Researchers at the Icahn School of Medicine at Mount Sinai have identified new compounds that could protect from multiple sclerosis related damage, based on studies in mice with nervous system damage, mimicking MS. The study appeared in the journal Nature Neuroscience.
MS is an autoimmune attack on the body’s own myelin — a fatty substance that wraps around nerve cells and allows them to conduct impulses. When myelin is damaged, symptoms such as problems with movement, pain, poor balance, vision loss and lost sensation can result. MS is unpredictable and life-debilitating and new treatments are greatly needed.
Jeffery Haines, PhD, a post-doctoral fellow at Mount Sinai and the study’s lead author commented, “The compounds identified in this study, when administered orally, both reduced the inflammation that is a hallmark of multiple sclerosis and protected against the nerve cell damage seen in mouse models of the disease. The multiple sclerosis drugs currently on the market and being tested elsewhere seek to reduce the immune attack on cells, but none target neurodegeneration nor do they work to restore nerve cell function. The findings of this new study represent an exciting step in the process of advancing new oral treatment options.”
A molecule called XPO1 (also called CRM1,) may be involved in multiple sclerosis as well as other diseases. The researchers decided to target this molecule.
They tested whether drugs designed to block XPO1/CRM1 could stop MS in mouse models. Two drugs were identified, KPT-276 and KPT-350, that acted on XPO1/CRM1. The medications seemed to protect cells from what is called free-radical damage — the production of damaging ions faster than the body can remove them. Free radical damage may be one way that the nervous system is affected in MS. Not only did the medications block free radical damage, they also prevented inflammation by stopping cells involved in inflammation from dividing. Immune cells can cause inflammation, which may be positive in infection, but is damaging in MS in which the immune cells attack the body’s own myelin. Stopping immune cells in the case of MS is therefore positive.
The medications helped the mice, which lost movement due to an experimental treatment that damaged myelin, to regain some movement as well.
Patrizia Casaccia, MD, PhD, Professor of Neuroscience, Genetics and Genomic Sciences at Mount Sinai and senior author of the study noted, “The study results elucidate the molecular mechanisms underlying disease progression in multiple sclerosis models, providing a basis for future clinical trials to determine safety and efficacy of these chemical agents in humans with demyelinating disorders.”