Prodromal Parkinson’s disease: hype or hope for disease-modification trials?  

作　　者：Philipp Mahlknecht Kathrin Marini Mario Werkmann Werner Poewe Klaus Seppi 

机构地区：[1]Department of Neurology,Innsbruck Medical University,6020 Innsbruck,Austria

出　　处：《Translational Neurodegeneration》2022年第1期777-789,共13页转化神经变性病（英文）

基　　金：There was no specific funding for this article.P.M.:reports lecture fees from Boston Scientific outside the submitted work and a grant from the Tiroler Wissenschaftsförderung(Grant UNI-0404/2245);K.M.:has been supported by a grant from the Tiroler Wissenschaftsförderung(Grant UNI-0404/2245);M.W.:Nothing to report.W.P.:reports personal fees from Alterity,AbbVie,Affiris,AstraZeneca,BIAL,Biogen,Britannia,Lilly,Lundbeck,Neuroderm,Neurocrine,Denali Pharmaceuticals,Novartis,Orion Pharma,Roche,Takeda,Teva,UCB,and Zambon(consultancy and lecture fees in relation to clinical drug development programs for PD);royalties from Thieme,Wiley Blackwell,Oxford University Press,and Cambridge University Press;and grant support from MJFF;EU FP7,and Horizon 2020 outside the submitted work.K.S.:reports personal fees from Teva,UCB,Lundbeck,AOP Orphan Pharmaceuticals AG,Roche,Grünenthal,Stada,Licher Pharma,Biogen,and Abbvie;honoraria from the International Parkinson and Movement Disorders Society;and research grants from FWF Austrian Science Fund,Michael J.Fox Foundation,and AOP Orphan Pharmaceuticals AG,outside the submitted work.

摘　　要：The ultimate goal in Parkinson’s disease (PD) research remains the identification of treatments that are capable of slowing or even halting the progression of the disease. The failure of numerous past disease-modification trials in PD has been attributed to a variety of factors related not only to choosing wrong interventions, but also to using inadequate trial designs and target populations. In patients with clinically established PD, neuronal pathology may already have advanced too far to be modified by any intervention. Based on such reasoning, individuals in yet prediagnostic or prodromal disease stages, may provide a window of opportunity to test disease-modifying strategies. There is now sufficient evidence from prospective studies to define diagnostic criteria for prodromal PD and several approaches have been studied in observational cohorts. These include the use of PD-risk algorithms derived from multiple established risk factors for disease as well as follow-up of cohorts with single defined prodromal markers like hyposmia, rapid eye movement sleep behavior disorders, or PD gene carriers. In this review, we discuss recruitment strategies for disease-modification trials in various prodromal PD cohorts, as well as potential trial designs, required trial durations, and estimated sample sizes. We offer a concluding outlook on how the goal of implementing disease-modification trials in prodromal cohorts might be achieved in the future.

关 键 词：NEUROPROTECTION PRECLINICAL Prevention Epidemiology Probability Randomized controlled trial PREVENTIVE NEUROPROTECTIVE 

分 类 号：R742.5[医药卫生—神经病学与精神病学]