Gene therapy helps Lou Gehrig's disease

The most common form of motor neurone disease, called amyotrophic lateral sclerosis (ALS) or Lou Gehrig's disease, is caused when neurones in the spinal cord die, leading to muscle wasting and total paralysis.

Two separate teams of researchers from the UK and Switzerland used a gene therapy approach to interfere with the faulty SOD1 gene in mice. Interfering with faulty genes may slow down the progression of motor neurone disease.

Tests suggest that the technique of RNA interference, while not a cure, can slow this fatal nerve wasting illness.

About 10% of cases are inherited, caused by at least 100 different mutations in a protein known as SOD1. Mice, genetically engineered to carry this faulty human gene, developed a disease that looks like human ALS. Each team was able to show that they could delay the disease's effects and help their genetically engineered mice live longer. Different lentiviruses, long-lived viruses related to HIV that are good at delivering genetic material to cells were used by the two the teams. The researchers disabled the viruses, then they genetically engineered them to carry a specific sequence of the genetic material RNA. This interferes with the faulty RNA that the mutant human SOD1 genes in the mice produce.

By using lentiviruses to silence the mutant genes considerable therapeutic benefit was provided by delaying onset and prolonging the duration of motor neurone disease, said Professor Patrick Aebischer of the Swiss Federal Institute of Technology in Lausanne, Switzerland.

The UK team injected its gene therapy into the spines and various muscles of the ALS mutant mice and when Dr Mimoun Azzouz of Oxford Biomedica and colleagues dissected the mice, they found the treated mice had more healthy motor neurones than untreated mice.

It took twice as long as normal for ALS symptoms to start and the mice lived for 80% of their normal lifespan.