Ogbonmide Tolu, Rathore Rajni, Rangrej Shahid B, Hutchinson Stedrea, Lewis Marcia, Ojilere Stephenie, Carvalho Victoria, Kelly Irenaissia
College of Medicine, Saint James School of Medicine, Saint Vincent and Grenadines, VCT.
Pharmacology and Therapeutics, Saint James School of Medicine, Saint Vincent and grenadines, VCT.
Cureus. 2023 Mar 15;15(3):e36197. doi: 10.7759/cureus.36197. eCollection 2023 Mar.
Spinal Muscular Atrophy (SMA) is a genetic disease that causes weakness and wasting in the voluntary muscles of infants and children. SMA has been the leading inherited cause of infant death. More specifically, SMA is caused by the absence of the SMN1 gene. In May 2019, the Food and Drug Administration (FDA) approved onasemnogene abeparvovec, SMN1 gene replacement therapy, for all children with SMA younger than two years of age, without end-stage weakness. The objective of the study is to review the safety and efficacy of a novel gene therapy, onasemnogene abeparvovec (Zolgensma), for SMA and assess current challenges for gene therapy. For this, we have conducted a literature search on PubMed, MEDLINE, and Ovid (2019 to 2022) in the English language using the terms SMA, onasemnogene, and gene therapy. The search included articles, websites, and published papers from reputable health organizations, hospitals, and global organizations dedicated to bringing awareness to Spinal Muscular Atrophy. We found the first gene therapy for SMA to be onasemnogene, directly providing the survival motor neuron 1 (SMN1) gene to produce the survival motor neuron (SMN) protein. Onasemnogene is approved by the Food and Drug Administration and has the added benefit of being a one-time dose. On the downside, a major side effect of this treatment is hepatotoxicity. There is substantial evidence that the efficacy of therapy is increased when administered early to children under three months of age. Therefore, we concluded that onasemnogene appears to be an efficacious therapy for younger pediatric patients with SMA type 1. Drug cost and potential hepatotoxicity are major concerns. Long-term benefits and risks have not been determined, but it is more cost-effective and requires less time of treatment compared to the other used drug, nusinersen. Therefore, the combined safety, cost, and effectiveness of onasemnogene abeparvovec make it a reliable treatment option for treating SMA Type 1.
脊髓性肌萎缩症（SMA）是一种遗传性疾病，会导致婴幼儿和儿童的随意肌出现无力和萎缩。SMA一直是婴儿死亡的主要遗传性病因。更具体地说，SMA是由SMN1基因缺失引起的。2019年5月，美国食品药品监督管理局（FDA）批准了onasemnogene abeparvovec（一种SMN1基因替代疗法）用于治疗所有年龄小于两岁且无终末期肌无力的SMA患儿。本研究的目的是评估一种新型基因疗法onasemnogene abeparvovec（Zolgensma）治疗SMA的安全性和有效性，并评估基因疗法当前面临的挑战。为此，我们使用“SMA”“onasemnogene”和“基因疗法”等术语在PubMed、MEDLINE和Ovid数据库（2019年至2022年）中进行了英文文献检索。检索范围包括文章、网站以及来自知名健康组织、医院和致力于提高脊髓性肌萎缩症认知度的全球组织发表的论文。我们发现第一种用于治疗SMA的基因疗法是onasemnogene，它直接提供生存运动神经元1（SMN1）基因以产生生存运动神经元（SMN）蛋白。Onasemnogene已获美国食品药品监督管理局批准，并且具有一次性给药的优势。不利的一面是，这种治疗的一个主要副作用是肝毒性。有大量证据表明，在三个月龄以下儿童中早期给药时，治疗效果会增强。因此，我们得出结论，onasemnogene似乎是治疗1型SMA的年幼儿童患者的一种有效疗法。药物成本和潜在的肝毒性是主要关注点。长期的益处和风险尚未确定，但与另一种使用的药物nusinersen相比，它更具成本效益且治疗所需时间更少。因此，onasemnogene abeparvovec在安全性、成本和有效性方面的综合表现使其成为治疗1型SMA的可靠治疗选择。
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