LeWitt P A
Department of Neurology, Psychiatry and Behavioral Neuroscience, Wayne State University School of Medicine, The William Beaumont Hospital Research Institute, Royal Oak, Michigan, USA.
J Neural Transm Suppl. 2006(71):113-22.
Although still a disorder of unknown etiology, Parkinson's disease (PD) has provided a number of clues that have led to clinical trials of neuroprotection. For example, defects in mitochondrial metabolism and evidence for oxidative stress in PD have fostered therapeutic interventions aimed at slowing disease progression. More than a dozen compounds already have been tested in PD for disease modification, and others are in planning stages for clinical trials. The challenge is to find a highly effective therapy halting disease progression (beyond the relatively modest clinical effect exemplified by recent findings with coenzyme Q-10 treatment administered at 1200mg/day). Clinical exam-based ratings and disability assessments still serve at providing the primary evidence of efficacy. However, with surrogate biomarkers such as radiotracer neuroimaging of the dopaminergic system, the pace of clinical investigation can be increased. Recent years have seen the utilization of more sensitive study methods in PD neuroprotection research, such as staggered wash-in, 2 x 2 factorial, and "futility" trial designs. The results of several ongoing PD neuroprotection trials are planned for release in the near future.
尽管帕金森病（PD）仍然是一种病因不明的疾病，但它已经提供了一些线索，这些线索促成了神经保护的临床试验。例如，PD中线粒体代谢缺陷和氧化应激证据促使了旨在减缓疾病进展的治疗干预措施。已经有十几种化合物在PD中进行了疾病修饰测试，其他化合物正处于临床试验的规划阶段。挑战在于找到一种能有效阻止疾病进展的疗法（超越每天服用1200毫克辅酶Q-10治疗所体现的相对适度的临床效果）。基于临床检查的评分和残疾评估仍然是提供疗效主要证据的方式。然而，通过诸如多巴胺能系统放射性示踪神经成像等替代生物标志物，可以加快临床研究的速度。近年来，在PD神经保护研究中采用了更敏感的研究方法，如交错导入、2×2析因和“无效性”试验设计。几项正在进行的PD神经保护试验的结果计划在不久的将来公布。
