Gene-swap therapy eases rare brain disease

A new therapy that uses a virus to switch genes in the brain may help extend the lives of children with a rare and fatal neurodegenerative disorder. The results of the clinical trial, which began in 2001, show that the gene therapy cocktail conveyed into the brain by a molecular special delivery vehicle holds promise for children with Canavan disease.

As reported in Science Translational Medicine, the treatment uses a virus (adeno-associated virus, or AAV) as a “viral vector” meticulously tailored to enter the brain and safely switch good genes for bad.

“This was the first AAV-based gene therapy produced by a US academic institution to be approved for neurological use by the FDA,” says R. Jude Samulski, professor of pharmacology and director of the University of North Carolina Gene Therapy Center.

“It’s also the first vector produced by the university’s Gene Therapy Center Vector Core facility to go into patients.”

Children with Canavan disease have mutations in the ASPA gene that normally codes for an enzyme that helps the brain degrade N-acetyl-aspartate (NAA). The unregulated buildup of NAA is toxic to the brain’s gray matter, the protective myelin sheath surrounding nerve cells.

As the myelin deteriorates and neurons become unable to communicate, the child’s head size increases (macrocephaly), there are problems with movement, such as an inability to crawl, seizures occur, vision becomes impaired, and the children often die by age three. Fewer than 1,000 children in the US have the disorder.