PDF(Pubmed)
Abstract：
Onasemnogene abeparvovec (OA) is the approved intravenous gene therapy for the treatment of spinal muscular atrophy (SMA). A functional copy of the human SMN1 gene was inserted into the target motor neuron cells via a viral vector, AAV9. In clinical trials, OA was infused through a peripheral venous catheter, and no data are available on central catheter use. Recently, we had a case where OA was administered directly into the right atrium via a peripherally inserted central catheter (PICC) instead of a peripheral line, as recommended. The patient was a female child aged 4 months, diagnosed as SMA type I. For practical reasons, a dose of OA according to the weight of the patient (1.1 × 1014 vectorial genomes/kg) was administered via PICC in 1 h, as the product information recommends. The drug was well tolerated, with no hypersensitivity reactions or initial elevation of transaminases or other adverse effects. To our knowledge, this is the first case reported where OA was administered via a central line. This type of administration is not contraindicated, but it is not specifically contemplated or recommended. It is unknown whether central line administration could have any implications for transduction efficiency and immunogenicity. Future studies should clarify these aspects, as each gene therapy has a specific optimal dose recorded that depends on the site and route of administration of the drug, the AAV variant and the transgene.
摘要：
Onasemnogeneabeparvovec（OA）是经批准的静脉内基因治疗，用于治疗脊髓性肌萎缩症（SMA）。通过病毒载体将人SMN1基因的功能拷贝插入到目标运动神经元细胞中，AAV9。在临床试验中,OA通过外周静脉导管输注,并且没有中心导管使用的数据。最近,我们有一个病例，OA通过外周中心静脉导管（PICC）而不是外周导管直接进入右心房，如推荐。病人是一名4个月大的女性儿童，诊断为SMAI型，出于实际原因，在1小时内通过PICC施用根据患者体重的OA剂量（1.1×1014矢量基因组/kg），根据产品信息推荐。该药耐受性良好，无超敏反应或转氨酶初始升高或其他不良反应。据我们所知,这是报告的第一例OA通过中央导管给药的病例.这种类型的管理不是禁忌的，但没有特别考虑或建议。尚不清楚中央线给药是否对转导效率和免疫原性有任何影响。未来的研究应该澄清这些方面，因为每种基因疗法都有一个特定的最佳剂量记录，这取决于药物的给药部位和途径，AAV变体和转基因。
