脊髓性肌萎缩症(SMA):治疗策略、挑战和未来前景

Nikunja Kishor Mishra, Amiyakanta Mishra
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引用次数: 0

摘要

脊髓性肌萎缩症(SMA)是一种小儿神经肌肉疾病,以存活运动神经元1 (SMN1)基因的缺陷或突变为特征。这是一种影响深远的儿童运动神经元疾病。在最严重的情况下,在没有治疗的情况下,它悲惨地导致在生命的最初两年内死亡。该病以肌肉无力和萎缩为特征,主要发生在肢体近端肌肉。导致SMA最常见的突变是SMN1外显子7的纯合缺失。最近的治疗突破通过使用基因治疗或替代基因操作技术解决SMN蛋白的缺陷,为家庭和患者提供了希望。越来越清楚的是,这些治疗方法都不能单独治愈SMA。因此,本研究的目的是回顾组织中SMN蛋白水平与SMA病理之间的关系。它还旨在对目前获得许可的三种SMA疗法进行全面审查,简要概述其临床前和临床研究,并结合实际数据分析。此外,该研究还深入讨论了联合治疗、补充治疗方法、临床护理中的挑战以及SMA治疗的未来前景。材料和方法本研究的数据收集自一系列学术来源,包括PubMed、Scopus、b施普林格和其他相关搜索引擎。选择这些来源是为了确保获得关于SMA管理的最新和最全面的文献,反映了当前的治疗范例和该领域的进展。结果利斯迪普兰、阿伯帕韦克和nusinersen的临床前和临床研究表明,SMN蛋白的功能恢复及其在外周组织和中枢神经系统(CNS)运动神经元中的分布,代表了治疗SMA的前景。临床试验和实际数据为现有药物的有效性和安全性提供了强有力的支持。nusinersen、onasemnogene abeparvovec和risdiplam这三种疗法旨在提高SMA患者的SMN水平。目前,在联合治疗中已经观察到安全性、有效性和运动功能的改善,例如TOPAZ研究(Nusinersen与Aptiegromab)、RESPOND研究(Nusinersen与Onasemnogene abeparvovec)和SAPPHIRE研究(Aptiegromab与Nusinersen或risdiplam)。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Spinal Muscular Atrophy (SMA): Treatment strategies, challenges and future prospects

Introduction

Spinal muscular atrophy (SMA) is a pediatric neuromuscular disorder that is distinguished by a defect or mutation in the survival motor neuron1 (SMN1) gene. It is a profoundly impactful childhood motor neuron disorder. In its most severe instances and in the absence of treatment, it tragically results in death within the initial two years of life. The disease is identified by muscle weakness and atrophy, predominating in proximal limb muscles. The most common mutation causing SMA is a homozygous deletion of exon 7 of SMN1. Recent therapeutic breakthroughs provide hope to families and patients by tackling the deficiency in SMN protein using gene therapy or alternative genetic manipulation techniques. It is becoming increasingly clear that none of these therapies alone will provide a cure for SMA. Therefore, the objective of the study is to review the correlation between SMN protein levels in tissues and the pathology of SMA. It also aims to provide a comprehensive review of the three currently licensed therapies for SMA, offering a brief overview of their preclinical and clinical studies that led to marketing authorization, coupled with real-world data analysis. Additionally, the study delves into discussions surrounding combined therapy, supplementary therapeutic approaches, challenges in clinical care, and future prospects for the treatment of SMA.

Materials and methods

The data for this study were gathered from a range of scholarly sources, including PubMed, Scopus, Springer and other relevant search engines. These sources were selected to ensure access to the latest and most comprehensive literature on SMA management, reflecting current treatment paradigms and advancements in the field.

Results

Both preclinical and clinical investigations of risdiplam, onasemnogene abeparvovec, and nusinersen have elucidated the restoration of functional SMN protein and its distribution in both peripheral tissues and central nervous system (CNS) motor neurons, representing a promising therapeutic benefit for the treatment of SMA.

Discussion

Clinical trials and real-world data provide robust support for the efficacy and safety profiles of the available drugs. Three therapies, nusinersen, onasemnogene abeparvovec, and risdiplam, aim to increase SMN levels in patients with SMA. Currently, an improvements in safety, efficacy, and motor function have been observed in combination therapies, such as the TOPAZ study (Nusinersen with Aptiegromab), the RESPOND study (Nusinersen with Onasemnogene abeparvovec) and the SAPPHIRE study (Aptiegromab alongside nusinersen or risdiplam).
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