Groundbreaking 20-Year Study on Gene Therapy for CLN2 Disease Shows Promising Results Regarding Increased Survivorship of Patients

Researchers from the Department of Genetic Medicine recently published a study in Human Gene Therapy revealing significant findings from a 20-year survival analysis of gene therapy for CLN2 disease, a rare neurodegenerative disorder affecting the central nervous system and resulting in early death, typically at ages from 8-12 years. The study, led by Dr. Dolan Sondhi, Dr. Ronald G. Crystal, and colleagues, focused on the long-term effects of adeno-associated virus vector serotype 2 (AAV2) gene therapy that expresses the corrected CLN2 gene. The AAV2 therapy was developed by Department of Genetic Medicine researchers and administered to 10 children with CLN2 disease as part of a clinical trial initiated 20 years ago. The study found two distinct groups of patients with regard to survival: 7 of the 10 children demonstrated typical survival to a mean of about 9 years of age, while 3 of the 10 children showed significantly longer survival to a mean age of approximately 23 years. The reason for the difference in survival is unclear, with the genotypes of both groups predicted to be equally deleterious and suggesting that factors other than disease genetics alone may be contributing to the extended survival in a subset of the children treated with the gene therapy. Such factors may be that the three patients with longer survivals were older at the time of treatment and had larger brain ventricular volumes, possibly leading to greater distribution of the gene product. This study represents one of the longest survival analyses of AAV-treated individuals with hereditary disorders, highlighting the potential and variability of gene therapy efficacy.