Antibiotic Helpful in DMD Mouse Model
NIAMS-funded scientists at the University of Pennsylvania have successfully applied the common antibiotic gentamicin to restore function of the protein dystrophin in mouse models of Duchenne muscular dystrophy (DMD). It is the absence of dystrophin that is responsible for this genetic muscle-wasting disease that affects 1 in 3,500 boys. The discovery, say the scientists, may pave the way for a treatment in some human patients with DMD.
The work (J Clin Invest. 1999;104(4):1-7), cofunded by the Muscular Dystrophy Association and carried out under the direction of Dr. H. Lee Sweeney, took its cue from the known ability of a class of antibacterial antibiotics called amino-glycosides to suppress certain gene sequences, called "stop codons," that inhibit protein production. The scientists tested a specific aminoglycoside, gentamicin, on cultured muscle cells from the mdx mouse an animal model for DMD that has a stop codon in the gene for dystrophin. The resulting restoration of dystrophin in cultured cells encouraged the researchers to try the antibiotic on the mice themselves. The result: dystrophin was restored to the cell membranes of all the striated mouse muscles they examined. Furthermore, the treatment afforded the muscles protection against injury.
"It appears that we may be witnessing the unfolding of a translational triumph in medical research from culture dish to mouse and, hopefully, to human treatment," says NIAMS director Dr. Stephen Katz.
Hip, Wrist Fractures Linked To Chromosome 19 Gene
Osteoporotic hip and wrist fractures a common feature on the landscape of older Americans may be partially rooted in a gene on chromosome 19, according to a study funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Scientists led by Dr. Jane A. Cauley at the University of Pittsburgh have found that older women with the gene for apolipoprotein E (APOE*4) are at increased risk for hip and wrist fractures. Previous studies of this gene have also shown its association with common, late-onset forms of Alzheimer's disease and with osteoporosis in patients on dialysis.
The study (J Bone Min Res. 1999;14(7):1175-1181), cofunded by the National Institute on Aging and the National Heart, Lung and Blood Institute, showed that the risk of hip and wrist fracture for women age 65 and over with the APOE*4 gene was nearly twice that of those without the gene, even after making adjustments for bone density, cognitive level or tendency to fall. Women with at least one APOE*4 gene were more likely to have a maternal history of fracture after age 50.
"We have long suspected that these types of fractures are due to more than a single factor," said NIAMS director Dr. Stephen I. Katz. "Here we have evidence of a specific genetic influence at work even when weak bones and balance problems are not at issue."
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