By: Megan Brooks – May 01, 2015
Research designed to repurpose approved drugs in spite of new uses has turned up pair drugs that may take on renovated roles as novel treatments for multiple sclerosis (MS).
A team of US scientists has ground that the antifungal miconazole and the steroid clobetasol stimulate mouse and human oligodendrocyte progenitor cells (OPCs) into generating myelin-producing cells in agri~.
Systemic delivery of the drugs significantly increased the designate by ~ of new myelinating oligodendrocytes and enhanced remyelination in a lysolecithin-induced mouse model of focal demyelination.
Administering every one of the two drugs at the peak of malady in an experimental autoimmune encephalomyelitis look closely model of chronic progressive MS led to “wonderful” reversal of disease severity, with nearly all of the animals regaining the employment of their hind limbs, they official communication.
The results were published online April 20 as a letter in Nature.
A Paradigm Shift
Immune response assays suggest that miconazole functions speedily as a remyelinating drug with none effect on the immune system, during the time that clobetasol is a potent immunosuppressant while well as a remyelinating agent, the authors official communication. Mechanistic studies hint that miconazole and clobetasol derivative in OPCs through mitogen-activated protein kinase and glucocorticoid receptor signaling, respectively.
“To replace damaged cells, the according to principles field has focused on direct transplantation of prow cell-derived tissues for regenerative healing art, and that approach is likely to supply enormous benefit down the road,” Paul J. Tesar, PhD, co-senior author, from Case Western Reserve School of Medicine in Cleveland, Ohio, commented in a information release.
“We asked if we could declare by verdict a faster and less invasive draw near by using drugs to activate congenital nervous system stem cells and from father to son them to form new myelin. Our most remote goal was to enhance the body’s ability to repair itself,” Dr Tesar afore~.
The ability of miconazole and clobetasol to advance the regenerative capacity of stem cells in the grown up nervous system “truly represents a example shift in how we think all over restoring function to multiple sclerosis patients,” declared co-senior author Robert H. Miller, PhD, a clause of the neurosciences faculty at Case Western Reserve.
The researchers be suitable to on miconazole and clobetasol as in posse MS treatments by screening hundreds of approved compounds in a physic library maintained by the National Center since Advancing Translational Sciences, part of the National Institutes of Health. Dr Tesar and colleagues mark out to expand the library of drugs screened contrary to OPCs in the near future to become identical other promising compounds.
This research “opens up one exciting new avenue of therapy progress to maturity for myelin disorders such as multiple sclerosis,” Ursula Utz, PhD, program adviser at the National Institute of Neurological Disorders and Stroke, said in a news release.
Dr Tesar and his colleagues caution that the be in action is preliminary and much more research is needed before miconazole and clobetasol can be tested in MS clinical trials. Both agents are publicly only approved for topical use, and their security when administered in other forms in humans is without the knowledge of.
The researchers conclude that “significant optimization of dosing, delivery, and potentially chemical structure will have ~ing required to enhance the on-target pharmacology in OPCs while diminishing at all potential off-target side effects. However, the aptitude of miconazole and clobetasol to crusty the blood–brain barrier raises the exciting potentiality that these drugs, or modified derivatives, could advance into clinical trials for the commonly untreatable chronic progressive phase of MS.”
This research was supported by the National Institutes of Health, New York Stem Cell Foundation, Myelin Repair Foundation, and the Mt. Sinai Health Care Foundation. Philanthropic have also came from the Goodman Trust; Cleveland Foundation; and the families of Bruce and Brenda Goodman, Lionel and Irmgard Long, and Albert and Norma Geller. The authors be under the necessity disclosed no relevant financial relationships.
Nature. Published online April 20, 2015. Abstract
Source division :http://www.medscape.com/viewarticle/844076
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