Studies in Dementia and Neurodegenerative Diseases

Exendin-4治疗阿尔茨海默病的临床试验。与NIA神经科学实验室的研究人员合作，我们制作并发表了额外的临床前证据，证明Exendin-4在阿尔茨海默病的细胞和动物模型中的有益作用。基于这些和类似的先前发表的研究结果，我们设计了一项双盲随机安慰剂对照临床试验，以评估Exendin-4治疗早期阿尔茨海默病的安全性和有效性（II/III期）。该研究于2010年1月获得了机构审查委员会的批准。数据安全监测委员会于2010年6月召开会议，批准启动试验。2010年7月，我们与宾夕法尼亚大学的Leslie Shaw博士签订了一份合同，为这项研究提供实验室支持。目前正在进行参加者的登记工作。150名参与者将根据早期阿尔茨海默病的症状和体征、认知能力和低脑脊液淀粉样蛋白的特征，从230名潜在参与者中筛选出来。该筛选过程预计将持续两年，预计将产生丰富的认知和行为表现、血浆和脑脊液生物标志物水平以及结构和功能MRI和MRS的横断面数据，这些数据将用于测试关于AD发病机制的假设。入选的参与者被随机分配到两组（Exendin-4 vs.安慰剂）中的一组，并将定期随访三年。Exendin-4的疗效将主要根据总体认知表现（ADAS-cog）和功能（CDR-sum of boxes）测量进行评估，其次根据其他行为和认知表现测量、结构和功能MRI和MRS的变化以及脑脊液和血浆生物标志物的变化进行评估。所有患者均在临床研究科登记。MRI和MRS研究在NIA 3T MRI设施进行。生物流体样本被送到NIA的神经科学、神经遗传学和临床研究实验室，以及宾夕法尼亚大学莱斯利·肖博士的实验室。

A clinical Trial of Exendin-4 for the treatment of Alzheimer's Disease. In collaboration with researchers in the Laboratory of Neurosciences, NIA, we produced and published additional preclinical evidence for beneficial effects of Exendin-4 in cellular and animal models of Alzheimers disease. Based on these and similar previously published findings, we designed a double blind randomized placebo-controlled clinical trial to assess the safety and efficacy (phase II/III) of Exendin-4 treatment in participants with early Alzheimers disease. This study acquired Institutional Review Board approval in January 2010. The Data Safety Monitoring Board convened in June 2010 and approved the intiation of the trial. A contract was concluded with Dr. Leslie Shaw from the University of Pennsylvania in July 2010 to provide laboratory support for the study. Enrolment of participants is currently under way. 150 participants will be enrolled into treatment on the basis of symptoms and signs characteristic of early AD, cognitive performance and low cerebrospinal fluid amyloid-beta, out of 230 potential participants who will undergo screening. The screening process is expected to last two years and is expected to generate rich cross-sectional data on cognitive and behavioral performance, plasma and cerebrospinal fluid biomarker levels and structural and functional MRI and MRS, which will be used to test hypotheses on AD pathogenesis. Enrolled participants are randomly being assigned into one of two groups (Exendin-4 vs. Placebo) and will be followed at regular intervals for three years. The efficacy of Exendin-4 will be primarily assessed in terms of overall cognitive performance (ADAS-cog) and function (CDR-sum of boxes) measures and secondarily in terms of other behavioral and cognitive performance measures, changes on structural and functional MRI and MRS and changes in cerebrospinal fluid and plasma biomarkers. All patients are enrolled at the Clinical Research Branch. MRI and MRS studies are performed at the NIA 3T MRI facility. Biofluid samples are being sent to the NIA labs of Neurosciences, Neurogenetics and Clinical Investigations and to the Laboratory of Dr. Leslie Shaw at the University of Pennsylvania. Genetic and phenotypic characterization studies in Frontotemporal Lobar Degeneration. In collaboration with researchers at the Cognitive Neuroscience Section of the National Institute of Neurological Disorders and Stroke, we perform natural history studies in individuals with Frontotemporal Dementia, Corticobasal syndrome and related disorders. As part of these studies, we published the finding of a novel missense mutation in charged multivesicular body protein 2B in a patient with Frontotemporal Dementia. We also published the association of ideomotor apraxia with frontal gray matter volume loss in corticobasal syndrome.