Section of Pharmacology, Department of Precision and Regenerative Medicine, School of Medicine, University of Bari Aldo Moro, Piazza Giulo Cesare, 70124, Bari, Italy.
Section of Pharmacology, Department of Precision and Regenerative Medicine, School of Medicine, University of Bari Aldo Moro, Piazza Giulo Cesare, 70124, Bari, Italy.
Curr Opin Pharmacol. 2023 Feb;68:102329. doi: 10.1016/j.coph.2022.102329. Epub 2022 Dec 10.
Skeletal muscle ion channelopathies are rare genetic diseases mainly characterized by myotonia (muscle stiffness) or periodic paralysis (muscle weakness). Here, we reviewed the available therapeutic options in non-dystrophic myotonias (NDM) and periodic paralyses (PP), which consists essentially in drug repositioning to address stiffness or weakness attacks. Empirical use followed by successful randomized clinical trials eventually led to the orphan drug designation and marketing authorization granting of mexiletine for NDM and dichlorphenamide for PP. Yet, these treatments neither consider the genetic cause of the diseases nor address the individual variability in drug response. Thus, ongoing research aims at the identification of repurposed drugs alternative to mexiletine and dichlorphenamide to allow personalization of treatment. This review highlights how drug repurposing may represent an efficient strategy in rare diseases, allowing reduction of drug development time and costs in a context in which the return on investment may be particularly challenging.
骨骼肌离子通道病是一种罕见的遗传性疾病，主要表现为肌强直（肌肉僵硬）或周期性瘫痪（肌肉无力）。在这里，我们回顾了非营养不良性肌强直症（NDM）和周期性瘫痪（PP）的现有治疗选择，这些选择主要包括重新定位药物以治疗僵硬或无力发作。经验性使用后成功的随机临床试验最终导致美西律被指定为治疗 NDM 的孤儿药，并获得了氯苯酰胺治疗 PP 的上市许可。然而，这些治疗方法既不考虑疾病的遗传原因，也不考虑药物反应的个体差异。因此，目前的研究旨在寻找替代美西律和氯苯酰胺的重新定位药物，以实现治疗的个体化。这篇综述强调了药物再利用如何在罕见疾病中代表一种有效的策略，允许在投资回报可能特别具有挑战性的情况下缩短药物开发时间和降低成本。
