Advances in progressive supranuclear palsy: new diagnostic criteria, biomarkers, and therapeutic approaches.
Advances in progressive supranuclear palsy: new diagnostic criteria, biomarkers, and therapeutic approaches.
复制标题
DOI：
10.1016/s1474-4422(17)30157-6
复制
发表时间：
2017-07
期刊：
影响因子：
--
通讯作者：
Höglinger GU
中科院分区：
文献类型：
--
作者：
Boxer AL;Yu JT;Golbe LI;Litvan I;Lang AE;Höglinger GU
进行性核上性麻痹（PSP），曾经被简单地认为是非典型帕金森综合征的常见原因，现在被认为是一系列与尸检中特定的四重复（4R）tau神经病理学相关的运动和行为综合征。目前还没有有效的治疗PSP的方法，但由于PSP在生物化学和遗传上与tau蛋白异常密切相关，因此对这种疾病进行新的tau导向疗法的临床试验的兴趣越来越大。这些新的tau疗法被设想通过降低tau毒性形式的脑水平或补偿tau功能的丧失而具有疾病修饰作用。为了最有效，这些治疗需要在疾病的早期阶段开始。最近发表了新的研究标准，可以识别PSP的早期形式并对全谱临床表型进行操作性诊断。这些标准和新的临床试验设计受益于PSP的MRI、生理和液体生物标志物开发的快速进展。由于tau病理学也是阿尔茨海默病和慢性创伤性脑病的核心，因此认为PSP的成功tau治疗将为其他神经退行性疾病的治疗提供信息。
Progressive supranuclear palsy (PSP), once simply considered a common cause of atypical parkinsonism is now recognized as a spectrum of motor and behavioral syndromes associated with a specific four repeat (4R) tau neuropathology at autopsy. There are currently no effective treatments for PSP, but because PSP is strongly linked biochemically and genetically to tau protein abnormalities, there is a growing interest in pursuing clinical trials of new tau-directed therapies for this disorder. Such new tau therapies are envisioned to have disease-modifying effects by reducing brain levels of toxic forms of tau or compensating for loss of tau function. To be most effective, these treatments will need to be initiated at early stages of disease. New research criteria that recognize early forms of PSP and operationalize diagnosis of the full spectrum of clinical phenotypes have recently been published. These criteria and new clinical trial designs have benefited from rapid advances in MRI, physiological and fluid biomarker development for PSP. As tau pathology is also central to Alzheimer’s disease and chronic traumatic encephalopathy, it is believed that a successful tau therapeutic for PSP would inform the treatment of other neurodegenerative diseases.