Many individuals with Niemann-Pick disease lack neutralizing antibodies against AAV2 or AAV9

A new study in the peer-reviewed journal Human Gene Therapy showed that more than half of individuals with Niemann-Pick disease, type C1 (NPC1) who were tested lacked neutralizing antibodies against either adeno-associated virus (AAV) 2 or AAV9. 

NPC1 is a rare, fatal neurodegenerative disorder, for which systemic AAV9-based gene therapy in mouse models has shown some success. The presence of neutralizing antibodies against AAV can reduce or negate the benefit of gene therapy.

Forbes Porter, from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, and coauthors assessed the prevalence of anti-AAV9 and anti-AAV2 neutralizing antibodies (NAbs) in serum samples from individuals with NPC1 at two different time points: around the time of diagnosis (0.9–17 years old) and between 4–15 years later (6–28 years old). The investigators found that more than half of patients were seropositive at both time points, with 68.2% of individuals lacking antibodies against AAV2 at both timepoints and 59.1% and 63.6% lacking antibodies to AAV9 at the first and second time points, respectively.

"These data support the feasibility of systemic or direct central nervous system AAV9 therapy in this patient population," concluded the investigators.

Studies like these are very important to plan delivery strategies for gene therapy treatments in general and for NPC1 patients specifically, such as determining enrollment criteria for trials, whether the treatment protocol needs to mitigate pre-existing NAbs, and the possibility that the development of NAbs during the course of life could impact the durability of treatment."

Thomas Gallagher, PhD, Managing Editor of Human Gene Therapy, University of Massachusetts Chan Medical School