Gene-editing injections could one day offer hope to those with the inherited disease Duchenne muscular dystrophy, research suggests.

Researchers were able to halt the progression of DMD in adult mice using a recently developed technique that has been hailed as the scientific breakthrough of 2015.



In a series of studies, three teams of US researchers showed how the gene-editing tool could be used to “correct” a mutation in the animals’ muscle DNA that prevented them producing the protein dystrophin, leading to partial recovery.



DMD is one of the most common and severe of a group of inherited muscle-wasting conditions that affect around 70,000 people in the UK, according to the charity Muscular Dystrophy UK. It is usually diagnosed in boys in early childhood, causing muscle degeneration, disability and premature death. Sufferers become increasingly immobile, and most can only expect to live to their 20s or 30s.



It is incurable, but the new research suggests that with gene-editing it might be possible to treat the condition simply by deleting a small piece of scrambled DNA whose presence prevents the gene working normally.

Although the treated mice were not completely cured, dystrophin gene activity was restored to a level that would be expected to achieve adequate muscle function in a patient with DMD.

The gene-editing tool, known as CRISPR-Cas9, is able to cut out a tiny piece of flawed DNA with surgical precision while avoiding complex and difficult traditional gene therapy. Crucially, it can be applied to adults and does not require controversial tampering with genes in eggs and sperm that are then passed on to future generations.



It harnesses a defence mechanism used against viruses to home in on targeted sections of DNA, which are then snipped away with an enzyme that acts like molecular “scissors”.



Only shown to work in human cells three years ago, the system has such enormous potential it was hailed as the 2015 breakthrough of the year by the journal Science.



The latest research, also published in Science, used a harmless virus injected to deliver the gene-editing components directly into the muscles of mice with DMD. This resulted in a small section of defective protein-coding DNA being “edited out”.

Natural repair mechanisms then stitched the two loose ends of the DNA molecule together to create a shortened but working version of the gene.



One study by scientists at Duke University found that the treatment restored dystrophin protein to roughly 8% of its normal level. Previous research has suggested that even 4% would be enough to achieve adequate muscle function in patients with DMD.



Dr Charles Gersbach, an associate professor of biomedical engineering at Duke University, 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. These studies show a path where that is possible, but there is still a considerable amount of work to do.”

Writing in Science, the authors say the approach could potentially be used to treat a range of neuromuscular disorders and many other diseases.

A second study led by scientists at Harvard University used a red fluorescent marker to show how the gene-editing treatment altered the development of muscle fibres.



The third study from the University of Texas demonstrated that the treatment worked best when the gene-editing kit was injected directly into muscles.

Rhonda Bassel-Duby, a professor of molecular biology at the University of Texas Southwestern medical centre and one of the authors said: “It’s a solid step toward a practical cure for DMD.”

Her colleague Eric Olson, the chairman of molecular biology and co-director of the university’s muscular dystrophy research centre, said: “This is different from other therapeutic approaches because it eliminates the cause of the disease. Importantly, in principle, the same strategy can be applied to numerous types of mutations within the human DMD patients.”

Before scientists can even think of clinical trials involving humans, there are a number of questions to settle, according to Robin Lovell-Badge of The Francis Crick Institute in London. One of these is the possibility of “off-target” events and unintended consequences that follow from such treatment.

“Such events may be of little or no consequence, but again without a detailed analysis this may worry regulators, and it is not clear that suitable methods to do this are yet available,” he said.

All three teams used a similar approach to remove a mutated length of DNA from the dystrophin gene. ”This leads to slightly smaller dystrophin protein with reduced activity than that present in normal mice, but any activity is considerably better than none,” he said.

He said the results were encouraging, but added that it was difficult to know whether the degree of restoration seen in the mice would be sufficient in humans. “However, it is thought that as little as 4% of normal dystrophin expression level is sufficient to improve muscle function and 30% protein expression may be sufficient for complete rescue,” he said.

































