一名有三个 SMN2 基因拷贝的无症状 SMA 患者的重复 AAV9 效价测定 - 病例报告。

IF 3.2 4区 医学 Q2 CLINICAL NEUROLOGY Journal of neuromuscular diseases Pub Date : 2024-01-01 DOI:10.3233/JND-221659
Astrid Eisenkölbl, Manuel Pühringer
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引用次数: 0

摘要

腺相关病毒(AAV)非常适合作为基因转移载体。Onasemnogene abeparvovec 使用 AAV9 作为病毒载体。然而,以前接触过野生型 AAV 或胎盘转移母体 AAV 抗体会引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。我们介绍了一例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。该婴儿在出生 9 天确诊时 AAV9 抗体滴度升高。由于确诊时无症状,因此决定每两周对患者的 AAV9 抗体滴度进行一次复查。初次诊断六周后,滴度为 1:12.5 的患者可以接受 onasemnogene abeparvovec 治疗。本病例表明,在 SMN2 基因拷贝数和无症状的条件下,onasemnogene abeparvovec 治疗最初被排除的 AAV9 抗体滴度大于 1:50 的患者是可行的。
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Repeated AAV9 Titer Determination in a Presymptomatic SMA Patient with Three SMN2 Gene Copies - A Case Report.

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.

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来源期刊
Journal of neuromuscular diseases
Journal of neuromuscular diseases Medicine-Neurology (clinical)
CiteScore
5.10
自引率
6.10%
发文量
102
期刊介绍: The Journal of Neuromuscular Diseases aims to facilitate progress in understanding the molecular genetics/correlates, pathogenesis, pharmacology, diagnosis and treatment of acquired and genetic neuromuscular diseases (including muscular dystrophy, myasthenia gravis, spinal muscular atrophy, neuropathies, myopathies, myotonias and myositis). The journal publishes research reports, reviews, short communications, letters-to-the-editor, and will consider research that has negative findings. The journal is dedicated to providing an open forum for original research in basic science, translational and clinical research that will improve our fundamental understanding and lead to effective treatments of neuromuscular diseases.
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