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[masterlongevity]

#alzheimer $biib #abeta #aducanumab #gantenerumab #ADPD

Abstract: 045
A COMPARATIVE STUDY OF BINDING PROPERTIES OF GANTENERUMAB AND ADUCANUMAB ANALOG TO AGGREGATED AMYLOID-BETA
Aims

Different types of anti-Abeta monoclonal antibodies are being developed as potential disease modifying treatments for AD. Antibodies that recognize and clear aggregated forms of amyloid plaques and oligomers are predicted to confer clinical benefit, as recently demonstrated in a proof of concept study of aducanumab. Gantenerumab is a fully human dual epitope specific antibody with high affinity for aggregated amyloid-beta. We evaluated the binding of gantenerumab and an aducanumab analog to synthetic amyloid-beta in-vitro and to parenchymal and vascular amyloid deposits, ex-vivo and in-vivo.
Method

Gantenerumab and aducanumab analog were expressed in a human IgG1 format. Ex-vivo binding to human parenchymal and vascular amyloid-beta deposits was assessed by immune-fluorescence and quantitative image analysis on AD brain sections ex vivo. Similarly, target engagement in vivo was investigated in PS2APP mice at single doses. In-vitro binding to synthetic amyloid-beta monomers, oligomers and fibrils was measured by Biacore and immunoassays.
Results

Both antibodies bind to human amyloid deposits in an effective and comparable manner in-vivo (PS2APP mice) and ex-vivo (human AD brain). No obvious difference in binding to parenchymal plaques or vascular amyloid deposits was observed. In vitro binding properties to synthetic amyloid-beta species will be presented.
Conclusion

Gantenerumab and the aducanumab analog bind oligomeric and fibrillar forms of amyloid-beta. Preferential binding to parenchymal over vascular amyloid was not observed for either antibody. These data suggest that both antibodies are equally effective at binding and clearing aggregated forms of amyloid-beta.