Francesco Panza1, Giancarlo Logroscino, Bruno P Imbimbo, Vincenzo Solfrizzi. 1. aNeurodegenerative Disease Unit, Department of Basic Medicine, Neuroscience, and Sense Organs, University of Bari Aldo Moro, Bari bDepartment of Clinical Research in Neurology, University of Bari Aldo Moro, 'Pia Fondazione Cardinale G. Panico', Tricase, Lecce cResearch and Development Department, Chiesi Farmaceutici, Parma dGeriatric Medicine-Memory Unit and Rare Disease Centre, University of Bari Aldo Moro, Bari, Italy.
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.
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 diseasepatients treated. Among passive immunotherapeutics, two Phase III clinical trials in mild-to-moderate Alzheimer's diseasepatients 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 diseasepatients. A third Phase III study with solanezumab is ongoing in mildly affected Alzheimer's diseasepatients 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 diseasepatients, 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.