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他汀类药物多效性在神经退行性疾病中的重新利用的前瞻性见解:一项解释性评估。

Perspective insights of repurposing the pleiotropic efficacy of statins in neurodegenerative disorders: An expository appraisal.

作者信息

Bhat Aditi, Dalvi Harshita, Jain Harsha, Rangaraj Nagarjun, Singh Shashi Bala, Srivastava Saurabh

机构信息

Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, Telangana, 500037, India.

Department of Pharmacology and Regulatory Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, Telangana, 500037, India.

出版信息

Curr Res Pharmacol Drug Discov. 2020 Dec 31;2:100012. doi: 10.1016/j.crphar.2020.100012. eCollection 2021.

Abstract

Neurodegenerative disorders which affects a larger population pose a great clinical challenge. These disorders impact the quality of life of an individual by damaging the neurons, which are the unit cells of the brain. Clinicians are faced with the grave challenge of inhibiting the progression of these diseases as available treatment options fail to meet the clinical demand. Thus, treating the disease/disorder symptomatically is the Hobson's choice. The goal of the researchers is to introduce newer therapies in this segment and introducing a new molecule will take long years of development. Hence, drug repurposing/repositioning can be a better substitute in comparison to time consuming and expensive drug discovery and development cycle. Presently, a paradigm shift towards the re-purposing of drugs can be witnessed. Statins which have been previously approved as anti-hyperlipidemic agents are in the limelight of research for re-purposed drugs. Owing to their anti-inflammatory and antioxidant nature, statins act as neuroprotective in several brain disorders. Further they attenuate the amyloid plaques and protein aggregation which are the triggering factors in the Alzheimer's and Parkinson's respectively. In case of Huntington disease and Multiple sclerosis they help in improving the psychomotor symptoms and stimulate remyelination thus acting as neuroprotective. This article reviews the potential of statins in treating neurodegenerative disorders along with a brief discussion on the safety concerns associated with use of statins and human clinical trial data linked with re-tasking statins for neurodegenerative disorders along with the regulatory perspectives involved with the drug repositioning.

摘要

影响大量人群的神经退行性疾病构成了巨大的临床挑战。这些疾病通过损害作为大脑基本单元细胞的神经元来影响个体的生活质量。由于现有的治疗选择无法满足临床需求,临床医生面临着抑制这些疾病进展的严峻挑战。因此,对症治疗这些疾病是无奈之举。研究人员的目标是在这一领域引入更新的疗法,而引入一种新分子需要漫长的研发时间。因此,与耗时且昂贵的药物发现和开发周期相比,药物重新利用/重新定位可能是更好的替代方法。目前,可以看到一种向药物重新利用转变的范式。先前已被批准作为抗高脂血症药物的他汀类药物正处于重新利用药物研究的前沿。由于其抗炎和抗氧化特性,他汀类药物在几种脑部疾病中具有神经保护作用。此外,它们可减轻分别是阿尔茨海默病和帕金森病触发因素的淀粉样斑块和蛋白质聚集。在亨廷顿病和多发性硬化症的情况下,它们有助于改善精神运动症状并刺激髓鞘再生,从而起到神经保护作用。本文综述了他汀类药物在治疗神经退行性疾病方面的潜力,同时简要讨论了与使用他汀类药物相关的安全问题以及与将他汀类药物重新用于神经退行性疾病相关的人体临床试验数据,以及药物重新定位所涉及的监管观点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/927f/8663947/3526f1007cb7/fx1.jpg

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