07 July 2004
ByAppeared in BioNews 266
Performing gene therapy on mice can prevent the symptoms of a hereditary brain disease called spinocerebellar ataxia (SCA). This discovery, made by a research team from the University of Iowa, US, has prompted hopes of similar treatments for related brain disorders such as Huntington's and Alzheimer's. Unlike other gene therapy techniques that add a new gene to replace a faulty one, this method uses genetic material to turn off an existing faulty gene. The research, originally reported at a conference in June, will appear in the journal Nature Medicine in August.
The researchers treated mice with symptoms of SCA, an autosomal dominant neurodegenerative disease similar to Huntington's disease (HD). Autosomal dominant diseases are caused by a single copy of a faulty gene, inherited from an affected parent. In both HD and SCA, the faulty gene is responsible for production of an abnormal protein, which causes neurological damage. The researchers used a technique called RNAi (RNA interference), to 'silence' the faulty SCA1 gene. This approach uses short pieces of RNA (a close chemical relative of DNA) to trigger an immune response specific to the targeted gene, preventing production of the faulty protein.
The research team used a modified virus to transfer the RNA to the mice brain cells and, after six months of treatment, found that the mice had normal movement and co-ordination. Untreated mice developed movement problems and the researchers found evidence of brain cells being destroyed. The study represents a step forward in several areas, including targeting specific brain cells by using a particular virus. Beverly Davidson, who led the research team described the research as 'the first example of targeted gene silencing of a disease gene in the brains of live animals' and she expressed hopes that 'this approach may eventually be useful for human therapies'.
Thomas Tuschl, who was involved in the discovery of the primitive immune system, said the findings were remarkable, but cautioned that although 'they can prevent the disease if they start the treatment early, before symptoms were apparent, they have not shown whether treating a diseased 10-week-old animal would improve the symptoms'. Other commentators have pointed out that treating Huntington's disease in the same manner would require targeting multiple areas of the brain.