissue from MS patients.
Researchers have long suspected that a combination of genetic and environmental factors conspire in the development of multiple sclerosis (MS), an inflammatory disease of the central nervous system that strips nerve cells of their protective myelin sheath. A new study, published today in the online issue of Nature Neuroscience, highlights some of the molecular pathways critical to the onset and progression of this disease.
The study, led by genomics experts at the Icahn School of Medicine at Mount Sinai, was the first to identify so-called epigenetic changes – modifications to our DNA caused by environmental factors such as diet or exposure to chemicals – across the entire genome. Epigenetic changes have been shown to influence the expression and function of genes.
"Previous studies have linked environmental factors, such as vitamin D levels and oxidative stress, to MS," said lead investigator Patrizia Casaccia, MD, PhD, Professor of Neuroscience, Department of Genetics and Genomics at the Icahn School of Medicine at Mount Sinai. "But earlier research was limited in terms of scope and focus. By looking for epigenetic changes across the entire genome, we were able to identify molecular pathways that are involved in the disease process."
The investigators used a sophisticated microarray to analyze levels of DNA methylation, an epigenetic modification that regulates gene function, in post-mortem, disease-free brain tissue from patients who had MS and from people who did not have the disease. The analysis, led by Andrew Sharp, PhD, MD, Assistant Professor in the Department of Genetics and Genomics at the Icahn School of Medicine, revealed that tissue from MS patients had undergone a variety of subtle epigenetic changes that inhibit the formation of myelin and increase inflammation.
"Although subtle, these changes are significant in terms of their ability to increase a patient's risk for MS," said Dr. Sharp. "Looking at healthy brain tissue was critical to ensuring that the changes we observed were not due to the disease process itself."
"This study clearly demonstrates that the brains of MS patients harbor molecular changes, likely caused by environmental factors, that increase their susceptibility to the disease," said Dr. Casaccia. "Our findings constitute a disease signature that MS researchers can target to develop more effective medications for people with this neurological disease."
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The Mount Sinai Health System is New York City's largest academic medical system, encompassing eight hospitals, a leading medical school, and a vast network of ambulatory practices throughout the greater New York region. Mount Sinai is a national and international source of unrivaled education, translational research and discovery, and collaborative clinical leadership ensuring that we deliver the highest quality care—from prevention to treatment of the most serious and complex human diseases. The Health System includes more than 7,200 physicians and features a robust and continually expanding network of multispecialty services, including more than 400 ambulatory practice locations throughout the five boroughs of New York City, Westchester, and Long Island. The Mount Sinai Hospital is ranked No. 14 on U.S. News & World Report's "Honor Roll" of the Top 20 Best Hospitals in the country and the Icahn School of Medicine as one of the Top 20 Best Medical Schools in country. Mount Sinai Health System hospitals are consistently ranked regionally by specialty and our physicians in the top 1% of all physicians nationally by U.S. News & World Report.