GENE THERAPY OFFERS HOPE FOR
CONGENITAL MUSCULAR DYSTROPHY

Scientists have shown that an innovative gene therapy strategy holds promise for treating congenital muscular dystrophy (CMD).

CMD refers to a group of muscular dystrophies that manifest at birth, and cause a variable degree of muscle weakness and wasting. In the most severe cases, affected individuals never gain the ability to walk, and die before age 30.

The most common form of CMD (called merosin-deficient congenital muscular dystrophy) is caused by flaws in the laminin alpha2 gene, which encodes a protein that's part of a larger protein complex called laminin. Laminin (sometimes called merosin) normally serves as a linchpin in a protein scaffold that surrounds and supports muscle cells, and when it's defective, the scaffold and the affected muscle fall apart.

This type of CMD ranges in severity from mild to extreme.

Theoretically, scientists could treat the disease by supplying an intact laminin alpha2 gene, but a group of European scientists has shown that it might be more effective to supply the gene for the protein agrin, an unrelated gene with a similar function.

In the Sept. 20 issue of Nature, the group reports that a miniaturized version of the agrin protein (called miniagrin) can substitute for laminin alpha2 and thus largely prevent CMD in laminin alpha2-deficient mice.

The mice were genetically engineered to overproduce miniagrin. But a potential treatment could provide people with CMD with virally delivered miniagrin or a drug that boosts the body's natural production of agrin, the group suggests.

These approaches would avoid potential immune reactions caused by giving the laminin alpha2 protein to someone whose body has never seen it, they say.

Previous studies by MDA grantees Kay Davies and Stephen Kaufman have shown that a similar approach holds promise for treating Duchenne muscular dystrophy. Kaufman, who's at the University of Illinois in Urbana, said the new study "adds to the potential for using complementary genes to provide a remedy for the defective genes that cause muscular dystrophy." Much work still needs to be done to develop the approach, he added.