CERE-110, an adeno-associated virus-based gene delivery vector expressing human nerve growth factor for the treatment of Alzheimer's disease.

To date, only five drugs have been approved for the treatment of Alzheimer's disease (AD); however, these agents impact the symptoms rather than the progression of the disease. It is well established that nerve growth factor (NGF) enhances the function and survival of basal forebrain cholinergic neurons that are vulnerable in AD. However, NGF does not cross the blood-brain barrier, and intraventricular NGF injections in animals and humans were associated with significant side effects. Adeno-associated virus (AAV)-based gene delivery is a novel technology being developed for administration of NGF to the brain to treat AD symptoms and progression. Indeed, the efficacy of ex vivo gene delivery was demonstrated in patients with AD who experienced improvements in cerebral metabolism and cognition compared with pre-operative function without adverse events. CERE-110 (AAV2-NGF), under development by Ceregene Inc, is an AAV serotype 2-based vector expressing human NGF delivered to the nucleus basalis of Meynert by stereotactic injection for the treatment of AD. Animal studies have established the preclinical efficacy of CERE-110, revealing an excellent safety profile. CERE-110 has passed phase I clinical testing and a multicenter phase II clinical trial has commenced. CERE-110 is a promising candidate for the treatment of AD.