Nerve Growth Factor and Brain-Derived Neurotrophic Factor Gene Therapy for Alzheimer’s Disease
摘要
Neurotrophic factors are endogenous brain proteins that influence neuronal function and survival throughout life, from neural development through late aging. In animal models of Alzheimer’s disease (AD), the growth factors nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) prevent neuronal death and activate neuronal function. NGF targets cholinergic systems in the brain, while BDNF influences cortical neurons. BDNF in particular prevents the death of cortical neurons, activates the functional state of neurons, builds new synaptic proteins, and improves learning and memory. In a previous clinical trial of nerve growth factor (NGF) gene therapy in Alzheimer’s patients (NCT00017940, June 2001), we learned that growth factors unequivocally elicit classic “trophic responses” from degenerating neurons in AD. In an ongoing clinical trial (NCT05040217, June 2021), we are determining whether gene delivery of BDNF in patients with AD and Mild Cognitive Impairment (MCI) will prevent or slow memory loss or actually improve memory.