title: Novel Antibody for the Treatment of Transthyretin Amyloidosis.
abstract: Familial amyloidotic polyneuropathy (FAP) is a systemic amyloidosis mainly caused by amyloidogenic transthyretin (ATTR). This incurable disease causes death ∼10 years after onset. Although it has been widely accepted that conformational change of the monomeric form of transthyretin (TTR) is very important for amyloid formation and deposition in the organs, no effective therapy targeting this step is available. In this study, we generated a mouse monoclonal antibody, T24, that recognized the cryptic epitope of conformationally changed TTR. T24 inhibited TTR accumulation in FAP model rats, which expressed human ATTR V30M in various tissues and exhibited non-fibrillar deposits of ATTR in the gastrointestinal tracts. Additionally, humanized T24 (RT24) inhibited TTR fibrillation and promoted macrophage phagocytosis of aggregated TTR. This antibody did not recognize normal serum TTR functioning properly in the blood. These results demonstrate that RT24 would be an effective novel therapeutic antibody for FAP.
authors.affiliation: From the Chemo-Sero-Therapeutic Research Institute (KAKETSUKEN), 1314-1 Kyokushi Kawabe Kikuchi Kumamoto, 869-1298.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Hosoi
authors.affiliation: the Departments of Neurology and.
authors.forename: Yu
authors.initials: Y
authors.lastname: Su
authors.affiliation: From the Chemo-Sero-Therapeutic Research Institute (KAKETSUKEN), 1314-1 Kyokushi Kawabe Kikuchi Kumamoto, 869-1298.
authors.forename: Masaharu
authors.initials: M
authors.lastname: Torikai
authors.affiliation: the Department of Clinical Pharmaceutical Sciences, Graduate School of Pharmaceutical Sciences, Kumamoto University, and.|the Department of Pharmacy, Kumamoto University Hospital, 1-1-1 Honjo, Chuo-ku, Kumamoto 860-8556, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Jono
authors.affiliation: From the Chemo-Sero-Therapeutic Research Institute (KAKETSUKEN), 1314-1 Kyokushi Kawabe Kikuchi Kumamoto, 869-1298.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Ishikawa
authors.affiliation: From the Chemo-Sero-Therapeutic Research Institute (KAKETSUKEN), 1314-1 Kyokushi Kawabe Kikuchi Kumamoto, 869-1298.
authors.forename: Kenji
authors.initials: K
authors.lastname: Soejima
authors.affiliation: From the Chemo-Sero-Therapeutic Research Institute (KAKETSUKEN), 1314-1 Kyokushi Kawabe Kikuchi Kumamoto, 869-1298.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Higuchi
authors.affiliation: the Departments of Neurology and.
authors.forename: Jianying
authors.initials: J
authors.lastname: Guo
authors.affiliation: the Departments of Neurology and.
authors.forename: Mitsuharu
authors.initials: M
authors.lastname: Ueda
authors.affiliation: the Departments of Neurology and.
authors.forename: Genki
authors.initials: G
authors.lastname: Suenaga
authors.affiliation: the Departments of Neurology and.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Motokawa
authors.affiliation: Immunogenetics, Graduate School of Medical Sciences, and.
authors.forename: Tokunori
authors.initials: T
authors.lastname: Ikeda
authors.affiliation: Immunogenetics, Graduate School of Medical Sciences, and.
authors.forename: Satoru
authors.initials: S
authors.lastname: Senju
authors.affiliation: From the Chemo-Sero-Therapeutic Research Institute (KAKETSUKEN), 1314-1 Kyokushi Kawabe Kikuchi Kumamoto, 869-1298, nakashima-to@kaketsuken.or.jp.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Nakashima
authors.affiliation: the Departments of Neurology and andoy709@kumamoto-u.ac.jp.
authors.forename: Yukio
authors.initials: Y
authors.lastname: Ando
mesh_terms: D028227:Amyloid Neuropathies, Familial / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D000818:Animals; D058846:Antibodies, Monoclonal, Murine-Derived / Q000276:immunology* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008264:Macrophages / Q000276:immunology* / Q000473:pathology; D008297:Male; D051379:Mice; D010587:Phagocytosis / Q000187:drug effects*; D011228:Prealbumin / Q000276:immunology*; D051381:Rats
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D011228:Prealbumin
keywords: FAP; amyloid; antibody; antibody engineering; drug design; fibril; transthyretin