A virus with a new stuffing
First steps to treat muscular dystrophy with gene therapy have been successful. With the help of a modified virus, a gene was transported into the muscles of mice, which forms a protein that is missing in sick people. Scientists at the University of Michigan have developed a viral vector that has been used to treat mice suffering from muscular dystrophy. The vector delivered the gene for the production of dystrophin, a protein important for the normal maintenance of muscle tissue, into the muscles of adult mice.
The secret: an ordinary virus whose natural genetic material has been completely removed to make room for the dystrophin gene. The result: dystrophic mice with muscles that produced high levels of the normal dystrophin protein for several months.
"We induced expression of the full-length dystrophin protein for at least three months in the muscles of adult mice suffering from Duchenne muscular dystrophy," said Jeffrey S. Chamberlain, professor of human genetics at the University of Michigan Medical School "We have demonstrated that mice can incorporate the gene from our viral vector into their muscle tissue. It's an encouraging result, but it's not a cure."
At this week's Human Genetics Meeting, Chamberlain presented new findings from ongoing research at the University of Michigan aimed at developing an effective gene therapy for muscular dystrophy.
Duchenne muscular dystrophy is a genetic disease affecting one in 3,500 men. It is caused by mutations in a very large, complex gene. It is the largest gene identified to date, making it very difficult for researchers to develop an effective gene therapy for this disease. How severe the symptoms appear depends on how much dystrophin expression is weakened. Without dystrophin, children suffering from this disease gradually lose muscle tissue and eventually die of heart or lung failure between the ages of 20 and 30.
For seven years, Chamberlain and his colleagues have been trying to overcome the technical problems standing in the way of an effective gene therapy treatment for muscular dystrophy. Recent work has focused on developing modified adenoviruses - this is the same type of virus that causes the common cold. Because adenoviruses have the natural ability to invade muscle cells, they make excellent vectors for the dystrophin gene.
"Unfortunately, dystrophin is too large to fit in a conventional adenovirus," Chamberlain said ingest dystrophin virus."
Chamberlain calls his solution an "empty virus." Removing genes normally found in the virus makes room for the full version of dystrophin prevent the body's immune system.
So far, Chamberlain has only tested the virus in one strain of dystrophic immunodeficient mice. This allowed him to test the stability of the vectors without worrying about the immune response.
"The results indicate that these new voided viruses are very stable in adult animals. This allows dystrophic animals to be effectively supplied with dystrophin for longer periods of time," Chamberlain said to test normal immune response.
"If our adenovirus vector is able to produce an equally high level of dystrophin expression in immunologically normal mice, we may be able to perform limited clinical testing in humans."
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