Biglican – a cure for Duchenne myodystrophy?

Duchenne myodystrophy is a severe genetic disease. Progressive muscle dysfunction leads to disability, and then to paralysis of the respiratory muscles. American scientists have studied a protein that can partially compensate for damage to muscle tissue, and have developed a way to stimulate its synthesis. The method showed good results on sick mice.

Dystrophin is a protein that maintains the integrity of the muscle cell membrane. It is encoded by a gene located on the X chromosome, and therefore Duchenne myodystrophy, a disease in which dystrophin synthesis is disrupted due to mutation, usually develops in boys. The frequency of the disease may vary in different countries. On average, 1 boy out of 3500 thousand is sick.

Today there is no effective way to treat this disease. Great hopes are pinned on gene therapy – the artificial introduction of a healthy copy of a gene into muscles – but choosing a reliable and safe means of delivering genetic information to cells takes a long time, and therefore it is unlikely that this approach will enter clinical practice in the next ten years.

A group of researchers led by Justin Fallon worked with a dystrophin analog, the protein atrophin. It was known that this protein can partially compensate for the lack of dystrophin in muscle cells and slow down the development of the disease. However, it remained unclear how to stimulate the synthesis of atrophin in the cell. Normally, it is produced at the stage of embryonic development, and then its synthesis practically stops.

Several research groups are working on this task in parallel, and a number of drugs that stimulate the production of atrophin have already been proposed. It is unclear which of them will be able to withstand clinical trials. In a study published in the Proceedings of the National Academy of Sciences (Biglycan recruits utrophin to the sarcolemma and counters dystrophic pathology in mdx mice), scientists suggest using biglycan, a small glycoprotein (a complex of protein and carbohydrate), a component of the extracellular matrix, for this purpose.

Scientists created transgenic mice that did not produce biglican, and demonstrated that their atrophin synthesis was also disrupted. When the animals were injected with human biglican synthesized by transgenic bacteria, the level of atrophin was restored.

In the next series of experiments, the scientists worked with mdx mice. In these mice, dystrophin synthesis is disrupted (a cross–section of muscle tissue in the upper image) - just like in people with Duchenne myodystrophy. With the introduction of biglican (and an increase in the level of atrophin), these mice became stronger, and the muscle structure approached normal (bottom picture). Scientists have also shown that for three months of treatment, the drug did not cause serious side effects.

Brown University, which has discovered the possibility of using biglican for the treatment of myodystrophy, has created the company Tivorsan Pharmaceuticals, which will prepare the drug for clinical trials.

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18.01.2011