Aix Marseille Univ, APHM, INSERM, Inst Neurosci Syst, University Hospital Federation DHUNE, Service de Pharmacologie Clinique et Pharmacovigilance, Marseille, France.
Aix Marseille Univ, CNRS, Inst Neurosci Timone, Marseille, France.
Expert Opin Investig Drugs. 2021 Jul;30(7):721-736. doi: 10.1080/13543784.2021.1928073. Epub 2021 May 31.
Mood disorders are severe yet frequent psychiatric disorders worldwide, comprising major depressive disorder (MDD) and bipolar disorders (BD). Their treatment remains poorly effective. Recently, growing evidence for epigenetic mechanisms has emerged. Consequently, a great interest in a novel pharmacological class arose: RNA therapeutics.
We conducted a systematic review of RNA therapeutics -antisense oligonucleotides (ASOs), small interfering RNAs (siRNAs), short hairpin RNAs (shRNAs), and micro-RNA (miRNA) therapeutics- for the treatment of mood disorders studied in pre-clinical animal models listed in PubMed, in clinical trials registered in ClinicalTrials.gov and available on the market by combining literature search and Food and Drug Administration and European Medicine Agency online databases. Eighteen pre-clinical studies investigated the antidepressant effects of RNA therapeutics. However, even though there is an increasing number of marketing authorizations and clinical trials for the past twenty years, no RNA therapeutic has reached the clinical development pipeline for the treatment of psychiatric disorders yet.
Several promising RNA therapeutics have been tested in pre-clinical studies for MDD, whereas no molecule has been developed for BD. There are several issues to address before reaching clinical development and new challenges include stratifying patient population and predicting therapeutic response.
心境障碍是全球范围内严重且常见的精神疾病，包括重性抑郁障碍（MDD）和双相情感障碍（BD）。其治疗效果仍然很差。最近，越来越多的证据表明存在表观遗传机制。因此，人们对一种新型的药理学药物产生了浓厚的兴趣：RNA 疗法。
我们在 PubMed 中对已发表的在临床前动物模型中研究用于治疗心境障碍的 RNA 疗法（反义寡核苷酸（ASO）、小干扰 RNA（siRNA）、短发夹 RNA（shRNA）和 microRNA 治疗）进行了系统评价，以及在 ClinicalTrials.gov 中注册的临床试验和市场上可获得的 RNA 疗法，通过结合文献检索和食品药品监督管理局和欧洲药品管理局在线数据库进行。有 18 项临床前研究调查了 RNA 疗法的抗抑郁作用。然而，尽管在过去二十年中，用于治疗精神疾病的 RNA 疗法的上市许可和临床试验数量不断增加，但尚无 RNA 疗法进入治疗精神障碍的临床开发管道。
有几种有前途的 RNA 疗法已在 MDD 的临床前研究中进行了测试，而尚无用于 BD 的分子。在进入临床开发之前，还有几个问题需要解决，新的挑战包括对患者人群进行分层和预测治疗反应。
