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.
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