From the Department of Neurology, McGill University, Montreal, Quebec, Canada.
Neurology. 2022 Aug 16;99(7 Suppl 1):19-25. doi: 10.1212/WNL.0000000000200235.
As neuroprotective therapies continue to be advanced against neurodegenerative synucleinopathies, such as Parkinson disease (PD), dementia with Lewy bodies (DLBs), and multiple system atrophy, increasing attention is turning to the prodromal stages of disease. Treatments at the prodromal stage have the compelling advantages of being applied early enough to make a meaningful difference and can be tested without confounding by symptomatic therapies used for clinical PD/DLB. As it currently stands, patients with idiopathic/isolated REM sleep behavior disorder (iRBD) represent the only large existing cohort of untreated prodromal PD/DLB that would be ready to start a clinical trial now. Several thousand patients with RBD are currently being followed in research-based clinics, and more than 80% of them will develop a full neurodegenerative synucleinopathy. Research into RBD phenoconversion rates and predictors has advanced considerably, and we are now able to generate increasingly precise estimates of progression rates, can select stratification markers to enrich trials, and are able to understand the progression and sample size implications of different primary outcome measures. This review will outline the potential for neuroprotective trials in iRBD, including the pathophysiologic mechanisms with the most promise to target in iRBD, selection criteria for inclusion, and the optimal primary trial outcome measures to choose.
随着神经保护性疗法在神经退行性突触核蛋白病（如帕金森病[PD]、路易体痴呆[DLB]和多系统萎缩）方面不断得到推进，人们越来越关注疾病的前驱阶段。在疾病前驱阶段进行治疗具有明显的优势，即可以尽早应用，从而产生有意义的影响，并且可以在不与用于临床 PD/DLB 的症状性治疗相混淆的情况下进行测试。目前，特发性/孤立性 REM 睡眠行为障碍（iRBD）患者是唯一大量存在的未经治疗的前驱 PD/DLB 患者群体，他们现在已经准备好开始临床试验。目前，有数千名 RBD 患者正在研究型诊所接受随访，其中超过 80%的患者将发展为完全的神经退行性突触核蛋白病。关于 RBD 表型转化率和预测因素的研究已经取得了相当大的进展，我们现在能够更精确地估计进展率，可以选择分层标志物来丰富试验，并能够了解不同主要结局指标的进展和样本量影响。这篇综述将概述 iRBD 中神经保护性试验的潜力，包括最有希望针对 iRBD 的病理生理机制、纳入标准以及最佳的主要试验结局指标选择。
