Is there still any hope for amyloid-based immunotherapy for Alzheimer's disease?

Abstract

PURPOSE OF REVIEW:

We reviewed clinical trials on active and passive anti-β-amyloid (Aβ) immunotherapy for the treatment of Alzheimer's disease with a particular focus on monoclonal antibodies against Aβ.

RECENT FINDINGS:

Studies on anti-Alzheimer's disease immunotherapy published in the period from January 2012 to October 2013 were reviewed.

SUMMARY:

Both active and passive anti-Aβ immunotherapies were shown to clear brain Aβ deposits. However, an active anti-Aβ vaccine (AN1792) has been discontinued because it caused meningoencephalitis in 6% of Alzheimer's disease patients treated. Among passive immunotherapeutics, two Phase III clinical trials in mild-to-moderate Alzheimer's disease patients with bapineuzumab, a humanized monoclonal antibody directed at the N-terminal sequence of Aβ, were disappointing. Another antibody, solanezumab, directed at the mid-region of Aβ, failed in two Phase III clinical trials in mild-to-moderate Alzheimer's disease patients. A third Phase III study with solanezumab is ongoing in mildly affected Alzheimer's disease patients based on encouraging results in this subgroup of patients. Second-generation active Aβ vaccines (ACC-001, CAD106, and Affitope AD02) and new passive anti-Aβ immunotherapies (gantenerumab and crenezumab) are being tested in prodromal Alzheimer's disease patients, in presymptomatic individuals with Alzheimer's disease-related mutations, or in asymptomatic individuals at risk of developing Alzheimer's disease to definitely test the Aβ cascade hypothesis of Alzheimer's disease.

• Authors: Francesco Panza, Giancarlo Logroscino, Bruno P Imbimbo, Vincenzo Solfrizzi
• Journal: Current opinion in psychiatry (Curr Opin Psychiatry) Vol. 27 Issue 2 Pg. 128-37 (Mar 2014) ISSN: 1473-6578 [Electronic] United States
• PMID: 24445401 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Amyloid beta-Peptides
• Antibodies, Monoclonal

Topics

• Alzheimer Disease (immunology, therapy)
• Amyloid beta-Peptides (immunology, therapeutic use)
• Animals
• Antibodies, Monoclonal (therapeutic use)
• Clinical Trials as Topic
• Disease Models, Animal
• Humans
• Immunotherapy (methods)