Stoker Thomas B, Barker Roger A
John van Geest Centre for Brain Repair, Department of Clinical Neurosciences, University of Cambridge, Forvie Site, Robinson Way, Cambridge, CB2 0PY, UK.
Department of Neurology, Norfolk and Norwich University Hospital, Norwich, UK.
F1000Res. 2020 Jul 31;9. doi: 10.12688/f1000research.25634.1. eCollection 2020.
Parkinson's disease (PD) is a common neurodegenerative disease typified by a movement disorder consisting of bradykinesia, rest tremor, rigidity, and postural instability. Treatment options for PD are limited, with most of the current approaches based on restoration of dopaminergic tone in the striatum. However, these do not alter disease course and do not treat the non-dopamine-dependent features of PD such as freezing of gait, cognitive impairment, and other non-motor features of the disorder, which often have the greatest impact on quality of life. As understanding of PD pathogenesis grows, novel therapeutic avenues are emerging. These include treatments that aim to control the symptoms of PD without the problematic side effects seen with currently available treatments and those that are aimed towards slowing pathology, reducing neuronal loss, and attenuating disease course. In this latter regard, there has been much interest in drug repurposing (the use of established drugs for a new indication), with many drugs being reported to affect PD-relevant intracellular processes. This approach offers an expedited route to the clinic, given that pharmacokinetic and safety data are potentially already available. In terms of better symptomatic therapies that are also regenerative, gene therapies and cell-based treatments are beginning to enter clinical trials, and developments in other neurosurgical strategies such as more nuanced deep brain stimulation approaches mean that the landscape of PD treatment is likely to evolve considerably over the coming years. In this review, we provide an overview of the novel therapeutic approaches that are close to, or are already in, clinical trials.
帕金森病（PD）是一种常见的神经退行性疾病，其典型特征为运动障碍，包括运动迟缓、静止性震颤、肌强直和姿势不稳。PD的治疗选择有限，目前大多数方法基于恢复纹状体中的多巴胺能张力。然而，这些方法并不能改变疾病进程，也无法治疗PD的非多巴胺依赖特征，如步态冻结、认知障碍以及该疾病的其他非运动特征，而这些特征往往对生活质量影响最大。随着对PD发病机制的认识不断深入，新的治疗途径正在涌现。这些途径包括旨在控制PD症状且无现有治疗方法所出现的问题副作用的治疗，以及旨在减缓病理进程、减少神经元损失和减轻疾病进程的治疗。在后一方面，药物重新利用（将已上市药物用于新适应症）备受关注，许多药物据报道会影响与PD相关的细胞内过程。鉴于药代动力学和安全性数据可能已经存在，这种方法为进入临床提供了一条捷径。就更好的具有再生作用的对症治疗而言，基因治疗和基于细胞的治疗已开始进入临床试验，其他神经外科策略的发展，如更精细的深部脑刺激方法，意味着PD治疗格局在未来几年可能会有很大变化。在这篇综述中，我们概述了接近或已进入临床试验的新型治疗方法。
