Compounds Up Utrophin, Help DMD-Affected Mice

Sabine de la Porte, an MDA research grantee in France, and colleagues have demonstrated that mice with a disease resembling Duchenne muscular dystrophy (DMD) benefit from treatments that increase utrophin, a protein similar to dystrophin, which is missing in DMD.

The researchers, who published their findings in the October issue of Neurobiology of Disease, say that treating the mice with L-arginine resulted in a twofold to threefold increase in utrophin levels in the muscles of the mice. Molsidomine, another compound, had similar effects.

The study’s authors say they believe both compounds raise utrophin levels by increasing production of nitric oxide (NO). Bernard Jasmin, an MDA grantee at the University of Ottawa (Canada), says preliminary observations in his lab support these findings.

In another study, published online Aug. 22 in Muscle & Nerve, MDA-supported Elisabeth Barton at the University of Pennsylvania in Philadelphia also noted the benefits of L-arginine in DMD-affected mice.

Her group found that when L-arginine was injected into the abdomens of the mice or delivered via an implanted pump for at least four weeks, it increased levels of utrophin and improved resistance to contraction-related muscle fiber injury.

The Philadelphia investigators say they think L-arginine may have activated muscle fiber repair mechanisms, as well as stabilizing their membranes and perhaps improving their handling of calcium.