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Gene therapy for muscular dystrophy fixes frail muscle cells in animal model, Stanford study finds

did not look at whether the introduced dystrophin spread along the entire length of the muscle cell, which can be many millimeters long in mice or inches long in humans.

In the upcoming paper Bertoni used a standard gene therapy method to introduce two genes - dystrophin and a gene that makes a glowing protein - into mice with a mouse version of muscular dystrophy. She found that in mice producing insufficient dystrophin, she could see the glowing protein slowly leak out of the cell. This leakiness is a sign that the cell is not healed. In contrast, when she used Calos' gene therapy technique to introduce the genes, the muscle cell contained high levels of dystrophin distributed along the length of the cell and the glowing protein stayed within the cell, suggesting that the abundant dystrophin repaired the ailing muscle.

"If you have a single cell that's a foot long and you only correct a few inches, you've done very little," Rando said, "Whereas if you correct it from end to end, you truly cure the disease in that cell."

Both Rando and Calos point out that the road to a gene therapy cure for muscular dystrophy is still a long one. However, Calos is confident that her technique will be a part of the journey towards a cure for the disease and for other diseases such as hemophilia and the skin disease, epidermolysis bullosa. Early trials using her approach have looked promising in animal models of both of these diseases.

"I think our approach has a lot of potential to overcome issues that have slowed the field of gene therapy," Calos said.

Calos said her approach has two advantages: one is that in her method the gene gets inserted directly into the cell's own DNA, which is why the correction is permanent. In some other methods the gene stays outside the DNA and slowly breaks down. The second advantage is that her method doesn't rely on a virus to disperse the DNA and therefore avoids some of the issues, including cancer and an
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Source:Stanford University Medical Center


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