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."
About the Mount Sinai Health System
The Mount Sinai Health System is an integrated health system committed to providing distinguished care, conducting transformative research, and advancing biomedical education. Structured around seven hospital campuses and a single medical school, the Health System has an extensive ambulatory network and a range of inpatient and outpatient services—from community-based facilities to tertiary and quaternary care.
The System includes approximately 7,100 primary and specialty care physicians; 12 joint-venture ambulatory surgery centers; more than 140 ambulatory practices throughout the five boroughs of New York City, Westchester, Long Island, and Florida; and 31 affiliated community health centers. Physicians are affiliated with the renowned Icahn School of Medicine at Mount Sinai, which is ranked among the highest in the nation in National Institutes of Health funding per investigator. The Mount Sinai Hospital is in the "Honor Roll" of best hospitals in America, ranked No. 15 nationally in the 2016-2017 "Best Hospitals" issue of U.S. News & World Report. The Mount Sinai Hospital is also ranked as one of the nation's top 20 hospitals in Geriatrics, Gastroenterology/GI Surgery, Cardiology/Heart Surgery, Diabetes/Endocrinology, Nephrology, Neurology/Neurosurgery, and Ear, Nose & Throat, and is in the top 50 in four other specialties. New York Eye and Ear Infirmary of Mount Sinai is ranked No. 10 nationally for Ophthalmology, while Mount Sinai Beth Israel, Mount Sinai St. Luke's, and Mount Sinai West are ranked regionally. Mount Sinai's Kravis Children's Hospital is ranked in seven out of ten pediatric specialties by U.S. News & World Report in "Best Children's Hospitals."