Gene Therapy for Alzheimer's Disease

$2,010,177P01FY2005AGNIH

Salk Institute For Biological Studies, La Jolla CA

Investigators

Linked publications & trials

Paper 29535375 Paper 29045838 Paper 28130011 Paper 28067668 Paper 27558862 Paper 27525439 Paper 27466341 Paper 27419933 Paper 26948893 Paper 26903653 Paper 26620558 Paper 26489892 Paper 26388203 Paper 26341908 Paper 26302439 Paper 26202279 Paper 25803611 Paper 25788688 Paper 25673831 Paper 25533483 Paper 25505106 Paper 25448159 Paper 25173807 Paper 25126588 Paper 25093680 Paper 25024337 Paper 25022790 Paper 24885390 Paper 24825898 Paper 24813892 Paper 24462903 Paper 24068826 Paper 23935974 Paper 23626796 Paper 23413261 Paper 23401561 Paper 23392688 Paper 23384597 Paper 23313024 Paper 23254192 Paper 23223568 Paper 23182244 Paper 23152192 Paper 22989354 Paper 22833673 Paper 22810100 Paper 22647715 Paper 22528101 Paper 22514658 Paper 22508489 Paper 22492998 Paper 22456708 Paper 22314685 Paper 22281106 Paper 22229116 Paper 22211740 Paper 22150925 Paper 22112803 Paper 22066148 Paper 22064070 Paper 21998872 Paper 21994367 Paper 21928509 Paper 21860085 Paper 21403389 Paper 21368891 Paper 21358740 Paper 21304989 Paper 21296890 Paper 21257908 Paper 21103359 Paper 21045796 Paper 20970422 Paper 20679195 Paper 20559548 Paper 20554871 Paper 20445049 Paper 20433905 Paper 20413653 Paper 20181623 Paper 20140000 Paper 20091183 Paper 19944097 Paper 19932737 Paper 19931251 Paper 19864570 Paper 19726646 Paper 19660551 Paper 19651612 Paper 19587288 Paper 19551456 Paper 19535597 Paper 19416837 Paper 19321231 Paper 19198615 Paper 19176820 Paper 19166511 Paper 19135265 Paper 19014502 Paper 19013154

Abstract

DESCRIPTION (provided by applicant): The aim of this Program Project is to develop reliable, safe, and rational gene transfer procedures to repair or replace neurotransmitter function in relevant animal models of Alzheimer's Disease (AD). Project 1 focuses on the uses of lentivirus to replace age related decline of the cholinergic system in aged rats by over expression of the CHAT gene regionally; protecting against age related cholinergic cell loss; and testing the therapeutic effects of these genes in the mouse by over expressing a human mutated form of APP. Project 4 will use lentivirus to over express Cre recombinase in transgenic mice with the LOX sites surrounding the CHAT, NGF and P75 genes respectively, and will cross mice with homologous knockout of p75 and NGF gene, with mice over expressing a human mutation of the APP gene, to directly determine the interaction between these related genes. Project 5 will test the hypothesis that development of Alzheimer's disease is due to multiple deficits or "stresses" which lead to pathology. Project 3 will optimize in vivo vectors for gene therapy in primates by comparing AAV and lentivirus for amount, duration and safety of gene expression. In Project 6 recombinant lentiviral vectors expressing mutant PS1 or APP in developing transgenic models of amyloid deposition in the brain, will examine the interactions of these genes in vivo. The Vector Core, will support high recombinant vectors to all projects. The Projects/Cores in this PPG have been chosen for their relevance in addressing these problems and securing a rational approach to gene therapy in AD. The interdependency of resources and skills between Projects/Cores, as well as our past success with this PPG, support the argument that the Program Project is the most efficient and cost-effective way to address these issues.

View original record on NIH RePORTER →