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Abstract：
BACKGROUND: Skeletal muscle ion channelopathies include non-dystrophic myotonias (NDM), periodic paralyses (PP), congenital myasthenic syndrome, and recently identified congenital myopathies. The treatment of these diseases is mainly symptomatic, aimed at reducing muscle excitability in NDM or modifying triggers of attacks in PP.
OBJECTIVE: This systematic review collected the evidences regarding effects of pharmacological treatment on muscle ion channelopathies, focusing on the possible link between treatments and genetic background.
METHODS: We searched databases for randomized clinical trials (RCT) and other human studies reporting pharmacological treatments. Preclinical studies were considered to gain further information regarding mutation-dependent drug effects. All steps were performed by two independent investigators, while two others critically reviewed the entire process.
RESULTS: For NMD, RCT showed therapeutic benefits of mexiletine and lamotrigine, while other human studies suggest some efficacy of various sodium channel blockers and of the carbonic anhydrase inhibitor (CAI) acetazolamide. Preclinical studies suggest that mutations may alter sensitivity of the channel to sodium channel blockers in vitro, which has been translated to humans in some cases. For hyperkalemic and hypokalemic PP, RCT showed efficacy of the CAI dichlorphenamide in preventing paralysis. However, hypokalemic PP patients carrying sodium channel mutations may have fewer benefits from CAI compared to those carrying calcium channel mutations. Few data are available for treatment of congenital myopathies.
CONCLUSIONS: These studies provided limited information about the response to treatments of individual mutations or groups of mutations. A major effort is needed to perform human studies for designing a mutation-driven precision medicine in muscle ion channelopathies.
OBJECTIVE: This systematic review collected the evidences regarding effects of pharmacological treatment on muscle ion channelopathies, focusing on the possible link between treatments and genetic background.
METHODS: We searched databases for randomized clinical trials (RCT) and other human studies reporting pharmacological treatments. Preclinical studies were considered to gain further information regarding mutation-dependent drug effects. All steps were performed by two independent investigators, while two others critically reviewed the entire process.
RESULTS: For NMD, RCT showed therapeutic benefits of mexiletine and lamotrigine, while other human studies suggest some efficacy of various sodium channel blockers and of the carbonic anhydrase inhibitor (CAI) acetazolamide. Preclinical studies suggest that mutations may alter sensitivity of the channel to sodium channel blockers in vitro, which has been translated to humans in some cases. For hyperkalemic and hypokalemic PP, RCT showed efficacy of the CAI dichlorphenamide in preventing paralysis. However, hypokalemic PP patients carrying sodium channel mutations may have fewer benefits from CAI compared to those carrying calcium channel mutations. Few data are available for treatment of congenital myopathies.
CONCLUSIONS: These studies provided limited information about the response to treatments of individual mutations or groups of mutations. A major effort is needed to perform human studies for designing a mutation-driven precision medicine in muscle ion channelopathies.
摘要：
背景：骨骼肌离子通道病包括非营养不良性肌痛（NDM），周期性麻痹(PP)，先天性肌无力综合征,最近发现了先天性肌病。这些疾病的治疗主要是对症治疗,旨在降低NDM中的肌肉兴奋性或改变PP发作的触发因素。
目的：本系统综述收集了有关药物治疗对肌肉离子通道病的影响的证据，关注治疗和遗传背景之间可能的联系。
方法：我们在数据库中搜索了随机临床试验（RCT）和报告药物治疗的其他人体研究。临床前研究被认为可以获得有关突变依赖性药物作用的进一步信息。所有步骤均由两名独立研究人员进行，而另外两个人批判性地审查了整个过程。
结果：对于NMD，RCT显示了美西律和拉莫三嗪的治疗益处，而其他人体研究表明各种钠通道阻滞剂和碳酸酐酶抑制剂（CAI）乙酰唑胺的某些功效。临床前研究表明，突变可能会在体外改变通道对钠通道阻滞剂的敏感性。在某些情况下已被翻译成人类。对于高钾血症和低钾血症PP，RCT显示CAI二氯苯甲酰胺预防瘫痪的功效。然而,与携带钙通道突变的患者相比,携带钠通道突变的低血钾PP患者从CAI获益较少.很少有数据可用于治疗先天性肌病。
结论：这些研究提供的关于单个突变或突变组治疗反应的信息有限。需要做出重大努力来进行人体研究，以设计一种突变驱动的肌肉离子通道病精准医学。
目的：本系统综述收集了有关药物治疗对肌肉离子通道病的影响的证据，关注治疗和遗传背景之间可能的联系。
方法：我们在数据库中搜索了随机临床试验（RCT）和报告药物治疗的其他人体研究。临床前研究被认为可以获得有关突变依赖性药物作用的进一步信息。所有步骤均由两名独立研究人员进行，而另外两个人批判性地审查了整个过程。
结果：对于NMD，RCT显示了美西律和拉莫三嗪的治疗益处，而其他人体研究表明各种钠通道阻滞剂和碳酸酐酶抑制剂（CAI）乙酰唑胺的某些功效。临床前研究表明，突变可能会在体外改变通道对钠通道阻滞剂的敏感性。在某些情况下已被翻译成人类。对于高钾血症和低钾血症PP，RCT显示CAI二氯苯甲酰胺预防瘫痪的功效。然而,与携带钙通道突变的患者相比,携带钠通道突变的低血钾PP患者从CAI获益较少.很少有数据可用于治疗先天性肌病。
结论：这些研究提供的关于单个突变或突变组治疗反应的信息有限。需要做出重大努力来进行人体研究，以设计一种突变驱动的肌肉离子通道病精准医学。
