Sartorelli J, Ng J, Rahim A A, Waddington S N, Kurian M A
Developmental Neurosciences, Zayed Centre for Research Into Rare Disease in Children, UCL Great Ormond Street Institute of Child Health, 20 Guilford Street, London, WC1N 1DZ, UK.
Unit of Muscular and Neurodegenerative Diseases, Bambino Gesù Children's Hospital IRCCS, Rome, Italy.
J Neurol. 2025 Feb 22;272(3):220. doi: 10.1007/s00415-025-12940-5.
Movement disorders are a group of heterogeneous neurological conditions associated with alterations of tone, posture and voluntary movement. They may either occur in isolation or as part of a multisystemic condition. More recently, the advent of next generation sequencing technologies has facilitated better understanding of the underlying causative genes and molecular pathways, thereby identifying targets for genetic therapy. In this review, we summarize the advances in genetic therapy approaches for both hyperkinetic and hypokinetic movement disorders, including Parkinson's Disease, Huntington's Disease and rarer monogenic conditions of childhood onset. While there have been significant advances in the field, multiple challenges remain, related to safety, toxicity, efficacy and brain biodistribution, which will need to be addressed by the next generation of genetic therapies.
运动障碍是一组异质性神经系统疾病，与肌张力、姿势和自主运动的改变有关。它们既可能单独出现，也可能作为多系统疾病的一部分出现。最近，新一代测序技术的出现有助于更好地理解潜在的致病基因和分子途径，从而确定基因治疗的靶点。在这篇综述中，我们总结了针对多动性和少动性运动障碍的基因治疗方法的进展，包括帕金森病、亨廷顿舞蹈症以及儿童期发病的罕见单基因疾病。虽然该领域已经取得了重大进展，但仍存在多个挑战，涉及安全性、毒性、疗效和脑内生物分布等方面，这些都需要新一代基因治疗来解决。
