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帕金森病的基因靶向临床试验:从肿瘤学的成功中吸取经验。

Genetically Targeted Clinical Trials in Parkinson's Disease: Learning from the Successes Made in Oncology.

机构信息

Herantis Pharma Plc, Bertel Jungin Aukio 1, 02600 Espoo, Finland.

Department Health Sciences, Umeå University, 907 36 Umeå, Sweden.

出版信息

Genes (Basel). 2021 Sep 28;12(10):1529. doi: 10.3390/genes12101529.

Abstract

Clinical trials in neurodegenerative disorders have been associated with high rate of failures, while in oncology, the implementation of precision medicine and focus on genetically defined subtypes of disease and targets for drug development have seen an unprecedented success. With more than 20 genes associated with Parkinson's disease (PD), most of which are highly penetrant and often cause early onset or atypical signs and symptoms, and an increasing understanding of the associated pathophysiology culminating in dopaminergic neurodegeneration, applying the technologies and designs into the field of neurodegeneration seems a logical step. This review describes some of the methods used in oncology clinical trials and some attempts in Parkinson's disease and the potential of further implementing genetics, biomarkers and smart clinical trial designs in this disease area.

摘要

神经退行性疾病的临床试验一直与高失败率相关,而在肿瘤学领域,精准医学的实施以及对遗传定义的疾病亚型和药物开发靶点的关注,带来了前所未有的成功。帕金森病(PD)相关的基因超过 20 个,其中大多数具有高度外显性,且常导致疾病的早发或非典型体征和症状,并且对相关病理生理学的认识不断深入,最终导致多巴胺能神经退行性变。因此,将这些技术和设计应用于神经退行性疾病领域似乎是合乎逻辑的一步。本综述描述了肿瘤学临床试验中使用的一些方法,以及在帕金森病中进行的一些尝试,以及在该疾病领域进一步实施遗传学、生物标志物和智能临床试验设计的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3372/8535305/755707a8b672/genes-12-01529-g001.jpg

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