Day John W, Finkel Richard S, Mercuri Eugenio, Swoboda Kathryn J, Menier Melissa, van Olden Rudolf, Tauscher-Wisniewski Sitra, Mendell Jerry R
Division of Neuromuscular Medicine, Stanford Neuroscience Health Center, MC 5979, 213 Quarry Road, Palo Alto, CA 94304, USA.
Center for Experimental Neurotherapeutics, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105, USA.
Mol Ther Methods Clin Dev. 2021 Feb 24;21:76-82. doi: 10.1016/j.omtm.2021.02.014. eCollection 2021 Jun 11.
Spinal muscular atrophy is a progressive, recessively inherited monogenic neurologic disease, the genetic root cause of which is the absence of a functional gene. Onasemnogene abeparvovec (formerly AVXS-101) is an adeno-associated virus serotype 9 vector-based gene therapy that delivers a fully functional copy of the human gene. We report anti-adeno-associated virus serotype 9 antibody titers for patients with spinal muscular atrophy when they were screened for eligibility in the onasemnogene abeparvovec clinical trials (intravenous and intrathecal administration) and managed access programs (intravenous). Through December 31, 2019, 196 patients and 155 biologic mothers were screened for anti-adeno-associated virus serotype 9 binding antibodies with an enzyme-linked immunosorbent assay. Of these, 15 patients (7.7%) and 23 biologic mothers (14.8%) had titers >1:50 on their initial screening tests. Eleven patients (5.6%) had elevated titers on their final screening tests. The low percentage of patients with exclusionary antibody titers indicates that most infants with spinal muscular atrophy type 1 should be able to receive onasemnogene abeparvovec. Retesting may identify patients whose antibody titers later decrease to below the threshold for treatment, and retesting should be considered for patients with anti-adeno-associated virus serotype 9 antibody titers >1:50.
脊髓性肌萎缩症是一种进行性、隐性遗传的单基因神经疾病，其基因根源是缺乏一个功能性基因。onasemnogene abeparvovec（原名AVXS - 101）是一种基于腺相关病毒9型载体的基因疗法，可提供人类基因的一个全功能拷贝。我们报告了脊髓性肌萎缩症患者在onasemnogene abeparvovec临床试验（静脉内和鞘内给药）及管理准入项目（静脉内给药）中进行资格筛查时的抗腺相关病毒9型抗体滴度。截至2019年12月31日，使用酶联免疫吸附测定法对196例患者和155名生物学母亲进行了抗腺相关病毒9型结合抗体筛查。其中，15例患者（7.7%）和23名生物学母亲（14.8%）在初次筛查试验中的滴度>1:50。11例患者（5.6%）在最终筛查试验中的滴度升高。具有排除性抗体滴度的患者比例较低，这表明大多数1型脊髓性肌萎缩症婴儿应该能够接受onasemnogene abeparvovec治疗。重新检测可能会识别出抗体滴度随后降至治疗阈值以下的患者，对于抗腺相关病毒9型抗体滴度>1:50的患者应考虑重新检测。
