Günther René
Klinik und Poliklinik für Neurologie, University Hospital Carl Gustav Carus at Technische Universität Dresden, Dresden, Germany.
Fortschr Neurol Psychiatr. 2023 Apr;91(4):153-163. doi: 10.1055/a-2002-5215. Epub 2023 Feb 23.
In the past, the diagnosis of motor neuron diseases such as amyotrophic lateral sclerosis (ALS) and 5q-associated spinal muscular atrophy (SMA) meant powerlessness in the face of seemingly untreatable diseases with severe motor-functional limitations and sometimes fatal courses. Recent advances in an understanding of the genetic causalities of these diseases, combined with success in the development of targeted gene therapy strategies, spell hope for effective, innovative therapeutic approaches, pioneering the ability to treat neurodegenerative diseases. While gene therapies have been approved for SMA since a few years, gene therapy research in ALS is still in clinical trials with encouraging results. This article provides an overview of the genetic background of ALS and SMA known to date and gene therapy approaches to them with a focus on therapy candidates that are in clinical trials or have already gained market approval.
过去,诸如肌萎缩侧索硬化症(ALS)和5q相关脊髓性肌萎缩症(SMA)等运动神经元疾病的诊断意味着面对看似无法治疗的疾病时无能为力,这些疾病存在严重的运动功能限制,有时病程还会致命。对这些疾病遗传病因认识的最新进展,再加上靶向基因治疗策略开发的成功,为有效、创新的治疗方法带来了希望,开创了治疗神经退行性疾病的能力。虽然基因疗法几年前就已获批用于治疗SMA,但ALS的基因治疗研究仍处于临床试验阶段,结果令人鼓舞。本文概述了迄今为止已知的ALS和SMA的遗传背景以及针对它们的基因治疗方法,重点关注正在进行临床试验或已获得市场批准的治疗候选药物。