Neurotrophin gene therapy for Alzheimer’s disease

Abstract

In vitro and in vivo studies conducted over the last 20 years have shown that neurotrophic factors can prevent neuronal cell death and augment neuronal function in rodent and nonhuman primate models of neurodegenerative diseases. The translation of these studies into clinical trials has, initially, been slowed by the inability to deliver growth factors in a localized manner at sufficiently high doses to obtain therapeutic effects in the adult brain, without significant adverse effects. Recent progress in the targeted delivery of neurotrophic factors by gene therapy allows investigators to determine for the first time, in clinical trials, whether growth factors can influence neuronal function in the diseased human nervous system. A Phase I study of cellular nerve growth factor delivery in subjects with Alzheimer’s disease has provided promising results. Additional studies examining the neuroprotective effects of glial cell-derived neurotrophic factor family ligands in Parkinson’s disease have been conducted, or are planned for the near future. Taken together, these studies might be able to determine whether therapeutic effects observed in animal models of neuronal degeneration can be translated into novel, neuroprotective treatments for neurological disease.