Researchers discover new drugs of MS

Researchers discover new drugs of MS

Researchers discover new drugs to combat the root cause of multiple sclerosis

New research published this week in Nature has found several drugs could lead to new treatment options for multiple sclerosis (MS), including two drugs that effectively treat MS at the source, in vivo. When administered at the peak of disease, these two drugs showed a striking reversal of disease severity.

At the pathological level, MS is a disease in which the immune system attacks the protective myelin sheath, a type of insulation that covers nerves, ultimately disrupting communication between the brain and the body and leading to nerve deterioration. To prevent neural degeneration requires remyelination through new oligodendrocytes, which create the myelin sheath. These two drugs, miconazole and clobetasol, were found to treat the source of the problem by reversing this process, increasing the number of new oligodendrocytes and enhancing remyelination.

“Current therapies focus on stopping immune system attacks, slowing the progression of the disease. Our research is focused on trying to repair the brain itself, to stop the disease rather than slow it,” said Robert Miller, Ph.D., co-author of the study and senior associate dean for research, Vivian Gill Distinguished Research Professor, and professor of anatomy and regenerative biology at the George Washington University School of Medicine and Health Sciences. “While successful in vivo, we’re looking forward to continuing our research through further testing of miconazole and clobetasol, taking the next steps to finding treatments for MS.”

Performed at Case Western Reserve University, researchers discovered the therapeutic compounds for enhancing myelination from oligodendrocyte progenitor cells through screening a library of bioactive small molecules. Oligodendrocyte progenitor cells are stem cells found in the central nervous system and the principal source of myelinating oligodendrocytes.

Finding this cellular target for pharmacological intervention, Miller and co-author Paul Tesar, Ph.D., the Dr. Donald and Ruth Weber Goodman Professor of Innovative Therapeutics, and associate professor in the Department of Genetics & Genome Sciences at the Case Western Reserve School of Medicine, found seven drugs that enhance generation of mature oligodendrocytes and found that miconazole and clobetasol could promote myelination. Miconazole was found to function directly as a remyelinating drug with no effect on the immune system, whereas clobetasol was found to be a potent immunosuppressant, as well as a remyelinating agent.

“To replace damaged cells, much of the stem cell field has focused on direct transplantation of stem cell-derived tissues for regenerative medicine, and that approach is likely to provide enormous benefit down the road,” said Tesar, also a New York Stem Cell Foundation Robertson Investigator and member of the National Center for Regenerative Medicine. “But here we asked if we could find a faster and less invasive approach by using drugs to activate native stem cells already in the adult nervous system and direct them to form new myelin. Our ultimate goal was to enhance the body’s ability to repair itself.”

“Drug-based modulation of endogenous stem cells promotes functional remyelination in vivo,” was published in Nature on April 20.

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The above post is reprinted from materials provided by George Washington University. Note: Materials may be edited for content and length.

Journal Reference:

1. Fadi J. Najm, Mayur Madhavan, Anita Zaremba, Elizabeth Shick, Robert T. Karl, Daniel C. Factor, Tyler E. Miller, Zachary S. Nevin, Christopher Kantor, Alex Sargent, Kevin L. Quick, Daniela M. Schlatzer, Hong Tang, Ruben Papoian, Kyle R. Brimacombe, Min Shen, Matthew B. Boxer, Ajit Jadhav, Andrew P. Robinson, Joseph R. Podojil, Stephen D. Miller, Robert H. Miller, Paul J. Tesar. Drug-based modulation of endogenous stem cells promotes functional remyelination in vivo.Nature, 2015; DOI: ۱۰۳۸/nature14335