Genetic therapy hope for muscle weakness disease

Boosting the activity of a gene could help treat people with an inherited muscle weakness disease, German researchers say. They have used a drug to help increase the levels of a crucial nerve protein missing in patients with spinal muscular atrophy (SMA). The team, based at the University of Cologne, say that treatment - a drug currently used to treat epilepsy, called valproate - may lead to a better quality of life for SMA patients. Team leader Brunhilde Wirth reported the findings at the recent annual conference of the European Society of Human Genetics in Amsterdam.

SMA is a relatively common genetic condition that affects around one in every 6000 babies born. It affects motor neurons - the nerve cells that control voluntary muscles used for movement. In people with SMA, the motor neurons are lacking a protein called SMN, so the cells gradually die off, causing progressive weakness in the muscles of the legs, arms and trunk. The disease affects people who inherit two faulty versions of a gene that makes SMN (called SMN1) - one from each parent. There is another gene that makes SMN, called SMN2, although it is usually only responsible for making around ten per cent of the protein.

In the latest study, the researchers wanted to find out if they could treat the symptoms of SMA by 'ramping up' SMN2 gene activity, to compensate for the faulty SMN1 gene. They found that treating cells grown in the laboratory with valproate increased production of the SMN protein between two and four times. The team then carried out a pilot trial involving ten parents of SMA patients, and found that the drug 'significantly' increased blood levels of SMN. Twenty SMA patients were then treated with valproate by their doctors, seven of whom showed an increase in SMN production.

Professor Wirth says the findings need to be followed up with more extensive trials, to find out if the increased levels of SMN protein in the blood are reflected in the patients' motor neurons. 'Unfortunately there is very little interest from the pharmaceutical industry in clinical trials for rare disorders', she said, adding 'however, the long-term outcome could be both improved therapy to enable a better quality of life for SMA patients, and also the introduction of neonatal screening so that therapy could be started before the first symptoms appear'.

Speaking on behalf of the British Society of Human Genetics, Dr Fred Kavalier said that 'this work shows it may be possible to influence the behaviour of genes with drugs'. He told BBC News Online that 'this is not a cure for SMA, but it's a small step along the road that may lead to effective treatment'.

In another presentation made at the conference, a group based at Leiden University Medical Centre in the Netherlands reported that valproate might also help treat patients with another genetic condition, called X-linked adrenoleukodystrophy. The scientists say they hope to begin a clinical trial to test the drug's effectiveness, in collaboration with French researchers based at the Hospital Saint Vincent de Paul in Paris.