Analysis of autoantibodies for targeting pathogenesis and therapyof misfolding diseases

2012 Fiscal Year Final Research Report

• Project/Area Number: 23659303
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Laboratory medicine
• Research Institution: Kumamoto University
• Principal Investigator: ANDO Yukio 熊本大学, 大学院・生命科学研究部, 教授 (20253742)
• Co-Investigator(Kenkyū-buntansha): OBAYASHI Konen 熊本大学, 医学部附属病院, 特任教授 (90361899) ; JONO Hirofumi 熊本大学, 医学部附属病院, 准教授 (40515483)
• Project Period (FY): 2011 – 2012
• Keywords: ミスフォールディング病 / トランスサイレチン / アミロイドーシス / ミスフォールディング / 自己抗体 / エピトープ / 家族性アミロイドポリニューロパチー / 遺伝子変異

Research Abstract

We examined presence or absence of anti-variant transthyretin (TTR) antibody in both transgenic rats and familial amyloidotic polyneuropathy (FAP ATTR V30M). In significant numbers of Japanese and Swedish FAP patients, the antibody was present. All patients were late onset cases. As epitopes of TTR variant, ATTR24-35, and 105-115 were listed. When we consider the novel therapy for FAP, this findings are very important and give some hint for the essential therapy.

Research Products

• [Journal Article] Guideline oftransthyretin-related hereditaryamyloidosis for clinicians (2013)
  • Author(s): Ando Y, Coelho T, Berk JL, Cruz MW,Ericzon BG, Ikeda S, Lewis WD, Obici L,Plante-Bordeneuve V, Rapezzi C, Said G,Salvi F
  • Journal Title: Orphanet JRare Dis Volume: 8 Pages: 31
  • DOI: DOI:10.1186/1750-1172-8-3
  • Peer Reviewed
• [Journal Article] Impact of antibodies againstamyloidogenic transthyretin (ATTR) onphenotypes of patients with familialamyloidotic polyneuropathy (FAP) ATTRValine30Methionine (2013)
  • Author(s): Obayashi K, Tasaki M, Jono H, Ueda M,Shinriki S, Misumi Y, Yamashita T, OshimaT, Nakamura T, Ikemizu S, Anan I, Suhr O,Ando Y
  • Journal Title: Clin Chim Acta Volume: 419 Pages: 127-31
  • DOI: DOI:10.1016/j.cca.2013.02.002
  • Peer Reviewed
• [Journal Article] Current state of dominotransplantation in Japan in terms ofsurgical procedures and de novo amyloidneuropathy (2012)
  • Author(s): Asonuma K, Ohya Y, Isono K, TakeichiT, Yamamoto H, Lee KJ, Okumura K, Ando Y,Inomata Y
  • Journal Title: Amyloid Volume: 19 Suppl 1 Pages: 75-77
  • DOI: DOI: 10.3109/13506129.2012.674582
  • Peer Reviewed
• [Journal Article] Familial Amyloidosis Consortium.The Diflunisal Trial: study accrual anddrug tolerance (2012)
  • Author(s): Berk JL, Suhr OB, Sekijima Y,Yamashita T, Heneghan M, Zeldenrust SR,Ando Y, Ikeda S, Gorevic P, Merlini G,Kelly JW, Skinner M, Bisbee AB, Dyck PJ,Obici L
  • Journal Title: Amyloid Volume: 19 Suppl 1 Pages: 37-38
  • DOI: DOI: 10.3109/13506129.2012.678509
  • Peer Reviewed
• [Journal Article] Potential use of lactosylateddendrimer (G3)/α-cyclodextrinconjugates as hepatocyte-specific siRNAcarriers for the treatment of familialamyloidotic polyneuropathy (2012)
  • Author(s): Hayashi Y, Mori Y, Yamashita S,Motoyama K, Higashi T, Jono H, Ando Y,Arima H
  • Journal Title: Mol Pharm Volume: 9 Pages: 1645-1653
  • DOI: DOI:10.1021/mp200654g
  • Peer Reviewed
• [Journal Article] Systemicdelivery of transthyretin siRNA mediatedby lactosylateddendrimer/α-cyclodextrin conjugatesinto hepatocyte for familial amyloidoticpolyneuropathy therapy (2012)
  • Author(s): Hayashi Y, Mori Y, Higashi T, MotoyamaK, Jono H, Sah DW, Ando Y, Arima H
  • Journal Title: Amyloid Volume: 19 Suppl 1 Pages: 47-49
  • DOI: DOI:10.3109/13506129.2012.674581
  • Peer Reviewed
• [Journal Article] Potential use ofglucuronylglucosyl-β-cyclodextrin as anovel therapeutic tool for familialamyloidotic polyneuropathy (2012)
  • Author(s): Jono H, Anno T, Motoyama K, Misumi Y,Tasaki M, Oshima T, Mori Y, Mizuguchi M,Ueda M, Shinriki S, Shono M, Obayashi K,Arima H, Ando Y
  • Journal Title: Amyloid Volume: 19 Suppl 1 Pages: 50-52
  • DOI: DOI:10.3109/13506129
  • Peer Reviewed
• [Journal Article] Interaction betweenamyloid fibril formation andextracellular matrix in the proceedings ofVIIIth International Symposium onFamilial Amyloidotic Polyneuropathy (2012)
  • Author(s): Misumi Y, Ueda M, Obayashi K, Jono H,Yamashita T, Ando Y
  • Journal Title: Amyloid Volume: 19 Suppl 1 Pages: 8-10
  • DOI: DOI:10.3109/13506129.2012.674987
  • Peer Reviewed
• [Journal Article] Capillaryelectrophoretic profile ofβ2-microglobulin intermediateassociated with hemodialysis (2012)
  • Author(s): Motomiya Y, Uji Y, Ando Y
  • Journal Title: Ther ApherDial Volume: 16 Pages: 350-354
  • DOI: DOI:10.1111/j.1744-9987.2012.01069.x.
  • Peer Reviewed
• [Journal Article] Focus on autonomicdysfunction in familial amyloidotic polyneuropathy (FAP) (2012)
  • Author(s): Obayashi K, Ando Y
  • Journal Title: Amyloid Volume: 9 Suppl 1 Pages: 28-29
  • DOI: DOI:10.3109/13506129.2012.673514.
  • Peer Reviewed
• [Journal Article] The occurrence of isletamyloid polypeptide amyloidosis inJapanese subjects (2012)
  • Author(s): Su Y, Misumi Y, Ueda M, Shono M, TasakiM, Jono H, Obayashi K, Senokuchi T,Yamagata K, Ando Y
  • Journal Title: Pancreas Volume: 41 Pages: 971-973
  • DOI: DOI: 10.1097/MPA.0b013e318249926a
  • Peer Reviewed
• [Journal Article] Antibodytherapy for familial amyloidoticpolyneuropathy (2012)
  • Author(s): Su Y, Jono H, Torikai M, Hosoi A,Soejima K, Guo J, Tasaki M, Misumi Y, UedaM, Shinriki S, Shono M, Obayashi K,Nakashima T, Sugawara K, Ando Y
  • Journal Title: Amyloid Volume: 19 Suppl 1 Pages: 45-46
  • DOI: DOI: 10.3109/13506129.2012.674075
  • Peer Reviewed
• [Journal Article] Novel function of transthyretin inpancreatic alpha cells (2012)
  • Author(s): Su Y, Jono H, Misumi Y, Senokuchi T,Guo J, Ueda M, Shinriki S, Tasaki M, ShonoM, Obayashi K, Yamagata K, Araki E, AndoY
  • Journal Title: FEBS Lett Volume: 586 Pages: 215-22
  • DOI: DOI:10.1016/j.febslet.2012.10.025
  • Peer Reviewed
• [Journal Article] Effect ofHeparin on Conformation of the β(2)-Microglobulin Molecule (2012)
  • Author(s): Uji Y, Motomiya Y, Ando Y
  • Journal Title: Ther Apher Dial Volume: 16 Pages: 159-162
  • DOI: DOI:10.1111/j.1744-9987.2011.01039.x
  • Peer Reviewed
• [Journal Article] Aged vervet monkeys developingtransthyretin amyloidosis with the humandisease-causing Ile122 allele: A validpathological model of the human disease (2012)
  • Author(s): Ueda M, Ageyama N, Nakamura S,Nakamura M, Chambers J, Misumi Y,Mizuguchi M, Shinriki S, Kawahara S,Tasaki M, Jono H, Obayashi K, Sasaki E, UneY, Ando Y
  • Journal Title: Lab Invest Volume: 92 Pages: 474-484
  • DOI: DOI:10.1038/labinvest.2011.195.
  • Peer Reviewed
• [Journal Article] Long-term survival after livertransplantation in patients with familialamyloid polyneuropathy (2012)
  • Author(s): Yamashita T, Ando Y, Okamoto S, MisumiY, Hirahara T, Ueda M, Obayashi K, NakamuraM, Jono H, Shono M, Asonuma K, Inomata Y,Uchino M
  • Journal Title: Neurology Volume: 78 Pages: 637-643
  • DOI: DOI:10.1212/WNL.0b013e318248df18
  • Peer Reviewed
• [Journal Article] 最新の神経難病治療と今後の展望: アミロイドーシス (2012)
  • Author(s): 植田光晴、安東由喜雄
  • Journal Title: 医薬ジャーナル Volume: 48 Pages: 1307-1314
• [Journal Article] 熊本大学医学部附属病院で新たにスタートしたアミロイドーシス診療体制構築事業 (2012)
  • Author(s): 大林光念
  • Journal Title: Schnellar Volume: 83 Pages: 3-7
• [Journal Article] C 線維の機能評価に Aδ特異的痛覚閾値検査を組み合わせた小径線維ニューロパチーの早期診断 (2012)
  • Author(s): 大林光念、大嶋俊範、山下太郎、安東由喜雄
  • Journal Title: 末梢神経 Volume: 23 Pages: 321-322
  • Peer Reviewed
• [Journal Article] 家族性アミロイドポリニューロパチーにおける臨床症候に対する肝移植の長期的効果の検討 (2012)
  • Author(s): 山下太郎,奥村幸祐,大嶋俊範,三隅洋平,植田明彦,菅智宏,神力悟,植田光晴,城野博史,大林光念,山下賢,前田寧,安東由喜雄
  • Journal Title: 末梢神経 Volume: 23 Pages: 256-257
  • Peer Reviewed
• [Journal Article] A report on VIIIthinternational symposium on familialamyloidotic polyneuropathy and VIIthinternational symposium on livertransplantation in familial amyloidoticpolyneuropathy (2012)
  • Author(s): Ando Y
  • Journal Title: Amyloid Volume: 19 Suppl 1 Pages: 1-2
  • DOI: DOI: 10.3109/13506129.2012.673513
  • Peer Reviewed
• [Journal Article] Ueda M. Diagnostics andtherapeutic approaches to transthyretinamloidosis (2012)
  • Author(s): Ando Y
  • Journal Title: Curr Med Chem Volume: 19 Pages: 2312-2323
  • DOI: DOI: 10.3109/13506129
• [Journal Article] 学際的連携がひらく末梢神経機能再建への展望 - 家族性アミロイドポリニューロパチーの末梢神経障害と治療 (2012)
  • Author(s): 安東由喜雄
  • Journal Title: 末梢神経 Volume: 23 Pages: 180-187
  • Peer Reviewed
• [Journal Article] 家族性アミロイドポリニューロパチー(FAP)に対する肝移植の有用性と限界 (2012)
  • Author(s): 安東由喜雄
  • Journal Title: 臨床神経学 Volume: 51 Pages: 1138-1140
  • Peer Reviewed
• [Journal Article] アミロイドーシス (2012)
  • Author(s): 安東由喜雄
  • Journal Title: 医薬ジャーナル Volume: 48 Pages: 91-98
• [Journal Article] 臨床化学からみたアミロイドーシス (2012)
  • Author(s): 大林光念, 安東由喜雄
  • Journal Title: 臨床化学 Volume: 41 Pages: 4
  • Peer Reviewed
• [Journal Article] 質量分析法を用いた新たなアミロイドーシスの診断法 (2012)
  • Author(s): 田崎義雅, 安東由喜雄
  • Journal Title: 臨床化学 Volume: 41 Pages: 41-46
  • Peer Reviewed
• [Presentation] Familial amyloidoticpolyneuropathy in Japan (2013)
  • Author(s): Ando Y
  • Organizer: Alnylam Meeting
  • Place of Presentation: Alnylam Pharmaceutical,U.S.A
  • Year and Date: 2013-03-01
• [Presentation] 専門性、地域性を生かした検査部の新しい試み: アミロイドーシス診療体制構築事業 (2012)
  • Author(s): 大林光念、田崎雅義、神力悟、宇宿弘輝、池田勝義、安東由喜雄
  • Organizer: 59回日本臨床検査医学会年次学術集会
  • Place of Presentation: 京都国際会議場、京都
  • Year and Date: 20121129-1202
• [Presentation] あなたならどうする自律神経障害の臨床: 家族性アミロイドポリニューロパチー(FAP) と自律神経障害 (2012)
  • Author(s): 安東由喜雄
  • Organizer: 第65回日本自律神経学会総会
  • Place of Presentation: 都市センターホテル、東京
  • Year and Date: 20121025-1026
• [Presentation] 全身性アミロイドーシスの診断と自律神障害 (2012)
  • Author(s): 大林光念、山下太郎、大嶋俊範、安東由喜雄
  • Organizer: 第65回日本自律神経学会総会
  • Place of Presentation: 都市センターホテル、東京
  • Year and Date: 20121025-1026
• [Presentation] Early TTR-FAPpatient identification and diagnosis - theexample of Japan (2012)
  • Author(s): Yamashita T, Ando Y
  • Organizer: TTR-FAP GlobalCommercial Advisory Board
  • Place of Presentation: London, UK
  • Year and Date: 20121018-1019
• [Presentation] 家族性アミロイドポリニューロパチー患者における異型トランスサイレチンに対する自己抗体の存在とその意義 (2012)
  • Author(s): 大林光念、田崎雅義、神力悟、植田光晴、城野博史、安東由喜雄
  • Organizer: 第52回日本臨床化学会年次集会
  • Place of Presentation: いわて県民情報交流センター、盛岡
  • Year and Date: 20120906-0908
• [Presentation] New therapetic approaches forfamilial amyloidotic polyneurotahy (2012)
  • Author(s): Ando Y
  • Organizer: XIII International Symposium onAmyloidosis
  • Place of Presentation: Groningen,The Netherland
  • Year and Date: 20120506-0510
• [Presentation] Detection of autoantibodiesagainst ATTR in patients with FAP ATTR V30M (2012)
  • Author(s): Obayashi K
  • Organizer: XIIth International Symposium onAmyloidosis
  • Place of Presentation: Groningen,The Netherland
  • Year and Date: 20120506-0510
• [Presentation] シクロデキストリンの包接特性を活用した家族性アミロイドポリニューロパチーの新規治療薬の開発 (2012)
  • Author(s): 城野博史、安野貴幸、本山敬一、三隅洋平、田崎雅義、大嶋俊範、森由匡、水口峰之、植田光晴、神力悟、庄野信、大林光念、有馬英俊、安東由喜雄
  • Organizer: 日本薬学会第132 年会
  • Place of Presentation: 北海道大学、札幌
  • Year and Date: 20120328-0331
• [Presentation] Mass spectrometry as a usefuldiagnostic tool for hereditaryamyloidosis (2012)
  • Author(s): Ando Y
  • Organizer: 19th International massspectrometry conference
  • Place of Presentation: ICCKyoto,Kyoto, Japan
  • Year and Date: 2012-12-01
• [Presentation] 学際的連携がひらく末梢神経機能再建への展望, アミロイドニューロパチーの病態解析と神経障害 (2012)
  • Author(s): 安東由喜雄
  • Organizer: 第23回日本末梢神経学会
  • Place of Presentation: 九州大学医学部百年講堂、福岡
  • Year and Date: 2012-08-30
• [Presentation] 神経疾患の疼痛, 家族性アミロイドポリニューロパチーの疼痛について (2012)
  • Author(s): 安東由喜雄
  • Organizer: 第34回日本疼痛学会
  • Place of Presentation: 熊本国際交流会館、熊本
  • Year and Date: 2012-07-20
• [Book] 標準臨床検査医学 (2013)
  • Author(s): 安東由喜雄
  • Total Pages: 456
  • Publisher: 医学書院
• [Book] 先天性代謝異常ハンドブッ ク (2013)
  • Author(s): 安東由喜雄
  • Total Pages: 456
  • Publisher: 中山書店
• [Book] 今日の神経疾患治療指針第2 版 (2013)
  • Author(s): 安東由喜雄
  • Total Pages: 1136
  • Publisher: 医学書院