合成药物疗法对隐性小脑性共济失调的重要性。

IF 3.4 2区 医学 Q2 CLINICAL NEUROLOGY Expert Review of Neurotherapeutics Pub Date : 2024-09-01 Epub Date: 2024-07-09 DOI:10.1080/14737175.2024.2376840
Marie Beaudin, Nicolas Dupre, Mario Manto
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引用次数: 0

摘要

导言:过去十年中,我们在确定遗传性共济失调症的新遗传原因、加深对疾病机制的了解以及开发治疗这些使人衰弱的疾病的疗法方面取得了重大突破:本文结合最常见的常染色体隐性遗传性共济失调症的已知发病机制,对目前已获批准和最有前景的候选药物疗法进行了综述。Omaveloxolone是一种Nrf2激活剂,可增强抗氧化防御能力,最近被批准用于治疗弗里德里希共济失调症。它的治疗效果并不明显,还需要进一步研究,以找到能阻止或逆转疾病进展的协同治疗方法。有希望的方法包括通过表观遗传机制上调 frataxin 的表达、直接蛋白替代和基因替代疗法。对于共济失调-特朗日病,有希望的方法包括剪接转换反义寡核苷酸和针对氧化应激、炎症和线粒体功能的小分子药物。此外,还回顾了已有疾病改变疗法的罕见隐性共济失调症,重点介绍了最近获批的疗法。还讨论了支持在隐性共济失调中使用利鲁唑和乙酰亮氨酸的证据:针对其他神经遗传病的基因疗法所取得的进展为实施可行的方法铺平了道路,这些方法可能会带来巨大的益处。特别是,当我们开发出针对这些疾病的有效治疗方法时,我们可能需要将各种疗法结合起来,考虑对新生儿进行症状前治疗检测,并优化非药物治疗方法。
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The importance of synthetic pharmacotherapy for recessive cerebellar ataxias.

Introduction: The last decade has witnessed major breakthroughs in identifying novel genetic causes of hereditary ataxias, deepening our understanding of disease mechanisms, and developing therapies for these debilitating disorders.

Areas covered: This article reviews the currently approved and most promising candidate pharmacotherapies in relation to the known disease mechanisms of the most prevalent autosomal recessive ataxias. Omaveloxolone is an Nrf2 activator that increases antioxidant defense and was recently approved for treatment of Friedreich ataxia. Its therapeutic effect is modest, and further research is needed to find synergistic treatments that would halt or reverse disease progression. Promising approaches include upregulation of frataxin expression by epigenetic mechanisms, direct protein replacement, and gene replacement therapy. For ataxia-telangiectasia, promising approaches include splice-switching antisense oligonucleotides and small molecules targeting oxidative stress, inflammation, and mitochondrial function. Rare recessive ataxias for which disease-modifying therapies exist are also reviewed, emphasizing recently approved therapies. Evidence supporting the use of riluzole and acetyl-leucine in recessive ataxias is discussed.

Expert opinion: Advances in genetic therapies for other neurogenetic conditions have paved the way to implement feasible approaches with potential dramatic benefits. Particularly, as we develop effective treatments for these conditions, we may need to combine therapies, consider newborn testing for pre-symptomatic treatment, and optimize non-pharmacological approaches.

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来源期刊
Expert Review of Neurotherapeutics
Expert Review of Neurotherapeutics Medicine-Neurology (clinical)
CiteScore
7.00
自引率
2.30%
发文量
61
审稿时长
4-8 weeks
期刊介绍: Expert Review of Neurotherapeutics (ISSN 1473-7175) provides expert reviews on the use of drugs and medicines in clinical neurology and neuropsychiatry. Coverage includes disease management, new medicines and drugs in neurology, therapeutic indications, diagnostics, medical treatment guidelines and neurological diseases such as stroke, epilepsy, Alzheimer''s and Parkinson''s. Comprehensive coverage in each review is complemented by the unique Expert Review format and includes the following sections: Expert Opinion - a personal view of the data presented in the article, a discussion on the developments that are likely to be important in the future, and the avenues of research likely to become exciting as further studies yield more detailed results Article Highlights – an executive summary of the author’s most critical points
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