Muscle diseases rare

NIH NewsBethesda, Md., Mon., Sept. 24, 2012 - Last week, researchers launched a Phase I clinical trial to evaluate the drug candidate DEX-M74 as a treatment for patients suffering from Hereditary Inclusion Body Myopathy (HIBM), a rare degenerative muscle disease. National Institutes of Health (NIH) scientists from the National Center for Advancing Translational Sciences (NCATS) and the National Human Genome Research Institute (NHGRI) will conduct the clinical trial at the NIH Clinical Center.

HIBM, also known as GNE myopathy, is a rare genetic disease with no available therapy. Disease symptoms emerge in adulthood and slowly lead to progressive muscle weakness. Most patients develop symptoms while in their early twenties and eventually require a wheelchair as their arm, hand and leg muscles weaken. Mutations in the GNE gene cause HIBM by producing low sialic acid levels in muscle proteins, which scientists think contributes to the symptoms of muscle weakness. Normally, GNE produces an enzyme that produces sialic acid in the body, a sugar important to muscle development and kidney function.

"This study marks an important milestone toward developing a treatment for an underserved patient population, and we would not be this far along had it not been for the teamwork and dedication of the researchers working on this collaboration, " said NCATS Director Christopher P. Austin, M.D., the newly appointed director of NCATS.

In 2007, Marjan Huizing, Ph.D., an associate investigator in NHGRI's Medical Genetics Branch, led a team of scientists in search of an HIBM treatment. They hypothesized that a compound called ManNAc, now called DEX-M74, might improve the low sialic acid levels that cause HIBM. DEX-M74 is a sugar converted by the body to sialic acid.

Huizing and colleagues conducted studies that showed the compound was effective in controlling sialic acid levels in a mouse model with a specific GNE mutation. The researchers published their findings in the June 2007 issue of the Journal of Clinical Investigation. Based on these results, they set out to evaluate the effects of DEX-M74 on progressive muscle weakness in HIBM patients. However, the project required additional funding for pre-clinical studies.

In 2009, NIH established its Therapeutics for Rare and Neglected Diseases (TRND) program, now part of NCATS, to facilitate the pre-clinical development of new drugs for these ailments. TRND scientists selected the development of DEX-M74 as a treatment for HIBM as one of its initial pilot projects. The collaboration includes TRND researchers, the laboratories of Marjan Huizing, Ph.D., and of William A. Gahl, M.D, Ph.D., principal investigator of NHGRI's Medical Genetics Branch, and New Zealand Pharmaceuticals Limited (NZP). NZP is manufacturing DEX-M74, which was developed by Drs. Gahl and Huizing and licensed from the NIH by NZP.

Neuroradiologic Findings in Rare Inherited Neurologic Diseases of Childhood: Muscle-Eye-Brain Disease, Mitochondrial Disorders and Infantile Onset Spinocerebellar Ataxia
Book (Department of Radiology, University of Helsinki)
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