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帕金森病的疾病修饰治疗:多发性硬化的启示。

Disease-modifying therapies for Parkinson disease: lessons from multiple sclerosis.

机构信息

Edmond J Safra Program in Parkinson's Disease, Krembil Research Institute, Toronto Western Hospital, University Health Network, Toronto, Ontario, Canada.

Division of Neurology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada.

出版信息

Nat Rev Neurol. 2024 Dec;20(12):724-737. doi: 10.1038/s41582-024-01023-0. Epub 2024 Oct 7.

Abstract

The development of disease-modifying therapies (DMTs) for neurological disorders is an important goal in modern neurology, and the associated challenges are similar in many chronic neurological conditions. Major advances have been made in the multiple sclerosis (MS) field, with a range of DMTs being approved for relapsing MS and the introduction of the first DMTs for progressive MS. By contrast, people with Parkinson disease (PD) still lack such treatment options, relying instead on decades-old therapeutic approaches that provide only symptomatic relief. To address this unmet need, an in-person symposium was held in Toronto, Canada, in November 2022 for international researchers and experts in MS and PD to discuss strategies for advancing DMT development. In this Roadmap article, we highlight discussions from the symposium, which focused on therapeutic targets and preclinical models, disease spectra and subclassifications, and clinical trial design and outcome measures. From these discussions, we propose areas for novel or deeper exploration in PD using lessons learned from therapeutic development in MS. In addition, we identify challenges common to the PD and MS fields that need to be addressed to further advance the discovery and development of effective DMTs.

摘要

神经疾病的疾病修饰疗法(DMT)的发展是现代神经病学的一个重要目标,许多慢性神经疾病的相关挑战也类似。在多发性硬化症(MS)领域已经取得了重大进展,一系列 DMT 已被批准用于缓解复发型 MS,并且首次引入了用于进展型 MS 的 DMT。相比之下,帕金森病(PD)患者仍然缺乏这种治疗选择,只能依赖于数十年前的治疗方法,这些方法只能提供症状缓解。为了解决这一未满足的需求,2022 年 11 月在加拿大多伦多举行了一次现场研讨会,来自 MS 和 PD 的国际研究人员和专家讨论了推进 DMT 开发的策略。在这篇路线图文章中,我们强调了研讨会的讨论内容,重点讨论了治疗靶点和临床前模型、疾病谱和亚分类,以及临床试验设计和结果衡量标准。从这些讨论中,我们提出了使用从 MS 治疗开发中吸取的经验教训,在 PD 中进行新的或更深入探索的领域。此外,我们还确定了 PD 和 MS 领域共同面临的需要解决的挑战,以进一步推进有效 DMT 的发现和开发。

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