23-07-08(11:34:12)
Authors:
1Armin Blesch, Ph.D., 1Leon Thal, M.D., 1Mary Pay, R.N., 1David Salmon, Ph.D., 1Adam Fleischer, M.D., 1David Barba, M.D., 2Zoe Arvanitakis, M.D., 2David Bennett, M.D., 3Roy Bakay, M.D., 4Steve Potkin, M.D., 5Kathie Bishop, Ph.D., 5Mehdi Gasmi, Ph.D., 1James Conner, Ph.D., 5Raymond Bartus, Ph.D., 1Mark H. Tuszynski, M.D., Ph.D.
Institutions:
Departments of 1Neurosciences, University of California-San Diego, 2Neurology and 3Neurosurgery, Rush University Medical Center, 4Neurology, University of California-Irvine, and 5Ceregene, Inc., San Diego
Title of abstract : NERVE GROWTH FACTOR (NGF) GENE THERAPY FOR ALZHEIMER’S DISEASE-AN UPDATE
Abstract text:
Neurotrophic factors potently stimulate cell function, prevent neuronal death and offer the potential to treat neurodegenerative disorders by preventing neuronal degeneration rather than compensating for cell loss after it has occurred. The implementation of clinical testing of growth factor therapy for neurological disease has been constrained by the dual need to achieve adequate concentrations of these proteins in specific brain regions containing degenerating neurons, and preventing growth factor spread to non-targeted regions to avoid adverse effects. Gene therapy is one of a limited number of potential methods for achieving these requirements. Numerous rodent and primate studies have shown that NGF stimulates the survival and function of basal forebrain cholinergic neurons, which undergo severe degeneration in Alzheimer’s disease (AD). Thus, NGF delivery may be a means for reducing the cholinergic component of cell degeneration in AD. Two phase 1 clinical trials of NGF gene transfer in Alzheimer’s disease have been conducted to date: an “ex vivo” and an “in vivo” gene therapy trial. Both of these trials supported the safety of NGF gene transfer to the human Alzheimer’s disease brain and provide the rationale for further clinical testing of NGF in a multi-center, sham surgery-controlled trial of Alzheimer’s disease scheduled to begin in the near future.
