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Growing New Muscle Amphibian Style

Taking a cue from the lowly salamander, a group of researchers led by Peter Schultz of the Scripps Research Institute in La Jolla, Calif., has isolated a compound that causes mature mouse muscle cells to disassemble into many pieces, divide into new muscle cells and then grow again. The new compound has been given the name myoseverin.

This is the same mechanism used by amphibians (like salamanders) to create new muscle after the amputation of a limb. Until Schultz announced his findings, scientists didn't think the same process could create new muscle from the cells of mammals (warm-blooded animals).

The discovery of myoseverin is owed to a relatively new process called combinatorial chemistry that yields large numbers of artificial compounds, which are then screened for a specific property, such as the ability to create new muscle. Myoseverin seems to work by stimulating genes known to be involved in tissue regeneration and wound healing.

This preliminary research, reported in the March issue of Nature Biotechnology, may lead to novel ways to stimulate muscle regrowth in degenerative diseases.

NIH Launches Clinical Trials Database

In February, the National Institutes of Health launched a database that, so far, contains information about some 4,000 clinical trials now under way, most of which are funded by NIH. In the future, the database will include trials funded by private industry and non-NIH federal agencies. The database is on the Web at http://clinicaltrials.gov. It can also be reached through the National Library of Medicine's Web site at http://www.nlm.nih.gov.

Specific information about the new database and general information about clinical trials can be requested by phone at (301) 496-6308 or via e-mail to publicinfo@nlm.nih.gov.

Enzyme Blockers May Prove Useful Against Inflammatory Myopathies

Polymyositis (PM) and sporadic inclusion body myositis (sIBM) are autoimmune diseases that occur when the body's immune system mistakenly targets muscle tissue for destruction. These diseases may cause weakness, pain and fatigue, and have a fluctuating course.

Researchers believe that much of the muscle inflammation that occurs in these diseases is mediated by a type of immune cell called a T cell. Under normal circumstances, T cells destroy other cells in the body that have been invaded by viruses or bacteria. In the inflammatory myopathies, however, T cells target healthy muscle cells.

In order to trigger an inflammatory response, T cells must first leave the bloodstream and make their way to the affected organ. Some researchers see this requirement as a target at which to aim therapies against inflammatory muscle diseases.

Recently, Young-Chul Choi and Marinos Dalakas of the National Institute of Health found evidence that enzymes called matrix metalloproteinases, or MMPs, play a role in helping destructive T-cells leave the bloodstream and stick to muscle cells in PM and sIBM. These same enzymes may play a role in other autoimmune diseases such as multiple sclerosis, Guillain-Barré syndrome and rheumatoid arthritis.

The researchers conclude that MMP blockers might be used to prevent T cells from invading the muscle tissue, and should be considered in clinical trials of patients with inflammatory myopathies. The work appeared in the Jan. 11 issue of Neurology.

Gentamicin Trial Opened to Those With LGMD

Last year, MDA-funded researchers at the University of Pennsylvania in Philadelphia discovered that the antibiotic gentamicin allowed the muscle cells of mice with Duchenne muscular dystrophy to "read through" a specific type of genetic error and make a functional dystrophin protein. Soon after, a clinical trial was initiated at Ohio State University in Columbus to test genta-micin in boys whose DMD is due to the same type of genetic error (a premature stop codon). For more information, see Quest, vol. 6, no. 4, Research Updates.

Now neurologist Jerry Mendell, the lead investigator for the trial, has amended the protocol to include those with limb-girdle muscular dystrophy (LGMD) due to a premature stop codon. If you're interested in participating, you'll need to have your genetic mutation analyzed to determine if you have a premature stop codon.

For more information about trial participation and the mutation analysis process, contact the Ohio State University clinical trial coordinator at (614) 293-9016.

Correction
In Quest vol. 7, no. 1, information on a study of glutamine and creatine in Duchenne muscular dystrophy was incorrect. The two substances are being separately evaluated at Children's National Medical Center in Washington and elsewhere.