title: Antibody therapy for familial amyloidotic polyneuropathy.
abstract: Although it is believed that altered conformations exposing cryptic regions are intermediary and critical steps in the mechanism of transthyretin (TTR) amyloid formation, no effective therapy targeting this step is available. In this study, to establish the antibody therapy for familial amyloidotic polyneuropathy (FAP), we generated a monoclonal anti-TTR antibody, which specifically reacts with surface epitopes of TTR (MAb ATTR) and evaluated its binding affinity and specificity for TTR amyloid fibrils. MAb ATTR showed specific binding affinity for TTR amyloid fibrils, but not for native form of TTR. Moreover, MAb ATTR indeed showed the high consistency with Congo red positive areas in tissue specimens from FAP ATTR V30M patients, indicating that MAb ATTR showed binding affinity and specificity for TTR amyloid fibrils in vitro and in vivo. MAb ATTR may have a potential to suppress TTR amyloid deposition and become a candidate for the antibody therapy for FAP.
authors.affiliation: Department of Diagnostic Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan. syag_2006@hotmail.com
authors.forename: Yu
authors.initials: Y
authors.lastname: Su
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Jono
authors.forename: Masaharu
authors.initials: M
authors.lastname: Torikai
authors.forename: Akihiko
authors.initials: A
authors.lastname: Hosoi
authors.forename: Kenji
authors.initials: K
authors.lastname: Soejima
authors.forename: Jianying
authors.initials: J
authors.lastname: Guo
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Tasaki
authors.forename: Yohei
authors.initials: Y
authors.lastname: Misumi
authors.forename: Mitsuharu
authors.initials: M
authors.lastname: Ueda
authors.forename: Satoru
authors.initials: S
authors.lastname: Shinriki
authors.forename: Makoto
authors.initials: M
authors.lastname: Shono
authors.forename: Konen
authors.initials: K
authors.lastname: Obayashi
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Nakashima
authors.forename: Keishin
authors.initials: K
authors.lastname: Sugawara
authors.forename: Yukio
authors.initials: Y
authors.lastname: Ando
mesh_terms: D028227:Amyloid Neuropathies, Familial / Q000188:drug therapy / Q000378:metabolism*; D000911:Antibodies, Monoclonal / Q000378:metabolism* / Q000627:therapeutic use*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D007668:Kidney / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D011228:Prealbumin / Q000378:metabolism*; D013961:Thyroid Gland / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D011228:Prealbumin