Molecular scalpel hope for Duchenne muscular dystrophy

 

Muscle fibres (purple) are replaced by fat (black) in muscular dystrophy.

A 'molecular scalpel' shows promise in patients with a deadly muscle wasting condition, according to researchers.

The gene for the protein dystrophin is damaged in people with Duchenne muscular dystrophy.
A drug trial on 19 children, published in the Lancet, used the 'scalpel' to removed the damage and restore dystrophin production.
The charity Muscular Dystrophy Campaign said there was "real hope for the future".
Duchenne muscular dystrophy affects one in every 3,500 newborn boys.
Throughout life the muscle wastes away and children can need a wheelchair by the age of 10. The condition can become life-threatening before the age of 30, when it affects the muscles needed to breathe and pump blood around the body.
New approach The instructions for making a protein are in the genetic code, but this can be disrupted by mutations or deletions in the code.
Stem cell and gene therapy research has tried to find ways of introducing a functional dystrophin gene.
This study tried to do the best it could with the damaged code.

Muscular dystrophy

• Muscular dystrophies are a group of more than 20 different genetic neuromuscular disorders
• The most common, Duchenne muscular dystrophy (DMD), affects about one in 3,500 boys
• About 100 boys are born with the condition in the UK each year.
• Duchenne muscular dystrophy is caused by problems in a gene on the X chromosome that makes a protein called dystrophin, found in muscle fibres
• Muscle fibres break down and are gradually lost
• Another form - Becker muscular dystrophy - has similar but milder symptoms

The researchers at the Institute of Child Health at University College London injected tailored pieces of antisense RNA - the scalpel.

This removed a piece of the genetic code allowing it to be matched up either side of the mutation.
The result is a shorter, but still functional, dystrophin.
In the trial, seven out of the 19 children had some degree of dystrophin production restored - all of them were receiving the highest doses.
Professor Francesco Muntoni, lead researcher, told the BBC: "The best result was 20% of normal dystrophin levels. That is quite remarkable considering the study was for 12 weeks.
"I've worked with patients with Duchenne muscular dystrophy for many years and this is the first time we can say with confidence that we've made a significant breakthrough towards finding a targeted treatment."
However, he said that as the scalpel was tailored to a specific mutation it could not benefit everyone, in this case around 13% of patients.

"The second most common mutation affects 11% - which needs another scalpel."
Dr Marita Pohlschmidt, director of the Muscular Dystrophy Campaign, said the study was "quite a big deal".
"If we can change severe symptoms in Duchenne into something milder, that would be fantastic.
"We have fought to find a treatment for this devastating condition for the past 50 years. Today we can say with real confidence that we're going to win that battle. Parents of these boys can have real hope for the future."