Studies in Dementia and Neurodegenerative Diseases

痴呆症和神经退行性疾病研究

• 批准号: 8148373
• 负责人: Dimitrios Kapogiannis
• 金额: $ 45万
• 依托单位: NATIONAL INSTITUTE ON AGING
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8148373
• 关键词: Dementia; Neurodegenerative Disorders

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.

Exendin-4治疗阿尔茨海默氏病的临床试验。 NIA与神经科学实验室的研究人员合作，我们制作并发表了其他临床前证据，证明了Exendin-4在阿尔茨海默氏病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发现，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治疗的安全性和功效（II/III期）对早期的阿尔茨海默氏病参与者的治疗。这项研究于2010年1月获得了机构审查委员会的批准。数据安全监控委员会于2010年6月召集，并批准了该试验的核心。 2010年7月，宾夕法尼亚大学的莱斯利·肖（Leslie Shaw）博士结束了合同，为这项研究提供了实验室支持。目前正在进行参与者的入学率。 150名参与者将根据早期AD的症状和体征，认知性能和低脑脊液淀粉样蛋白β的特征，参加治疗，其中230名潜在的参与者将接受筛查。筛查过程预计将持续两年，预计将产生有关认知和行为性能，血浆和脑脊液生物标志物水平以及结构和功能性MRI和MRS的丰富横截面数据，这些数据将用于测试有关AD病原体的假设。招收的参与者被随机分为两组之一（Exendin-4与安慰剂），并将定期遵循三年的时间。 Exendin-4的疗效将主要根据总体认知性能（ADAS-COG）和功能（盒子的CDR-SUM）测量进行评估，其次是其他行为和认知绩效指标，结构和功能性MRI的变化以及大脑流体和血浆生物标志物的变化。所有患者均纳入临床研究部门。 MRI和MRS研究是在NIA 3T MRI设施进行的。生物流体样本被发送到NIA神经科学，神经源性和临床研究的NIA实验室，以及宾夕法尼亚大学莱斯利·肖博士的实验室。 额颞叶变性的遗传和表型表征研究。与国家神经系统疾病和中风研究所认知神经科学部门的研究人员合作，我们对额颞痴呆，皮质性癌综合征和相关疾病的个体进行自然史研究。作为这些研究的一部分，我们发表了在额颞痴呆患者中引用的多囊体蛋白2b中新型错义突变的发现。我们还发表了意识运动的关联与皮质综合征的额叶灰质体积损失。