Research led by Paola Leone, PhD, of the University of Medicine and Dentistry of New Jersey-School of Osteopathic Medicine (UMDNJ-SOM), demonstrates the long term safety and benefit of a virus-based gene therapy that has been applied for the first time in a clinical setting. This novel therapy was used to treat young patients with Canavan disease, a devastating inherited neurological condition that typically takes a child's life by age ten. Results of the study have just been published in the journal Science Translational Medicine, in an article that describes this first clinical application of a viral-based gene therapy for a neurodegenerative/neurological disorder.
The symptoms of Canavan disease usually begin to appear by the time a child is six months old. Myelin, which in a healthy child coats nerves throughout the body, does not form properly within the brain. Over time, the brain then atrophies, typically causing symptoms that include severe cognitive and motor delay, epilepsy and ultimately death. The disease results from a defect in a single gene, giving researchers the hope that by targeting and replacing that gene in patients with the mutation, they might find a way to counteract the disease's effects.
The team led by Dr. Leone, who is an associate professor of cell biology at UMDNJ-SOM, implanted the ASPA gene (AAV2-ASPA) in 13 patients who were between three and 96 months of age, through use of an adeno-associated viral vector (9 x 10 to the 11th power vector genomes via intraparenchymal delivery at six brain diffusion sites). All members of the cohort were then followed for at least five years.
Adeno-associated viruses are nonpathogenic and can infect dividing and non-dividing cells (such as brain cells) and persist in an extrachromosomal state without integrating into the genome of the host cell, hence avoiding any endogenous oncogene activation. The researchers were able to adapt it in the laboratory to be an efficient delivery system for implantation of the human (healthy) ASPA gene without any possible wild-type virus contamination.