Prevalence of Adeno-Associated Virus-9-Neutralizing Antibody in Chinese Patients with Duchenne Muscular Dystrophy

作者：Cuijie Wei, Dongliang Li, Meng Zhang, Yanping Zhao, Yidan Liu, Yanbin Fan, Lu Wang, Jieyu Liu, Xingzhi Chang, Yuwu Jiang, Hui Xiong · 发表于：Human Gene Therapy · 年份：2023 · DOI：10.1089/hum.2023.117 · 被引用次数：7 · 研究领域：Muscle Physiology and Disorders、Virus-based gene therapy research、CAR-T cell therapy research

The delivery of a mini-dystrophin gene to skeletal muscles using recombinant adeno-associated virus serotype (AAV) holds great potential as a gene therapy for Duchenne muscular dystrophy (DMD). However, the presence of anti-AAV-neutralizing antibodies (NAbs) may impede the effectiveness of gene transduction. This study aimed to evaluate the prevalence of anti-AAV9 NAbs in Chinese patients with DMD, and to characterize the target population for an AAV gene therapy. A total of one hundred male patients with DMD were included in this study, and demographic and clinical data were collected. A blood specimen was obtained from each participant for the purpose of evaluating the existence of anti-AAV9 NAbs through a cell-based functional assay conducted at a central laboratory. A NAb titer exceeding 1:4 was considered positive. The positivity rates of anti-AAV9 NAb were compared among different subgroups. The median age of this DMD cohort was 8 years old, ranging from 3 to 15 years of age. Forty-two percent of patients tested positive for anti-AAV9 NAb. Notably, all samples from patients under 4 years of age tested negative, and the positivity rates of anti-AAV9 NAb differed significantly across the three age subgroups (<4 years old, ≥4 years old and <12 years old, and ≥12 years old, χ 2 = 7.221, p = 0.023). Further investigation into the living environment revealed a higher positivity rate of anti-AAV9 NAb in rural patients compared with urban patients ( χ 2 = 3.923, p = 0.048...