Gene therapy for familial amybidotic polyneuropathy by urtra-fundaoning artificial nucleic acids

• Project/Area Number: 15390275
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Neurology
• Research Institution: Kumamoto University
• Principal Investigator: ANDO Yukio Kumamoto University, Graduate School of Medical Sciences, 大学院・医学薬学研究部, 講師 (20253742)
• Co-Investigator(Kenkyū-buntansha): NAKAMURA Masaaki Kumamoto University Hospital, Resident, 医学部附属病院, 医員 ; IMANISHI Takeshi Kumamoto University, Graduate School and School of Pharmaceutical Sciences, 薬学研究科, 教授 (40028866)
• Project Period (FY): 2003 – 2004
• Project Status: Completed (Fiscal Year 2004)
• Budget Amount: ¥11,700,000 (Direct Cost: ¥11,700,000); Fiscal Year 2004: ¥3,400,000 (Direct Cost: ¥3,400,000); Fiscal Year 2003: ¥8,300,000 (Direct Cost: ¥8,300,000)
• Keywords: Familial amyloidotic polyneuropathy / Transthyretin / Amyloidosis / Environmental factor / trance metals / Haplotype / Sweden / Neuropathy / ニューロパチー / 家族性アミロイドニューロパチー / 遺伝子治療 / single-stranded oligonucleotides (SSOs) / トランスサイレチン(TTR) / 遺伝子修復関連遺伝子 / マイクロアレイ

Research Abstract

It is well known that the phenotype of Swedish FAP patients is quite different from that in other countries' FAP patients. To elucidate the reason, we performed the following studies. 1.Fact-finding study in northern part of Sweden : totally 8 medical doctors, such as neurologists and ophthalmologists went to northern part of Sweden to check clinical manifestations of the patients and way of living. 2.Trace metal study : Water in pond, river well, and water from water pipes were collected to measure 12 metals in water. 3.Haplotype study : Haplotypes of Swedish FAP patients were compared with those in other countries' FAP patients.
By the studies, of metals in water, As concentrations were extremely higher compared with those in Japanese samples. In this project in next year, effect of As on amyloid formation in vitro will be examined in our amyloid formation assay system. Concerning clinical manifestations, as we expected, most of the patients was late-onset, and clinical manifestations were very mild. In the haplotype study, Swedish FAP patient samples showed different haplotypes in several genes compared with those in Japanese, Portugal, and Spanish FAP patients, suggesting that inaddition to the effect by environmental factors, the difference of the genetic background may partially explain the phenotype difference.
In these points we continue our research projects in the next year.

Research Products

• [Journal Article] Studies on unfolded beta2-microglobulin at C-terminal in dialysis related amyloidosis (2005)
  • Author(s): Motomiya Y, Ando Y, Haraoka K, Sun X, Morita H, Amano I, Uchimura T, Maruyama I
  • Journal Title: Kidney Int 67 Pages: 314-320
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Lactoferrin Glu561Asp Facilitates Amyloid Formation in the Cornea. (2005)
  • Author(s): Araki-Sasaki K, Ando Y, Nakamura M, Kitagawa K, Ikemizu S, Kawaji T, Yamashita T, Ueda M, Hirano K, Yamada M, Matsumoto K, Kinoshita S, Tanihara H.
  • Journal Title: Brit J Ophthal (in press)
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Common origin of the Val30Met mutation responsible for the amyloidogenic transthyretin type of familial amyloidotic polyneuropathy. (2004)
  • Author(s): Ohmori H, Ando Y.他
  • Journal Title: J Med Genet 41
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Targeted conversion of the transthyretin gene in vitro and in vivo. (2004)
  • Author(s): Nakamura M, Ando Y.他
  • Journal Title: Gene Ther 11 Pages: 838-846
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Pathology of early- vs late-onset TTR Met30 familial amyloid polyneuropathy. (2004)
  • Author(s): Koike H et al.(Ando Y 9^<th>)
  • Journal Title: Neurology 63 Pages: 129-138
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] A different amyloid formation mechanism : De novo oculoleptomeningeal amyloid deposits after liver transplantation (2004)
  • Author(s): Ando Y et al.
  • Journal Title: Transplantation 77 Pages: 345-349
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Near-infrared spectrophotoscopy in assessment of autonomic dysfunction. -As a useful marker of autonomic dysfunction- (2004)
  • Author(s): Obayashi K, Ando Y et al.
  • Journal Title: Neurology 63 Pages: 164-166
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Familial amyloid angiopathy with muscular amyloid angiopathy. (2004)
  • Author(s): Yamashita T, Ando Y, et al.
  • Journal Title: Muscle Nerve 31 Pages: 41-45
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Targeted conversion of the transthyretin gene in vitro and in vivo (2004)
  • Author(s): Nakamura M, Ando Y, Nagahara S, Sano A, Ochiya T, Maeda S, Kawaji T, Ogawa M, Hirata A, Terazaki H, Haraoka K, Tanihara H, Uchino M, Yamamura K
  • Journal Title: Gene Ther 11 Pages: 838-846
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Common origin of the Val30Met mutation responsible for the amyloidogenic transthyretin type of familial amyloidotic polyneuropathy (2004)
  • Author(s): Ohmori H, Ando Y, Makita Y, Onouchi Y, Nakajima T, Saraiva M J M, Terazaki H, Suhr O, Sobue G, Nakamura M, Yamaizumi M, Munar-Ques M, Inoue I, Uchino M, Hata A
  • Journal Title: J Med Genet 41
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Pathology of early-vs late-onset TTR Met30 familial amyloid polyneuropathy (2004)
  • Author(s): Koike H, Misu K, Sugiura M, Iijima M, Mori K, Yamamoto M, Hattori N, Mukai E, Ando Y, Ikeda S, Sobue G
  • Journal Title: Neurology 63 Pages: 129-138
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Near-infrared spectrophotoscopy in assessment of autonomic dysfunction. - As a useful marker of autonomic dysfunction - (2004)
  • Author(s): Obayashi K, Ando Y, Nakamura M, Yamashita T, Ueda M, Haraoka K, Terazaki H, Uchino M
  • Journal Title: Neurology 63 Pages: 164-166
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] A different amyloid formation mechanism : De novo oculoleptomeningeal amyloid deposits after liver transplantation (2004)
  • Author(s): Ando Y, Terazaki H, Nakamura M, Ando E, Haraoka K, Yamashita T, Ueda M, Okabe H, Sasaki Y, Tanihara H, Uchino M, Inomata Y
  • Journal Title: Transplantation 77 Pages: 345-349
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Amyloid imaging probes are useful for detection of prion plaques and treatment of transmissible spongiform encephalopathies. (2004)
  • Author(s): Ishikawa K., Doh-ura K, Kudo Y, Nishida N, Murakami-Kubo I, Ando Y, Sawada T, Iwaki T
  • Journal Title: J Gen Virol 85 Pages: 1785-1790
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Inhibitory effect of α-tocopherol on methylmercury-induced oxidative stress. (2004)
  • Author(s): Yamashita T, Ando Y, Nakamura M, Obayashi K, Terazaki H, Haraoka K, Sun X, Ueda M, Uchino M.
  • Journal Title: Environ Health Prev Med 9 Pages: 111-117
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Familial amyloid polyneuropathy : Hypertrophy of ligaments supporting the spinal cord. (2004)
  • Author(s): Kitajima M, Horogi Y, Yamura K, Ikushima I, Hayashida Y, Ando Y, Uchino M, Yamashita Y.
  • Journal Title: Am J Neuroradiol 25 Pages: 1599-1602
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Familial amyloid angiopathy with muscular amyloid angiopathy. (2004)
  • Author(s): Yamashita T, Ando Y, Katsuragi S, Nakamura M, Obayashi K, Haraoka K, Ueda M, Uchino M
  • Journal Title: Muscle Nerve 31 Pages: 41-45
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] A case of vitreous amyloidosis without systemic symptoms in familial amyloidotic Polyneuropathy (2004)
  • Author(s): Kawaji T, Ando Y, Ando E, Nakamura M, Hirata K, Tanihara H
  • Journal Title: Amyloid 11 Pages: 257-259
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Application of gene therapy for FAP. (2004)
  • Author(s): Nakamura M, Ando Y
  • Journal Title: Expert Opin Ther Pat 10 Pages: 1621-1627
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Circadian rhythm of protein C in human plasma : Useful marker of autonomic function in liver (2004)
  • Author(s): Obayashi K, Hanyu O, Miida T, Ando Y, Nakamura M, Zhu Y, Okada M.
  • Journal Title: Clin Auton Res 5(in press)
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Common origin of the Val30Met mutation responsible for the amyloidogenic transthyretin type of familial amyloidotic polyneuropathy. (2004)
  • Author(s): Ohmori H, Ando Y. 他
  • Journal Title: J Med Genet 41・4
• [Journal Article] Targeted conversion of the transthyretin gene in vitro and in vivo. (2004)
  • Author(s): Nakamura M, Ando Y. 他
  • Journal Title: Gene Ther 11・10 Pages: 838-846
• [Journal Article] Pathology of early- vs late-onset TTR Met30 familial amyloid polyneuropathy. (2004)
  • Author(s): Koike H et al.(Ando Y 9^<th>)
  • Journal Title: Neurology 63・1 Pages: 129-138
• [Journal Article] A different amyloid formation mechanism : De novo oculoleptomeningeal amyloid deposits after liver (2004)
  • Author(s): Ando Y et al.
  • Journal Title: Transplantation 77・3 Pages: 345-349
• [Journal Article] Near-infrared spectrophotoscopy in assessment of autonomic dysfunction. -As a useful marker of autonomic dysfunction- (2004)
  • Author(s): Obayashi K, Ando Y et al.
  • Journal Title: Neurology 63・1 Pages: 164-166
• [Journal Article] Familial amyloid angiopathy with muscular amyloid angiopathy. (2004)
  • Author(s): Yamashita T, Ando Y, et al.
  • Journal Title: Muscle Nerve 31・1 Pages: 41-45
• [Book] Familial Amyloidotic Polyneuropathy -History and Perspective- (2004)
  • Author(s): Ando Y
  • Total Pages: 87
  • Publisher: Ando Y (Printop Co, Kumamoto)
  • Description: 「研究成果報告書概要(和文)」より
• [Patent(Industrial Property Rights)] アミロイドーシスの予防及び治療のための医療 (2002)
  • Inventor(s): 甲斐 広文, 安東 由喜雄
  • Industrial Property Rights Holder: 甲斐 広文, 安東 由喜雄
  • Filing Date: 2002-05-14
  • Description: 「研究成果報告書概要(和文)」より
• [Patent(Industrial Property Rights)] 部位特異的遺伝子変異促 (2002)
  • Inventor(s): 安東 由喜雄, 中村 政明, 永原 俊治
  • Industrial Property Rights Holder: 安東 由喜雄, 中村 政明
  • Filing Date: 2002-09-20
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Ando Y: "New therapeutic approaches for familial amyloidotic polyneuropathy (FAP)"Amyloid. 10. S55-S67 (2003)
• [Publications] Ando Y, et al.: "A novel tool for detecting amyloid deposits in systemic amyloidosis in vitro and in vivo"Lab Invest. 83. 1751-1759 (2003)
• [Publications] 安東由喜雄: "神経難病の遺伝医療-FAPを中心にして-. 遺伝医療とカウンセリング-その現状と未来-"SOAMT News. 6. 40-51 (2004)
• [Publications] 安東由喜雄: "家族性アミロイドポリニューロパチーの創薬ターゲット分子"医学の歩み. 207. 78-82 (2003)
• [Publications] 安東由喜雄: "遺伝性アミロイドーシスの病態解析と治療"臨床病理. 51. 530-535 (2003)
• [Publications] 安東由喜雄: "遺伝子研究の現段階と臨床への適用のゆくえ"SOAMT News. 7. 1-8 (2004)
• [Publications] Araki S, Ando Y: "Familial amyloidotic polyneuropathy-Progress in Kumamoto, Japan, 1967-2002"Kumamoto Copy Co. 76 (2003)