New Therapy Substitutes Missing Protein in Those with Muscular Dystrophy

Duchenne muscular dystrophy is the most common and severe type of muscular dystrophy seen in children. This disease is a recessive X-linked trait, thus affecting mainly males, approximately 1 in 3500. The disease is characterized by the mutation of the gene DMD, which codes for the protein dystrophin. This protein is an important part of the framework in the cell membrane that holds the muscle tissue together. Thus the symptoms of this disease are muscle weakness, and the rapid progression of muscle degeneration. Currently the only treatment for this disease is corticosteroids, which are minimally effective and have severe side effects.

Cross-section of muscle (wild-type is normal muscle development)

(mdx is patient with muscular dystrophy)

However Professor James Ervasti from the University of Minnesota Medical School believe to have discovered a new therapy that shows potential to treat those with muscular dystrophy. The therapy includes injections of a protein called utrophin, which is a close relative of dystrophin, into the bloodstream. Researchers have currently used mouse models that were lacking in the protein dystrophin. These mice were injected with the protein utrophin that had been modified with a cell-penetrating tag known as TAT. The utrophin protein replaced the dystrophin in the cell membrane, and restored much of the strength of the muscle. This is the first study that has shown the viability of using this TAT-utrophin-based protein to treat the symptoms of muscular dystrophy. It is also thought that this therapy could assist in the treatment of cardiac muscle diseases that have resulted from the loss of dystrophin.

At the current time there are other therapies being developed using stem cell treatments, or delivering gene therapy to each individual muscle cell. Both these treatments show promise, but each has their limitations. From the mouse models it is shown that this method of protein replacement overcomes the limitations of both these methods. Firstly the TAT-utrophin protein spreads throughout the body efficiently and is able to penetrate the cell wall of all muscle cells so that it can replace the dystrophin in the cell membranes, and restore structure. Secondly as utrophin is produced naturally in small amount in every cell of the body, there is no risk of the immune system fighting off a foreign substance in the body.

This treatment of injecting utrophin proteins to replace the missing dystrophin in muscle cells has shown to be effective in improving the structure of muscle cells in mice, However before a it is developed as a drug for patients, the therapy will need to be trialled on much larger mammals and lastly humans. If this treatment does become a drug, it will not be a cure for muscular dystrophy, but a therapy that will need to be administered on a regular basis, to simulate the bodies natural process of producing dystrophin.

Posted by: Tanya McDonald 42048879

University of Minnesota(2009, May 27). New Therapy Substitutes Missing Protein In Those With Muscular Dystrophy. Science Daily. Retrieved May 27, 2009, from http://www.sciencedaily.com/releases/2009/05/090526152713.htm