Publication Abstract from PubMed
Alzheimer's disease is the most common form of dementia, affecting 26 million people worldwide. The Abeta peptide (39-43 amino acids) derived from the proteolytic cleavage of the amyloid precursor protein is one of the main constituents of amyloid plaques associated with disease pathogenesis and therefore a validated target for therapy. Recently, we characterized antibody fragments (Fab and scFvs) derived from the murine monoclonal antibody WO-2, which bind the immunodominant epitope ((3)EFRH(6)) in the Abeta peptide at the N-terminus. In vitro, these fragments are able to inhibit fibril formation, disaggregate preformed amyloid fibrils, and protect neuroblastoma cells against oligomer-mediated toxicity. In this study, we describe the humanization of WO-2 using complementary determining region loop grafting onto the human germline gene and the determination of the three-dimensional structure by X-ray crystallography. This humanized version retains a high affinity for the Abeta peptide and therefore is a potential candidate for passive immunotherapy of Alzheimer's disease.
Germline humanization of a murine Abeta antibody and crystal structure of the humanized recombinant Fab fragment.,Robert R, Streltsov VA, Newman J, Pearce LA, Wark KL, Dolezal O Protein Sci. 2010 Feb;19(2):299-308. PMID:20014445[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
