In a recent publication, Northwestern Medicine scientists identified two drugs that stimulate stem cells in the central nervous system that have the potential to repair myelin, the protective coating around neurons that is damaged in the autoimmune disease multiple sclerosis (MS).
Part of a multi-institutional team, Stephen D. Miller, PhD, professor in Microbiology-Immunology, tested the drugs in different mouse models of MS; the results were published in Nature.
Previous research involved creating a special screen using progenitor cells, a type of stem cell in the central nervous system, to test existing drugs to determine if they activated the progenitor cells to form new myelinating cells called ogligodendrocytes.
In the current study, the scientists observed two drugs, miconazole, an antifungal, and clobetasol, a corticosteroid, that were effective in promoting myelination in cell cultures and mouse models.
Even though the myelin repair drugs worked, they had only a modest effect on improving disease progression over time. Miller believes they would work best in combination with an immune regulatory approach.
“If you try to use these drugs late in the disease, even if they are successful in making more myelin, the underlying autoimmune response isn’t addressed and continues to attack the myelin,” Miller said. “It’s like throwing more wood on the fire – you really have to take a two-pronged approach.”
Miller explained that immune regulation would prevent further damage, while myelin repair drugs like those tested in the current study could fix the current damage, with the hope to regain full function.
The collaboration with scientists at Case Western Reserve University School of Medicine will continue to identify other drugs in future screens and test these drugs in animal models of MS.
“I think this really starts a new era for our lab. The data that comes out of approaches such as this study, and the drugs that are identified will now be the prime candidates that we test in combination with our immunoregulatory strategies, and gives our research greater clinical relevance,” he said.
The research was supported by National Institutes of Health grants NS085246, NS030800 and NS026543, New York Stem Cell Foundation, Myelin Repair Foundation and National Institutes of Health pre-doctoral training grants T32GM008056 and F30CA183510.