November 29, 2007

Scientists Fix Muscle Relaxation in MMD Mice

Researchers at the Sen. Paul D. Wellstone Muscular Dystrophy Cooperative Research Center at the University of Rochester (N.Y.) and the University of Florida in Gainesville report that they’ve used a molecular strategy to restore normal muscle relaxation after contraction in mice with myotonic muscular dystrophy (MMD). The Wellstone Center is supported by the National Institutes of Health and has also received support from MDA.

Charles Thornton, who co-directs the MDA clinic at the University of Rochester Medical Center, coordinated the research team, which published its results online Nov. 15 in the Journal of Clinical Investigation.

The team, which also included MDA research grantee Maurice Swanson at the University of Florida, injected MMD-affected mice with a synthetic compound designed to change the way muscle cells interpret genetic information for constructing chloride channels, cellular tunnels through which chloride ions flow. The synthetic compound is known as an antisense oligonucleotide.

In MMD, a defect in a gene on either chromosome 19 (in type 1 MMD) or chromosome 3 (in type 2 MMD) causes a variety of muscle and other problems, including myotonia, the inability to relax muscles after contracting them. The myotonia, as shown in this study, is caused by an abnormally constructed chloride channel.

In recent years, studies by Thornton, Swanson and many others, have shown that an expanded section of DNA in either the DMPK gene on chromosome 19 or in the ZNF9 gene on chromosome 3 indirectly leads to errors in construction of the chloride channel and other cellular components and to the symptoms of MMD.

“The results of this work are an important step forward that should provide hope and encouragement to people with myotonic dystrophy and members of their families,” Thornton said. “Signs of myotonic dystrophy in the mice got better even after they had been present for a long time.”

Thornton noted that the antisense oligonucleotide they used has to be injected directly into muscle and that it would be better to design a compound that could be injected systemically to treat human MMD.

“The good results in lab testing give us strong motivation to find other drugs having a similar effect that could spread through the body,” he said.