New gene treatments for muscular dystrophy?

Two new studies promise new treatments for the muscular dystrophies, a group of genetic conditions that cause progressive muscle weakness. Italian researchers have combined stem cell and gene therapy techniques to successfully treat mice with symptoms of limb-girdle muscular dystrophy, while a UK group has used a novel form of gene therapy to treat mice missing the gene involved in Duchenne muscular dystrophy. Both groups, however, stress that more work is needed before the new therapies can be tested in humans.

Scientists at the Stem Cell Research Institute in Milan and the University of Rome used a type of fetal stem cell called mesoangioblasts to treat mice lacking the alpha sarcoglycan gene, the gene involved in limb-girdle muscular dystrophy. The team used gene therapy techniques to deliver healthy versions of the alpha sarcoglycan gene to the stem cells, which they then injected into the mice. Three months later, they found that the alpha sarcoglycan gene was present and 'switched on' in the muscles of the treated mice, and their muscles had been strengthened by the production of the resulting protein. 'The muscle cells of a dystrophied mouse are extremely weak, but a cured mouse recovered almost all its strength' said study author Roberto Bottinelli. But team leader Giulio Cossu was anxious not to raise hopes ahead of time, saying: 'this is an important result, but this is still not the therapy, for mice or humans'. One problem is the availability of the versatile mesoangioblast stem cells, which have so far only been identified in fetuses. The scientists published their findings in the journal Science.

Meanwhile, scientists based at the UK's Medical Research Council's Clinical Sciences Centre have used a type of gene therapy to treat mice with symptoms of Duchenne Muscular dystrophy (DMD). This incurable genetic condition, which affects mainly boys, is usually life-threatening by the time the patient reaches their early twenties. The researchers used RNA, a chemical relative of DNA involved in translating genes into proteins, to repair the dystrophin gene - which, when it is missing or faulty, causes DMD. Previous gene therapy attempts to treat DMD have run into problems because of the unusually large size of the dystrophin gene. This time, the scientists injected small pieces of RNA into the muscles of the mice, where it 'edited out' the effects of the faulty dystrophin gene. Qi Long Lu and colleagues treated more than 30 mice with the RNA snippets plus a detergent, which helped the RNA get into the muscle cells. Three weeks later, dystrophin protein levels had increased and the muscle strength of the mice had returned to 70 per cent of normal. However, the effects wear off after three months, so any attempt at using the therapy in humans would require regular injections, says Long Lu. The findings were reported in the journal Nature Medicine.