A new tool in the battle against Alzheimer's disease and aging: ex vivo gene therapy.

Alzheimer's disease (AD) is the most common cause of severe dementia in the aging population and is caused by a loss of many different neural systems throughout the brain associated with memory. Amongst the many neural systems affected, large cholinergic projection neurons that innervate large regions of cortex are particularly vulnerable. Thus, boosting cholinergic neuronal function and survival has been a focus of the few drugs currently available for this disorder. Nerve growth factor (NGF) is the archetypical protein discovered in the 1960s that is able to both increase survival and functioning of cholinergic neurons. However, the blood-brain barrier does not allow penetration of this protein into the brain. A phase 1 clinical trial recently published in the journal Nature Medicine utilized a unique ex vivo gene therapy approach to deliver NGF directly to the basal forebrain of AD patients. Despite the need for further testing, their report illustrated a mild but significant therapeutic benefit of NGF for the treatment of AD and provided important data concerning the safety and efficacy of ex vivo gene therapy in humans.