Pre-existing immunity against adeno-associated viruses (AAVs), which are naturally very widespread, is one of the obstacles to gene therapy using such a vector. Zolgensma (onasemnogene abeparvovec), a gene therapy authorized in SMA, is in particular composed of an AAV9. When setting up clinical trials with Zolgensma, young participants whose anti-AAV9 antibody level exceeded 1:50 were thus excluded because of the risk on the safety and efficacy of the gene therapy product. But how many children are affected?
A study conducted by the team of J. Mendell (Columbus, United States) has just revealed a lower level of anti-AAV9 antibodies than expected. By analyzing the samples of 196 young patients under 5 years of age with SMA who received Zolgensma in a clinical trial or in early access as well as those of 155 mothers of affected children, likely to transmit anti-AAV9 antibodies to their babies during pregnancy, she showed that:
- 7.7% of young patients have an anti-AAV9 level greater than 1:50,
- among the 12 children who had a high rate and who were retested, four had a rate that was ultimately less than 1:50, suggesting that it may decrease before the age of 4 months,
- 14.8% of mothers have an anti-AAV9 level greater than 1:50.
Most young patients should therefore be able to receive Zolgensma.
