Duchenne muscular dystrophy, which afflicts thousands of American males, is the most common and devastating of all muscle-wasting diseases. Muscle deterioration starts in childhood and becomes progressively worse. Victims rarely survive beyond early adulthood. At present there is no cure the disorder. Although scientists have been trying to understand the causes of Duchenne's and to find an effective treatment many years, they now appear to be on the brink of two achievements of unprecedented importance. One is identification of the protein responsible the disease. other is isolation of the gene on the X chromosome codes the culprit protein, the gene affected sons inherit from their unaffected mothers. Identification of the protein and gene would be the greatest research coup since the disease was first described in 1861, declares Melvin Moss, director of research the Muscular Dystrophy Association in New York City. The reason is once scientists determine the basic cause of the disease, rational approaches to therapy could be undertaken. research appears to be bringing scientists close to identification of the Duchenne protein comes from Edward Rosenmann and his biochemistry team at the University of Manitoba in Canada. As they reported in the Aug. 5 NATURE and at the International Congress on Neuromuscular Diseases in Marseilles, France, in September, they have found a particular protein is missing in cells from Duchenne patients. is the first time a protein abnormality has been noted in cells from Duchenne patients. It's conceivable the missing protein is the one responsible Duchenne. A complex scenario led Rosenmann and his team to the missing Although the major pathological changes in Duchenne occur in skeletal muscle, minor ones have also been detected in other parts of the body, including connective tissue cells called fibroblasts. These quirks probably all caused by the same gene and protein because all cells in a Duchenne patient's body contain essentially the same genetic material. Thus, if a protein defect could be determined in a non-muscle cell from a Duchenne patient, it might well be the same flaw makes muscle cells in the patient dystrophic. Fibroblasts easier to obtain than muscle cells are, and they easier to study. Rosenmann and his colleagues decided to look the responsible protein there. They took fibroblasts from Duchenne patients and from healthy subjects and attempted to see whether there was any difference in protein composition. They found one -a protein of about 56,000 daltons in molecular weight was present in cells from healthy subjects but not in cells from patients. This is the first time, Rosenmann told SCIENCE NEWS, that differences between normal and dystrophic cells can be attributed to one protein. He cautions, though, for the moment we cannot really say this is the primary defect responsible the dystrophic condition. Still, he and his colleagues hope it is and will try to collect more evidence to prove it. It's conceivable the missing protein is an enzyme because enzyme deficiencies now known to underlie three inherited muscle diseases other than Duchenne. imminent prospect of isolating the gene makes the culprit Duchenne protein comes from a number of genetic teams working independently yet cooperatively. What is remarkable about their efforts is they confident they will be able to isolate the gene and even agree on when they will do so. They estimate they will have a genetic marker the gene is, genetic material close to the gene-in hand within the next 18 months and the gene itself located within the next four or five years. reasons, explains Uta Francke of Yale University School of Medicine, are all the tools available, there is enough interest, and there enough good people working on the project. Although there variations in their tactics, their thrust takes a basic form. First, blood cells taken from the normal, healthy population. DNA is extracted from the cells, and enzyme splicing is used to generate large numbers of specific DNA fragments. Those DNA pieces on the short arm of the X chromosome the ones of interest because microscopic evidence obtained during the past several years suggests the Duchenne gene is in the middle of the short arm. Then the geneticists look variations in the pieces. If such variations exist, the geneticists take genetic material from the blood cells of Duchenne patients and their families and analyze it to see if there is any particular variation is always present in Duchenne patients and Duchenne carriers. (Preliminary evidence this is the case, in fact, was reported in the Nov. 4 NAruRE by Robert Williamson and colleagues at the University of London.) Such a gene variation would serve as a genetic marker Duchenne muscular dystrophy. In .4 2 .3 2 .2
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Aug 3, 2021
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