Background

CERE-110 was a gene-therapy approach for neuroprotective treatment of Alzheimer's disease. It employed injection of an AAV2-based vector for expression of the gene encoding the trophic protein nerve growth factor (NGF) into the nucleus basalis of Meynert, a cholinergic brain area that degenerates in the disease. The approach grew out of research showing that local NGF delivery was able to slow age-related neurodegeneration in mouse models and rhesus monkeys, and it has been in small clinical trials since 2000 (Sep 2002 news; Smith et al., 1999; Dec 1999 news). CERE-110 was initially developed by by Ceregene, which was bought by Sangamo BioSciences in 2013. 

Findings

A pilot study of a previous form of NGF gene therapy—delivered via genetically engineered autologous fibroblasts—reported safety and hints for a potential long-term benefit for locally produced NGF (Apr 2005 news; Sep 2006 conference news).

Between 2004 and 2010, a two-year, open-label Phase 1 trial conducted in San Diego and Chicago investigated the safety, tolerability, and biological activity of increasing doses of CERE-110 delivered directly by bilateral stereotactic surgery into 10 patients with mild to moderate Alzheimer's disease. In this trial, CERE-110 was reported to have been safe and well-tolerated for up to two years of observation. Stable expression and biological activity were reported based on postmortem pathology (Nov 2013 conference news; Rafii et al., 2014).

From 2009 to 2015, a multicenter, sham-surgery controlled Phase 2 trial run by the ADCS evaluated CERE-110 in 49 people with mild to moderate AD for its ability to slow decline on the ADAS-cog, NPI, and ADCS-ADL batteries and to measure efficacy on cognition, neuropsychiatric well-being, and activities of daily living. In this study, CERE-110 was again safe and well-tolerated, but ineffective. In April 2015, Sangamo announced it was terminating the program (see company press release).

For all trials of CERE-110, see clinicaltrials.gov.