Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.
GKT School of Medical Education, King's College London, London, UK.
J Neuromuscul Dis. 2021;8(3):383-400. doi: 10.3233/JND-200546.
Hereditary peripheral neuropathies are inherited disorders affecting the peripheral nervous system, including Charcot-Marie-Tooth disease, familial amyloid polyneuropathy and hereditary sensory and motor neuropathies. While the molecular basis of hereditary peripheral neuropathies has been extensively researched, interventional trials of pharmacological therapies are lacking.
We collated evidence for the effectiveness of pharmacological and gene-based treatments for hereditary peripheral neuropathies.
We searched several databases for randomised controlled trials (RCT), observational studies and case reports of therapies in hereditary peripheral neuropathies. Two investigators extracted and analysed the data independently, assessing study quality using the Oxford Centre for Evidence Based Medicine 2011 Levels of Evidence in conjunction with the Jadad scale.
Of the 2046 studies initially identified, 119 trials met our inclusion criteria, of which only 34 were carried over into our final analysis. Ascorbic acid was shown to have no therapeutic benefit in CMT1A, while a combination of baclofen, naltrexone and sorbitol (PXT3003) demonstrated some efficacy, but phase III data are incomplete. In TTR-related amyloid polyneuropathy tafamidis, patisiran, inotersen and revusiran showed significant benefit in high quality RCTs. Smaller studies showed the efficacy of L-serine for SPTLC1-related hereditary sensory neuropathy, riboflavin for Brown-Vialetto-Van Laere syndrome (SLC52A2/3) and phytanic acid-poor diet in Refsum disease (PHYH).
The 'treatable' variants highlighted in this project will be flagged in the treatabolome database to alert clinicians at the time of the diagnosis and enable timely treatment of patients with hereditary peripheral neuropathies.
遗传性周围神经病是一种影响周围神经系统的遗传性疾病，包括 Charcot-Marie-Tooth 病、家族性淀粉样多神经病和遗传性感觉运动神经病。虽然遗传性周围神经病的分子基础已经得到了广泛的研究，但缺乏药理学治疗的干预试验。
我们整理了遗传性周围神经病药物和基因治疗有效性的证据。
我们在几个数据库中搜索了遗传性周围神经病治疗的随机对照试验（RCT）、观察性研究和病例报告。两名调查员独立提取和分析数据，使用牛津循证医学中心 2011 年证据水平和 Jadad 量表评估研究质量。
在最初确定的 2046 项研究中，有 119 项试验符合我们的纳入标准，其中只有 34 项试验纳入了我们的最终分析。在 CMT1A 中，抗坏血酸没有治疗效果，而巴氯芬、纳曲酮和山梨醇（PXT3003）的联合治疗显示出一定的疗效，但 III 期数据不完整。在 TTR 相关淀粉样多神经病中，塔法米迪、帕西里斯兰、依诺特森和雷夫西南在高质量 RCT 中显示出显著的益处。较小的研究表明 L-丝氨酸对 SPTLC1 相关遗传性感觉神经病、核黄素对 Brown-Vialetto-Van Laere 综合征（SLC52A2/3）和植烷酸缺乏饮食对 Refsum 病（PHYH）的疗效。
本项目中强调的“可治疗”变异将在 treatabolome 数据库中标记，以便在诊断时提醒临床医生，并使遗传性周围神经病患者能够及时得到治疗。
