The results of a gene therapy trial on two children with Canavan disease, a rare, fatal, inherited metabolic brain disorder, show the transfer of a therapeutic gene can be successfully and safely introduced into the brain of young patients, with some positive effects. Researchers at Jefferson Medical College, who led the 1996 trial in New Zealand - a prelude to a larger study at Jefferson in 1998 and 1999 of 14 such patients - say the report bodes well for future use of gene therapy for brain diseases.
Canavan disease is a neurological disorder characterized by degeneration of the brain. It primarily affects children of Eastern European or Ashkenazi Jewish background. It is one of a group of genetic disorders called leukodystrophies that affect the growth of the myelin sheath of the nerve fibers in the brain. The myelin sheath is the fatty covering surrounding the nerve cells that acts as an insulator. The disease is caused by a genetic flaw in which an enzyme fails to be produced. Symptoms of Canavan disease, which appear in early infancy and progress quickly, may include mental retardation, loss or inability to acquire motor skills, difficulty feeding, loss of muscle tone, poor head control, and an abnormally enlarged head. Death comes within the first decade of life.
"This report presents the first gene transfer on two patients affected by a neurological disease," says Matthew During, M.D., professor of medicine at Jefferson Medical College and director of the CNS Gene Therapy Center at Thomas Jefferson University in Philadelphia.
Drs. During, Leone and their co-workers report the details of the trial in July in the Annals of Neurology. An editorial accompanies the report.
Canavan is caused by a defect in aspartocylase, or ASPA, an enzyme, which causes an over-production of a toxic compound in the brain, N-acetyl-aspartate (NAA).
"After the gene transfer, the patients had decreased NAA concentration in the brain followed by increased mye
Contact: Steve Benowitz
Thomas Jefferson University