R Rodríguez Laura, Lapeña Tamara, Calap-Quintana Pablo, Moltó María Dolores, Gonzalez-Cabo Pilar, Navarro Langa Juan Antonio
Department of Physiology, Faculty of Medicine and Dentistry. Universitat de València-INCLIVA, 46010 Valencia, Spain.
Associated Unit for Rare Diseases INCLIVA-CIPF, 46010, Valencia, Spain.
Antioxidants (Basel). 2020 Jul 24;9(8):664. doi: 10.3390/antiox9080664.
Friedreich´s ataxia is the commonest autosomal recessive ataxia among population of European descent. Despite the huge advances performed in the last decades, a cure still remains elusive. One of the most studied hallmarks of the disease is the increased production of oxidative stress markers in patients and models. This feature has been the motivation to develop treatments that aim to counteract such boost of free radicals and to enhance the production of antioxidant defenses. In this work, we present and critically review those "antioxidant" drugs that went beyond the disease´s models and were approved for its application in clinical trials. The evaluation of these trials highlights some crucial aspects of the FRDA research. On the one hand, the analysis contributes to elucidate whether oxidative stress plays a central role or whether it is only an epiphenomenon. On the other hand, it comments on some limitations in the current trials that complicate the analysis and interpretation of their outcome. We also include some suggestions that will be interesting to implement in future studies and clinical trials.
弗里德赖希共济失调是欧洲裔人群中最常见的常染色体隐性共济失调。尽管在过去几十年里取得了巨大进展，但仍然没有找到治愈方法。该疾病最受研究的特征之一是患者和模型中氧化应激标志物的产生增加。这一特征促使人们开发旨在抵消自由基增加并增强抗氧化防御能力的治疗方法。在这项工作中，我们展示并批判性地回顾了那些超越疾病模型并被批准用于临床试验的“抗氧化”药物。对这些试验的评估突出了弗里德赖希共济失调研究的一些关键方面。一方面，分析有助于阐明氧化应激是发挥核心作用还是仅仅是一种附带现象。另一方面，它评论了当前试验中的一些局限性，这些局限性使试验结果的分析和解释变得复杂。我们还提出了一些建议，这些建议在未来的研究和临床试验中实施会很有意义。
