Rockefeller University scientists say that an overlooked and undervalued protein, sarcospan, may ameliorate the most severe form of muscular dystrophy if added to muscle cells.
The researchers write in their study report that in Duchenne muscular dystrophy (DMD), the mutated dystrophin protein fails to anchor correctly to its membrane glycoprotein complex, causing muscle cells to experience severe contraction-induced damage.
AdvertisementThe say that sarcospan is part of the anchoring complex, but because mice without sarcospan do not seem any worse for its absence, it has not received much attention to date.
According to them, sarcospan's structure suggests that it may help stabilize the membrane complex, a reason why they decided to test the effects of increasing the protein's expression in a DMD mouse model.
The researchers say that increasing the expression of sarcospan did not improve the dystrophin-glycoprotein interaction, but surprisingly coaxed a dystrophin relative called utrophin to spread out on the muscle membrane.
They have revealed that utrophin is normally restricted to the neuromuscular junction, where it serves a role similar to that of dystrophin.
The extra sarcospan prompted higher levels of utrophin in the cell, but not by increasing its expression.
Sarcospan instead stabilized extrajunctional utrophin complexes, which normally form early in development and then disappear after the first few weeks of life.
During the experiments, the researchers observed that mouse muscle cells were protected by sarcospan.
They say that the true importance of their findings will lie in its potential for human therapeutics, specifically gene therapy.