Menozzi Elisa, Schapira Anthony H V
Aligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, Maryland, USA.
Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, London, United Kingdom; email:
Annu Rev Pharmacol Toxicol. 2025 Jan;65(1):237-258. doi: 10.1146/annurev-pharmtox-022124-033653. Epub 2024 Dec 17.
The increasing prevalence of Parkinson disease (PD) highlights the need to develop interventions aimed at slowing or halting its progression. As a result of sophisticated disease modeling in preclinical studies, and refinement of specific clinical/genetic/pathological profiles, our understanding of PD pathogenesis has grown over the years, leading to the identification of several targets for disease modification. This has translated to the development of targeted therapies, many of which have entered clinical trials. Nonetheless, up until now, none of these treatments have satisfactorily shown disease-modifying effects in PD. In this review, we present the most up-to-date disease-modifying pharmacological interventions in the clinical trial pipeline for PD. We focus on agents that have reached more advanced stages of clinical trials testing, highlighting both positive and negative results, and critically reflect on strengths, weaknesses, and challenges of current disease-modifying therapeutic avenues in PD.
帕金森病(PD)患病率的不断上升凸显了开发旨在减缓或阻止其进展的干预措施的必要性。由于临床前研究中复杂的疾病建模以及特定临床/遗传/病理特征的细化,多年来我们对PD发病机制的理解不断深入,从而确定了几个疾病修饰靶点。这已转化为靶向治疗的开发,其中许多已进入临床试验。尽管如此,到目前为止,这些治疗方法在PD中均未令人满意地显示出疾病修饰作用。在本综述中,我们介绍了PD临床试验管道中最新的疾病修饰药理学干预措施。我们重点关注已进入临床试验测试更高级阶段的药物,突出阳性和阴性结果,并批判性地反思当前PD疾病修饰治疗途径的优势、劣势和挑战。