"Two drugs already on the market  an antifungal and a steroid  may potentially take on new roles as treatments for multiple sclerosis. According to a study published in Nature today researchers discovered that these drugs may activate stem cells in the brain to stimulate myelin producing cells and repair white matter which is damaged in multiple sclerosis. The study was partially funded by the National Institute of Neurological Disorders and Stroke NINDS part of the National Institutes of Health. Specialized cells called oligodendrocytes lay down multiple layers of a fatty white substance known as myelin around axons the long wires that connect brain cells. Myelin acts as an insulator and enables fast communication between brain cells. In multiple sclerosis there is breakdown of myelin and this deterioration leads to muscle weakness numbness and problems with vision coordination and balance. To replace damaged cells the scientific field has focused on direct transplantation of stem cellderived tissues for regenerative medicine and that approach is likely to provide enormous benefit down the road. We asked if we could find a faster and less invasive approach by using drugs to activate native nervous system stem cells and direct them to form new myelin. Our ultimate goal was to enhance the bodys ability to repair itself said Paul J. Tesar Ph.D. associate professor at Case Western Reserve School of Medicine in Cleveland and senior author of the study. It is unknown how myelinproducing cells are damaged but research suggests they may be targeted by malfunctioning immune cells and that multiple sclerosis may start as an autoimmune disorder. Current therapies for multiple sclerosis include antiinflammatory drugs which help prevent the episodic relapses common in multiple sclerosis but are less effective at preventing longterm disability. Scientists believe that therapies that promote myelin repair might improve neurologic disability in people with multiple sclerosis. Adult brains contain oligodendrocyte progenitor cells OPCs which are stem cells that generate myelinproducing cells. OPCs are found to multiply in the brains of multiple sclerosis patients as if to respond to myelin damage but for unknown reasons they are not effective in restoring white matter. In the current study Dr. Tesar wanted to see if drugs already approved for other uses were able to stimulate OPCs to increase myelination. OPCs have been difficult to isolate and study but Dr. Tesar and his colleagues in collaboration with Robert Miller Ph.D. professor at George Washington University School of Medicine and Health Sciences in Washington D.C. developed a novel method to investigate these cells in a petri dish. Using this technique they were able to quickly test the effects of hundreds of drugs on the stem cells. The compounds screened in this study were obtained from a drug library maintained by NIHs National Center for Advancing Translational Sciences NCATS. All are approved for use in humans. NCATS and Dr. Tesar have an ongoing collaboration and plan to expand the library of drugs screened against OPCs in the near future to identify other promising compounds. Dr. Tesars team found that two compounds in particular miconazole an antifungal and clobetasol a steroid stimulated mouse and human OPCs into generating myelinproducing cells. Next they examined whether the drugs when injected into a mouse model of multiple sclerosis could improve remyelination. They found that both drugs were effective in activating OPCs to enhance myelination and reverse paralysis. As a result almost all of the animals regained the use of their hind limbs. They also found that the drugs acted through two very different molecular mechanisms. The ability to activate white matter cells in the brain as shown in this study opens up an exciting new avenue of therapy development for myelin disorders such as multiple sclerosis said Ursula Utz Ph.D. program director at the NINDS. Dr. Tesar and his colleagues caution that more research is needed before miconazole and clobetasol can be tested in multiple sclerosis clinical trials. They are currently approved for use as creams or powders on the surfaces of the body but their safety administered in other forms such as injections in humans is unknown. Offlabel use of the current forms of these drugs is more likely to increase other health concerns than alleviate multiple sclerosis symptoms. We are working tirelessly to ready a safe and effective drug for clinical use Dr. Tesar said. This work was supported by the NINDS NS NS NS the New York Stem Cell Foundation and the Myelin Repair Foundation New York City. The NINDS http is the nations leading funder of research on the brain and nervous system. The mission of NINDS is to seek fundamental knowledge about the brain and nervous system and to use that knowledge to reduce the burden of neurological disease. The National Center for Advancing Translational Sciences is a distinctly different entity in the research ecosystem. Rather than targeting a particular disease or fundamental science NCATS focuses on what is common across diseases and the translational process. The Center emphasizes innovation and deliverables relying on the power of data and new technologies to develop demonstrate and disseminate advancements in translational science that bring about tangible improvements in human health. For more information visit http About the National Institutes of Health NIH NIH the nations medical research agency includes  Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic clinical and translational medical research and is investigating the causes treatments and cures for both common and rare diseases. For more information about NIH and its programs visit  https NIHTurning Discovery Into Health Reference Najm et al. Drugbased modulation of endogenous stem cells promotes functional remyelination in vivo Nature April  ."