Name:	MABT5102A
Therapeutic Applications:	Mild to moderate Alzheimer disease
Therapy Types:	humanized monoclonal antibody against Aβ
Mechanisms:	Designed to bind and remove the Aβ peptide that accumulates in the brain.
Development Status:	investigational in U.S.
FDA Phase:	Phase II/IIa/IIb
Primary Medical Role:	Immunotherapy approaches to the treatment of Alzheimer's disease are based on the ability of antibodies raised against Aβ peptides to bind to and clear Aβ from the brain, thus removing the peptide and inhibiting the damage to neurons that Aβ inflicts. Active immunotherapy involves inoculating patients with peptides and inducing an immune response to Aβ within the patient. The failed clinical trial of AN1792 was an example of this approach. This trial was suspended due to serious adverse effects in which a subset of patients developed encephalitis, or brain inflammation, an autoimmune disease effect of the inoculation. MABT5102A, in contrast, is a passive immunotherapy approach, in which patients are treated with humanized monoclonal antibodies with specificity to Aβ peptides. MABT5102A (crenezumab) has been shown to bind to oligomeric and fibrillar forms of Aβ with high affinity and to monomeric Aβ to a lesser degree (Adolfsson et al., 2012). In contrast to other passive immunization antibodies, such as Bapineuzumab and Solanezumab, which have an IgG1 backbone, MABT5102A has an IgG4 backbone which is thought to stimulate a milder microglial response and thus limit proinflammatory effects.
Role in Alzheimer's Disease:	MABT5102A (crenezumab)is a humanized monoclonal antibody, which binds to Aβ. Aβ is the main constituent of amyloid plaque in the brains of patients with Alzheimer's disease and is proposed to be causative in the development of the disease.
Pharmacological Role:	Anti-Aβ antibodies have been shown to prevent the accumulation of Aβ peptides in the brains of transgenic mouse models of AD (Schenk et al., 1999; Bard et al., 2000; DeMattos et al., 2001). Anti-Aβ immunotherapy has been further shown to reverse cognitive decline in transgenic mice (Morgan et al., 2000). In one clinical trial, patients immunized with Aβ peptide who actively generated anti-Aβ antibodies showed a significantly slower rate of decline in cognitive functions (Hock et al., 2003). However, a study which followed AN1792 immunized subjects for six years following the Elan clinical trial showed no evidence of improved survival or of an improvement in the time to severe dementia in the AN1792 group versus the placebo group (Holmes et al., 2008).
Companies:	Genentech, Inc.
Notes:	For clinical trials of MABT5102A on clinicaltrials.gov see MABT5102A. In 2012 it was announced that Crenezumab was selected for use in the Alzheimer's Prevention Initiative study, the first-ever therapeutic prevention trial in cognitively healthy people. For more information, see Alzforum news story. This entry was updated September 1, 2012.

References

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