When a protein is unable to do its work, another can step in to take his place. That is the encouraging conclusion of researchers who discovered that overexpression of a protein called integrin reduces muscle degeneration in mice with symptoms of muscular dystrophy. The discovery, published in March 19 issue of Cell Biology Journal , using a day could identify drugs that slow the deadly disease.
Duchenne muscular dystrophy (DMD) hits a 3,500 boys worldwide. No other hereditary disease kills more children. Patients experience progressive muscle weakness and usually die before age 20. They lack a protein called dystrophin, which attaches muscle cells to external scaffolding between cells. Without this link, the muscle tissue disintegrates. Dystrophin but is not the only protein that anchor the cells to the extracellular matrix is known; and made a related protein, a 7 b 1 integrin. A team led by Stephen Kaufman at the University of Illinois at Urbana-Champaign wondered whether it could replace dystrophin.
The team began with mice that do not make dystrophin or a similar protein utrophin. These mice already produce about twice the normal levels of integrin in muscle tissue - probably to partially offset the loss of other proteins. Outfitting in mouse embryos with rat integrin gene, Kaufman doubled again their levels of integrin. The engineered mice lived an average of 38 weeks against 12 weeks for the dystrophic mice. They also showed less severely curved spines, greater mobility, and less weight loss.
parallel work of Kaufman findings at the University of Oxford that overexpression of utrophin also relieves muscle degeneration. The Oxford group is now testing drugs that could increase the levels of utrophin in the cells, and Kaufman hopes to follow the same route with integrin.
If these compounds are found, and patients receiving treatment at the first sign of weakness --generally 2 or 3 years - the strategy could work in theory explains cell biologist James Tidball University California, Los Angeles. But the disease is not progressing quite the same way in mice and people, Tidball warns. "It is difficult to say when or if [this research] would actually lead to a clinical application."
Related Sites
paper Summary in Journal cell biology
laboratory Stephen Kaufman
utrophin work at Oxford, described by the financing of the agency
UCLA Duchenne muscular dystrophy Research Center
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