Gene Therapy for Canavan Disease Safe and Effective
Reversed genetic defect and improved clinical status in 13 patients
THURSDAY, Dec. 20 (HealthDay News) -- In children with Canavan disease, a hereditary leukodystrophy that results in the degeneration of brain white matter caused by mutations in the aspartoacylase (ASPA) gene, gene therapy is safe, reverses the primary defect, and improves clinical status, according to a study published in the Dec. 19 issue of Science Translational Medicine.
Paola Leone, Ph.D., from the University of Medicine & Dentistry of New Jersey in Stratford, and colleagues treated 13 children with Canavan disease with an adeno-associated viral vector carrying the ASPA gene (AAV2-ASPA), via intraparenchymal delivery at six brain infusion sites.
Over at least five years of follow-up, the researchers found a decrease in elevated brain levels of N-acetyl-aspartate, the substrate of aspartoacylase that builds up in the absence of functional enzyme activity. There was also a relative stabilization of brain atrophy, reduced frequency of seizures, and stabilization of overall clinical status. There were no long-term adverse events related to the viral vector.
"Normalization of N-acetyl-aspartate at a very early age may be necessary to prevent irretrievable dysmyelination, motor delay, and mental retardation in Canavan disease," Leone and colleagues conclude. "Although AAV-ASPA delivered between 4 and 83 months appears to change the typical radiographical progression of disease, our data suggest that an earlier time window probably exists for effective treatment."
One author holds patents on AAV vector production and applications.