Generation and brain delivery of anti-aggregating antibodies against beta-amyloid plaques using phage display technology.
Antibodies towards the N-terminal region of the beta-amyloid peptide bind to beta-amyloid fibrils, leading to their disaggregation. We generated anti-aggregating beta-amyloid antibodies using filamentous phages displaying the only four amino acids EFRH found to be the main regulatory site for beta-amyloid formation. In order to overcome the low permeability of the blood brain barrier for targeting 'anti-aggregating' mAbs to the betaA plaques in the brain, we applied antibody engineering methods to minimize the size of the mAbs while maintaining their biological activity. We found that single-chain antibodies displayed on the surface of the phage are capable of entering the central nervous system (CNS). The feasibility of these novel strategies for the production and targeting of anti-aggregating antibodies against beta-amyloid plaques to disease affected regions in the CNS may have clinical potential for treatment of Alzheimer's disease.
Solomon
B
B
Department of Molecular Microbiology and Biotechnology, Faculty of Life Sciences, Tel Aviv University, Israel. beka@ccsg.tau.ac.il
Frenkel
D
D
D000544:Alzheimer Disease / Q000378:metabolism / Q000628:therapy; D016229:Amyloid beta-Peptides / Q000276:immunology* / Q000378:metabolism; D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics*; D001812:Blood-Brain Barrier; D006168:Guinea Pigs; D007167:Immunotherapy; D051379:Mice; D019151:Peptide Library; D011817:Rabbits
D016229:Amyloid beta-Peptides; D000911:Antibodies, Monoclonal; D019151:Peptide Library