Synonyms: Nerve Growth Factor gene therapy
Therapy Type: Gene/Stem Cell
Target Type: Other (timeline)
Condition(s): Alzheimer's Disease
U.S. FDA Status: Alzheimer's Disease (Discontinued)
Company: Sangamo BioSciences, Inc.
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.
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.
- Special Delivery: NGF Trial Puts Growth Factor Where It’s Needed
- Madrid: Clinical Trials Update—Where Do Things Stand?
- Growth Factor Therapy: Safe in Phase 1, Awaiting Efficacy Data
- NGF, Galantamine Rescue Anti-NGF Model of Alzheimer's
- NGF Gene Therapy Trial Begins
- Rafii MS, Baumann TL, Bakay RA, Ostrove JM, Siffert J, Fleisher AS, Herzog CD, Barba D, Pay M, Salmon DP, Chu Y, Kordower JH, Bishop K, Keator D, Potkin S, Bartus RT. A phase1 study of stereotactic gene delivery of AAV2-NGF for Alzheimer's disease. Alzheimers Dement. 2014 Jan 7; PubMed.
- Smith DE, Roberts J, Gage FH, Tuszynski MH. Age-associated neuronal atrophy occurs in the primate brain and is reversible by growth factor gene therapy. Proc Natl Acad Sci U S A. 1999 Sep 14;96(19):10893-8. PubMed.
- Herzog CD, Bishop KM, Brown L, Wilson A, Kordower JH, Bartus RT. Gene transfer provides a practical means for safe, long-term, targeted delivery of biologically active neurotrophic factor proteins for neurodegenerative diseases. Drug Deliv Transl Res. 2011 Oct;1(5):361-82. PubMed.
- Mandel RJ. CERE-110, an adeno-associated virus-based gene delivery vector expressing human nerve growth factor for the treatment of Alzheimer's disease. Curr Opin Mol Ther. 2010 Apr;12(2):240-7. PubMed.
- Bartus RT, Baumann TL, Siffert J, Herzog CD, Alterman R, Boulis N, Turner DA, Stacy M, Lang AE, Lozano AM, Olanow CW. Safety/feasibility of targeting the substantia nigra with AAV2-neurturin in Parkinson patients. Neurology. 2013 Apr 30;80(18):1698-701. PubMed.
- Hickey P, Stacy M. AAV2-neurturin (CERE-120) for Parkinson's disease. Expert Opin Biol Ther. 2013 Jan;13(1):137-45. PubMed.