New research points to possible treatments for muscle wasting disorders offers exciting news because FHL1 appears to modulate muscle mass and strength enhancement. The protein partners with and activates the transcription factor, NFATc1. Encouraging this partnership might provide a possible treatment for muscle wasting disorders. The article will appear in the December 15, 2008 issue of The Journal of Cell Biology (JCB).

Mutations in FHL1 are present in several myopathies, including reducing-body myopathy (RBM), but until now, both the molecular mechanisms causing the disease, and the regular function of FHL1 in healthy tissue, remained unknown.

To address this, Cowling et al. overexpressed FHL1 in both transgenic mice and cultured myoblasts. The mice developed skeletal muscle hypertrophy, and showed increased strength and endurance. Overexpression in myoblasts also increased cell fusion, resulting in hypertrophic myotubes. These phenotypes are similar to those caused by the calcineurin/NFAT pathway and, indeed, inhibiting calcineurin blocked the effects of FHL1 overexpression in vitro. The authors showed that FHL1 binds to and enhances the transcriptional activity of NFATc1 in vitro and in vivo.

So what goes wrong when FHL1 is mutated? In RBM, mutant FHL1 accumulates in cytoplasmic aggregates called reducing bodies, probably as a result of misfolding. When these mutants were expressed in cultured myoblasts, they also aggregated, and did not induce hypertrophy. Cowling and colleagues found that NFATc1 was sequestered to the aggregates, and was therefore unable to activate its target genes.

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Article adapted by Sandco from original press release.
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Contact: Rita Sullivan
Rockefeller University Press

Cowling, B.S., J Cell Biol. 2008 Dec 15;183(6):1033-48

Athletes and bodybuilders use creatine to increase muscle mass , decrease fat free mass and improve exercise performance. The latest creatine research shows people with muscular dystorphies increase strength and reduce fat-free mass taking creatine.

Muscle strength increased by an average of 8.5 percent among people taking creatine, compared to those who did not use the supplement, according to a recent review of studies. Creatine users also gained an average of 1.4 pounds more lean body mass than nonusers.

The evidence from the studies “shows that short- and medium-term creatine treatment improves muscle strength in people with muscular dystrophies and is well-tolerated,” said lead reviewer Dr. Rudolf Kley of Ruhr University Bochum in Germany.

The review appears in the latest issue of The Cochrane Library, a publication of The Cochrane Collaboration, an international organization that evaluates medical research. Systematic reviews draw evidence-based conclusions about medical practice after considering both the content and quality of existing medical trials on a topic.

Creatine (creatine monohydrate) is used by muscle tissue in the production of creatine phosphate, which forms the source of energy working muscles use called adenosine triphosphate (ATP).[1] [2] Low levels of creatine have been associated with rheumatoid arthritis, chronic circulatory and respiratory diseases, as well as several muscle diseases, like Duchenne muscular dystrophy.[3]

People with muscular dystrophies can have lower-than-normal levels of creatine, along with increasing muscle weakness as their disease progresses. Since some studies suggest that creatine improves muscle performance in healthy people, many researchers have reasoned that it might be helpful in treating muscle disease.

The Cochrane researchers reviewed 12 studies that included 266 people with different types of muscular dystrophy. People in the studies who took creatine supplements used them for three weeks to six months.

In muscular dystrophies, the proteins that make up the muscles themselves are either missing or damaged. In a related group of disorders called metabolic myopathies, the chemicals that help muscles operate go awry.

Although creatine seemed to help many patients with muscular dystrophies, those with metabolic myopathies gained no more muscle strength or lean body mass than patients who did not use the supplement.

The reason for the contrasting results — creatine’s “fairly consistent” effects in muscular dystrophy and lack of effectiveness in metabolic diseases — is “not entirely clear,” Kley said, calling for more research on treatment for metabolic disorders.

The review was supported by the Neuromuscular Center Ruhrgebiet/Kliniken Bergmannsheil, at Ruhr-University Bochum and the Hamilton Health Sciences Corporation, in Canada. Kley and colleagues have each participated in trials of creatine treatment for muscle disorders, although none of the studies was sponsored by a maker of creatine.

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Article adapted by Sandco from original press release.
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FOR MORE INFORMATION
Health Behavior News Service: hbns-editor@cfah.org

Kley RA, Vorgerd M, Tarnopolsky MA. Creatine for treating muscle disorders. Cochrane Database of Systematic Reviews 2007, Issue 1.

The Cochrane Collaboration is an international nonprofit, independent organization that produces and disseminates systematic reviews of health care interventions and promotes the search for evidence in the form of clinical trials and other studies of interventions. Visit http://www.cochrane.org for more information.