Genome editing treats muscular dystrophy in mice

Scientists in the USA have shown that the genome-editing technology CRISPR can improve muscle function in a mouse model of Duchenne muscular dystrophy (DMD).

This marks the first time that CRISPR has been successfully used to improve the symptoms of a fully developed mammal with a genetic disease. The studies were carried out by three independent research groups and were published side by side in Science.

'This is different from other therapeutic approaches because it eliminates the cause of the disease,' said Dr Eric Olson, who led one of the groups at the University of Texas Southwestern Medical Center.

DMD is a progressive muscle-wasting disease caused by mutations in the dystrophin gene. This leads to a deficiency of dystrophin protein, which is important in supporting the muscle fibres during contraction; without dystrophin, the muscle fibres become damaged and stop working.

As the DMD mouse model has a mutation in exon 23 of the dystrophin gene, the scientists designed a CRISPR system that would effectively delete this exon and result in a shorter but functional version of the dystrophin protein.

They packaged the system into a harmless virus called an adeno-associated virus, which was then injected into the DMD mice. This resulted in increased dystrophin expression in the heart and muscle of injected mice. Although the injected mice were significantly stronger than the non-injected mice, they were still weaker than healthy wild-type mice.

The ethical implications of CRISPR technology have been under much debate since Chinese scientists used it to genetically modify human embryos (see BioNews 799).

Dr Charles Gersbach, who led the research group at Duke University in North Carolina, said: 'Recent discussion about CRISPR to correct genetic mutations in human embryos has rightfully generated considerable concern regarding the ethical implications of such an approach. But using CRISPR to correct genetic mutations in the affected tissues of sick patients is not under debate.'

He added: 'These studies show a path where that is possible, but there is still a considerable amount of work to do.'

There is currently no effective treatment for DMD, which reduces life expectancy to about 30 years.

Robert Meadowcroft, Chief Executive of Muscular Dystrophy UK, said: 'It is vital that research using CRISPR technology continues to move forward. This kind of early-stage innovative research could being the next generation of therapies onto the horizon.'