DUCHENNE/BECKER AND UTROPHIN

A promising new avenue for Duchenne muscular dystrophy gene therapy has been opened following groundbreaking work by MDA- funded researcher Kay Davies of the University of Oxford in England. Her work involves using utrophin as a substitute for dystrophin, the protein which, when absent or defective, causes Duchenne and Becker muscular dystrophies.

Utrophin is made in large amounts during early development. Its production falls off later in development, though the gene remains intact. By artificially increasing the number of utrophin genes in mice which can't make dystrophin, Davies has shown that utrophin can substitute for dystrophin and apparently keep the mice from developing the symptoms of muscular dystrophy. Her work demonstrates that increasing the output from the normal utrophin gene (which is already present in someone with Duchenne or Becker dystrophy) could provide important therapy for these diseases.

At present, there are no drugs known to turn the utrophin gene back on effectively enough to accomplish this. However, the search for such drugs is now being pursued. In addition, Davies' work suggests that delivering the utrophin gene by the same method being studied for use with the dystrophin gene may also be effective.

SPINAL MUSCULAR ATROPHY

Spinal muscular atrophy was the focus of a recent workshop sponsored by MDA during the annual meeting of the Society for Human Genetics. At the workshop, researchers presented findings that shed more light on the genes involved in this disease. A few years ago, researchers found two genes they believed to be involved in causing this condition, one called SMN and the other NAIP. These genes lie next to each other on chromosome 5. Workshop leader and MDA researcher Arthur Burghes of Ohio State University in Columbus co-authored two recent papers reporting strong evidence that SMN, and not NAIP, is the gene responsible for SMA.

Another new MDA-funded study draws a clearer clinical picture of the course of disease for people with SMA types II and III. A group of researchers led by Barry Russman of the University of Connecticut Medical School in Newington recently developed guidelines for predicting the loss of muscle function over time. The study reports that both the age of onset of disease and the maximum function attained are important factors for predicting the rate of function loss.

ALS

In the October issue of Neurology, an MDA-funded study reports that daily oral doses of branched-chain amino acids aren't effective in slowing the progression of amyotrophic lateral sclerosis and, in fact, may hasten the decline of respiratory function.

Researchers are still looking for the cause of ALS in the 90 percent of people who don't have mutations in SOD1, the only known gene definitely linked to ALS. Among candidates have been the genes for neurofilaments, which are important structural components in nerve cells. Studies have shown that the structures formed by neurofilaments seem to be defective in many ALS patients, though until now it's not been clear whether this has been the cause of, or the result of, the nerve degeneration which lies at the heart of the disease. Now, a new MDA study has found that changes in neurofilament genes don't seem to cause ALS. The study reports finding that mutations in the neurofilament genes are just as common in people who don't have the disease.

MYASTHENIA GRAVIS

Recent research by MDA-funded scientist Premkumar Christadoss of the University of Texas in Galveston may signal the beginning of a new treatment for myasthenia gravis. Christadoss has shown that interferon-alpha effectively suppresses the equivalent disease in mice. Interferon-alpha is a naturally occurring chemical in the bloodstream which helps to regulate immune responses. His work shows that administering interferon-alpha can increase strength, and reduce the characteristic immune system signs of the disease. Christadoss is now organizing a human trial of interferon-alpha, which is already approved for use in several other diseases.