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NIH-funded study identifies OTC compounds that may replace damaged cells

Two over-the-counter (OTC) drugs, an antifungal and a steroid, already on the market may potentially take on new roles as treatments for multiple sclerosis (MS), according to a study partially funded by the National Institute of Neurological Disorders and Stroke (NINDS), part of the National Institutes of Health (NIH).

In the NIH-funded study, researchers found that these drugs may activate stem cells in the brain to stimulate myelin producing cells and repair white matter, which is damaged in MS.

Oligodendrocytes, a type of neuroglia, lay down multiple layers of a fatty white substance called 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.

Adult brains contain oligodendrocyte progenitor cells (OPCs), which are found to multiply in the brains of multiple sclerosis patients as if to respond to myelin damage, but they are not effective in restoring white matter for unknown reasons.

Case Western Reserve School of Medicine associate professor and senior author of the study Paul Tesar said: "To replace damaged cells, the scientific 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.

"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 body’s ability to repair itself."

OPCs have been difficult to isolate and study, but Dr Tesar and his colleagues, in collaboration with Dr Robert Miller, 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 in particular, miconazole (an antifungal) and clobetasol (a steroid), screened in this study were obtained from a drug library maintained by NIH’s National Center for Advancing Translational Sciences (NCATS).

Dr Tesar’s team found that these two compounds stimulated mouse and human OPCs into generating myelin-producing cells.

NINDS program director Ursula Utz said: "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."