Scientists target rogue RNAs to correct muscular dystrophy in mice

US scientists have used a new technique to treat a type of muscular dystrophy in mice. The new method, published in the journal Science, targets the genetic mechanism underlying the disease and was found to improve muscle function and reverse the long term degenerative effects of the condition.

Muscular dystrophy is a genetic disorder that causes progressive muscle wasting and weakness. Myotonic dystrophy, the most common type of muscular dystrophy, is characterised by prolonged muscle tensing and an inability to relax certain muscles after use. It is often worst in the hands, which can become locked in a grip. The genetic cause of myotonic dystrophy has been known since 1992, but there are currently no treatments for the disease.

The genetic mutation that causes myotonic dystrophy is unusual because instead of causing a defect in a protein needed for muscle function, it causes a defect in the mRNA (messenger RNA) of sufferers. mRNA is a molecule that acts as a translator, relaying the information encoded in a cell's DNA to the proteins that make up the cell and affect the cell's function. In myotonic dystrophy, a toxic mRNA is formed that binds to proteins and holds them in the nucleus of the cell, preventing them from carrying out their normal function.

In the new study, from the University of Rochester Medical Center in Rochester, New York, the researchers created a synthetic molecule, called an antisense morphilino oligonucleotide, that binds specifically to the toxic mRNA and neutralises it, releasing the proteins that are being held captive. When they injected this molecule into the muscles of mice that had been genetically engineered to mimic the effects of myotonic dystrophy, they observed the release of a key protein called muscleblind like-1, which is important to the control of muscle cell activity. This restored normal muscle cell control and led to improved muscle function.

Dr Charles Thornton, who led the research team, explained: ‘All the bricks and mortar for building a healthy body are there; some of them are just in the wrong place and can't do their job'. He added: ‘We don't have to replace a bad gene. All we have to do is to keep this toxic RNA and these proteins from sticking to one another'.

The researchers hope that one day this technique may be used in humans to combat, or even cure, myotonic dystrophy, although there is much more work to be done first. In particular, as myotonic dystrophy affects muscles and organs throughout the body, a method of delivering the molecule to the whole body rather than just one muscle would need to be developed. Dr Thornton said: ‘this study establishes a proof of concept that could be followed to develop a successful treatment for myotonic dystrophy'.