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New Therapeutic Insight into Duchenne Muscular Dystrophy

04/01/2007

New Therapeutic Insight into Duchenne Muscular Dystrophy

In the April 1st issue of Genes & Development, Dr. Bruce Spiegelman (Dana Farber Cancer Institute) and colleagues identify a key genetic component of and possible therapeutic target for Duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD) is the most common form of muscular dystrophy, affecting about 1 in 3000 males each year. It is an X-linked recessive disease, in which mutations in the dystrophin gene causes progressive and degenerative muscle weakness. DMD is generally lethal by age 30.

Dr. Spiegelman and colleagues found that a protein called PGC-1alpha regulates the point of connection between the end of a motor neuron and a muscle fiber – what researchers call the “neuromuscular junction.” Electrical impulses travel through the neuromuscular junction, ultimately causing the muscle to contract. Previous research has shown that PGC-1alpha expression is induced by physical exercise and motor neuron activity, and mediates the anti-atrophic effects of nerve activity on muscle mass.

Dr. Spiegelman and colleagues analyzed the function of PGC-1alpha in a mouse model of DMD. They found that PGC-1alpha activates the expression of several genes that are aberrantly inactivated in DMD. In fact, by inducing PGC-1alpha expression in these transgenic mice, the scientists were able to improve DMD symptoms.

"These data clearly show that experimental elevation of PGC-1 alpha has therapeutic promise in an animal model of Duchene’s muscular dystrophy. We hope this will lead eventually to therapeutics for a terrible disease for which there is no effective treatment at the present time,” explains Dr. Spiegelman.

To Sleep, Perchance to Dream: New insight into melatonin production

In the April 1 issue of G&D, a Korean research team led by Dr. Kyong-Tai Kim (Pohang University) describes how melatonin production is coordinated with the body’s natural sleep/wake cycles.

Melatonin is a hormone produced by the pineal gland in the brain, which helps to regulate our bodies’ circadian rhythm (the roughly-24-hour cycle around which basic physiological processes proceed). Normally, melatonin production is inhibited by light and enhanced by darkness, usually peaking in the middle of the night. Melatonin’s expression pattern is mimicked by a protein called AANAT, which is a key enzyme in the melatonin biosynthesis pathway.

Dr. Kim and colleagues uncovered the mechanism of rhythmic control of AANAT mRNA translation, and thereby melatonin synthesis. The researchers found that rodent AANAT mRNA translation is mediated by IRES elements in the 5’ end of the transcript, through binding of another protein, called hnRNP Q. In fact, siRNA knock-down of hnRNP Q reduced AANAT and melatonin production under nocturnal conditions.

Genes & Development is a publication of the Cold Spring Harbor Laboratory Press. The Cold Spring Harbor Laboratory is a private, non-profit, basic research and educational institution. Scientists at the Laboratory conduct groundbreaking research in cancer, neurobiology, plant molecular genetics, genomics and bioinformatics. The Laboratory is recognized internationally for its educational activities, which include an extensive program of scientific meetings and courses that attract more than 8000 scientists to the campus each year. For more information about the Cold Spring Harbor Laboratory, visit http://www.cshl.org or call the Department of Public Affairs at (516) 367-8455.

Contact:
Heather Cosel-Pieper
Genes & Development
Cold Spring Harbor Laboratory
tel. (516) 422-4018
fax (516) 422-4093



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