NEUROLOGY

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Drugs That Activate Brain Stem Cells May Reverse Multiple Sclerosis

 

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. It is unknown how myelin-producing 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 anti-inflammatory drugs, which help prevent the episodic relapses common in multiple sclerosis, but are less effective at preventing long-term disability. Experts 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 myelin-producing 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. As a result, according to a study published online in Nature (20 April 2015), two drugs already on the market — miconazole (an antifungal) and clobetasol (a steroid), may potentially take on new roles to stimulate OPCs to increase myelination as treatments for multiple sclerosis. OPCs have been difficult to isolate and study, but the authors have 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 NIH’s National Center for Advancing Translational Sciences (NCATS). All are approved for use in humans. After screening, the authors examined whether the drugs, when injected into a mouse model of multiple sclerosis, could improve re-myelination. 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 authors 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. According to the authors, off-label use of the current forms of these drugs is more likely to increase other health concerns than alleviate multiple sclerosis symptoms and they are actively working to have a safe and effective drug for clinical use.

 

The online version of this release contains an illustration of remyelination.

 

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.

 

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