The identification of genetic mutations that underlie the many forms of congenital muscular dystrophy (CMD) has allowed scientists to begin to unlock the secrets of these diseases and to consider ways in which they might be treated.
Most MDA-supported researchers now working in CMD are studying the effects of CMD-causing mutations, particularly those in proteins known as collagen 6 and the laminin alpha 2 chain that forms part of the laminin 2 (merosin) protein.
Scientists are trying to figure out how mutations in these genes affect the proteins made from them and how those protein effects lead to the symptoms of CMD in muscle and sometimes other tissues.
In some cases, researchers have found, it may be possible to get around the basic genetic problem without actually replacing or repairing the specific gene involved.
For instance, if the mechanics of glycosylation ("sugar coating") of the dystroglycan protein can be unraveled, it may prove possible to improve this process despite the presence of a genetic abnormality. For example, laboratory experiments suggest that increasing the amount of a protein called LARGE in muscle tissue may be helpful in any form of CMD in which dystroglycan sugar coating is deficient, even if LARGE is already present in normal quantities.
MDA-supported scientists are also conducting laboratory experiments to see whether laminin chains other than the missing laminin alpha 2 chain can substitute for laminin alpha 2 in merosin-deficient CMD. They suspect using a different laminin chain from the one that's actually missing may be better tolerated by the immune system. (The immune system sometimes can't tolerate the sudden appearance of a previously missing protein.)
In some cases of Ullrich CMD, a genetic mutation in one of the collagen 6 genes causes the protein to take on a toxic function. In these cases, it's necessary to devise a therapy that will block this toxic activity, rather than raise the level of a deficient protein. Therefore, some MDA researchers are using a strategy called RNA interference in experimental animals with collagen 6-related CMD to try to "knock down" the toxic genetic instructions and alleviate disease symptoms.
Still other lines of research include improving skeletal muscle growth, repair and survival in general even though a CMD-causing gene defect is present.
For more about research in CMD, see Connecting the Dots: Research shows congenital MDs have roots outside cells.