Delivering the gene for the missing dystrophin protein to the muscles of children and young men with Duchenne muscular dystrophy (DMD) is one of several therapeutic avenues under intense investigation in this disease. However, the strategy has technical drawbacks, and some experts worry that introduction of a previously absent protein could provoke a dangerous immune response.
An alternative to replacing dystrophin is increasing levels of proteins patients already produce (and that their immune systems will likely accept) that may compensate for dystrophin's loss.
One such protein is utrophin, which occupies a position similar to dystrophin's near the muscle-fiber membrane but only in a small part of each fiber.
Now, MDA grantee Dongsheng Duan and colleagues at the University of Missouri-Columbia, who published their findings online Jan. 8, 2009, in Human Molecular Genetics, suggest that proteins called sarcoglycans, embedded in the muscle-fiber membrane near dystrophin, might also be compensatory in dystrophin deficiency.
When these investigators bred mice missing both dystrophin and the sarcoglycan proteins, they found the mice had a much more severe muscular dystrophy and a shorter life span than mice missing dystrophin alone.
Sarcoglycan protein levels are reduced in people with DMD to varying degrees, probably because the protein can't take its proper place in the membrane without guidance from specific parts of the dystrophin molecule.
The new findings led Duan and colleagues to speculate that variable levels of properly localized sarcoglycan proteins may account for some of the differences in severity and rate of disease progression among DMD patients, and that raising sarcoglycan levels might improve the prognosis in severe DMD.