Chen Benson S, Newman Nancy J
John van Geest Centre for Brain Repair and MRC Mitochondrial Biology Unit, Department of Clinical Neurosciences, University of Cambridge.
Cambridge Eye Unit, Addenbrooke's Hospital, Cambridge University Hospitals, Cambridge, UK.
Curr Opin Neurol. 2025 Feb 1;38(1):79-86. doi: 10.1097/WCO.0000000000001343. Epub 2024 Dec 20.
Leber hereditary optic neuropathy (LHON) is a mitochondrial DNA disease characterised by sequential bilateral vision loss due to loss of retinal ganglion cells. The purpose of this review is to provide an update on the results of recent clinical trials for LHON, focusing on studies of idebenone and lenadogene nolparvovec gene therapy.
Evidence from three clinical studies (RHODOS, RHODOS-OFU, and LEROS) suggest that idebenone should be started early and continued for at least 24 months. Treatment effect varies according to the stage of LHON and the underlying mutation. Favourable outcomes are associated with the m.11778G>A mutation and chronic eyes with the m.14484T>C mutation. Caution should be taken in subacute/dynamic eyes with the m.3460G>A mutation, due to possible clinical worsening with idebenone. Compared to eyes from an external natural history cohort, pooled data from four clinical studies (RESCUE, REVERSE, RESTORE and REFLECT) show that a single intravitreal injection of lenadogene nolparvovec can result in sustained bilateral visual improvement in m.11778G>A LHON patients aged ≥15 years when treated within 1 year of onset. Although the treatment effect is modest, the final visual acuity of treated patients (∼1.2 logMAR) significantly differs from the published natural history of LHON and the treatment benefit is more pronounced than the effect of idebenone alone in patients with the m.11778G>A mutation.
There is increasing evidence for the potential therapeutic benefit of idebenone and lenadogene nolparvovec gene therapy.
Leber遗传性视神经病变（LHON）是一种线粒体DNA疾病，其特征是由于视网膜神经节细胞丧失导致双侧视力逐渐丧失。本综述的目的是提供LHON近期临床试验结果的最新信息，重点关注艾地苯醌和利纳多吉奈韦克基因治疗的研究。
三项临床研究（RHODOS、RHODOS - OFU和LEROS）的证据表明，艾地苯醌应尽早开始使用，并持续至少24个月。治疗效果因LHON的阶段和潜在突变而异。有利的结果与m.11778G>A突变以及m.14484T>C突变的慢性眼病相关。对于m.3460G>A突变的亚急性/动态眼病，应谨慎使用艾地苯醌，因为使用后可能会导致临床症状恶化。与外部自然病史队列的眼睛相比，四项临床研究（RESCUE、REVERSE、RESTORE和REFLECT）的汇总数据显示，对于年龄≥15岁、发病1年内接受治疗的m.11778G>A LHON患者，单次玻璃体内注射利纳多吉奈韦克可导致双侧视力持续改善。尽管治疗效果不显著，但治疗患者的最终视力（约1.2 logMAR）与已发表的LHON自然病史有显著差异，且治疗益处比单独使用艾地苯醌对m.11778G>A突变患者的效果更明显。
越来越多的证据表明艾地苯醌和利纳多吉奈韦克基因治疗具有潜在的治疗益处。
