PDF(Pubmed)
Abstract：
Adeno-associated viruses (AAV) are well-suited to serve as gene transfer vectors. Onasemnogene abeparvovec uses AAV9 as virus vector. Previous exposure to wild-type AAVs or placental transfer of maternal AAV antibodies, however, can trigger an immune response to the vector virus which may limit the therapeutic effectiveness of gene transfer and impact safety. We present the case of a female patient with spinal muscular atrophy (SMA) and three survival motor neuron 2 (SMN2) gene copies. The infant had elevated titers of AAV9 antibodies at diagnosis at 9 days of age. Being presymptomatic at diagnosis, it was decided to retest the patient\'s AAV9 antibody titer at two-weekly intervals. Six weeks after initial diagnosis, a titer of 1:12.5 allowed treatment with onasemnogene abeparvovec. The presented case demonstrates that, provided the number of SMN2 gene copies and the absence of symptoms allow, onasemnogene abeparvovec therapy is feasible in patients with initially exclusionary AAV9 antibody titers of >1:50.
摘要：
腺相关病毒(AAV)非常适合用作基因转移载体。Onasemnogeneabeparvovec使用AAV9作为病毒载体。以前接触野生型AAV或母体AAV抗体的胎盘转移，然而,可以触发对载体病毒的免疫反应，这可能会限制基因转移的治疗效果并影响安全性。我们介绍了一名患有脊髓性肌萎缩症（SMA）和三个存活运动神经元2（SMN2）基因拷贝的女性患者的病例。婴儿在9日龄诊断时具有升高的AAV9抗体滴度。在诊断时出现症状，我们决定每隔两周重新测试患者的AAV9抗体滴度.初步诊断后六周,滴度为1:12.5，允许用asemnogeneabeparvovec治疗。提出的案例表明，如果SMN2基因拷贝数和没有症状允许，在最初排除性AAV9抗体滴度>1:50的患者中，无基因abeparvovec治疗是可行的。
