2010 Fiscal Year Final Research Report
New therapeutic strategies to ameliorate senile systemic amyloidosis by native state stabilization of TTR protein.
| Project/Area Number |
20590695
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General internal medicine (including Psychosomatic medicine)
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| Research Institution | Shinshu University |
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Principal Investigator |
SEKIJIMA Yoshiki Shinshu University, 医学部附属病院, 准教授 (60322715)
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| Co-Investigator(Kenkyū-buntansha) |
MORITA Hiroshi 信州大学, 医学部附属病院, 准教授 (10262718)
KOYAMA Jun 信州大学, 医学系研究科, 准教授 (10303463)
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| Project Period (FY) |
2008 – 2010
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| Keywords | 老年医学 |
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| Research Abstract |
Firstly, we measured the frequency of unrecognised wild-type TTR deposition in idiopathic CTS patients. Thirty-four (34%) of 100 patients with idiopathic CTS showed amyloid deposition in the tenosynovial tissue, and all amyloid showed specific immunolabelling with anti-TTR antibody. Direct DNA sequencing of the entire TTR gene did not reveal any mutations, indicating that all amyloid deposits were derived form wild-type TTR. Statistical analysis using logistic regression showed that the prevalence of TTR deposition in the idiopathic CTS group was significantly higher than that in controls, and age and male gender were independent risk factors for TTR amyloid deposition.
Secondly, we screened already approved prescription drugs and selected diflunisal as a candidate drug for clinical trial, because its high serum concentration after oral administration leads to high TTR binding stoichiometry. We investigated the efficacy and safety of administration of diflunisal to SSA patients. Orally administered diflunisal significantly increased serum TTR concentration and stabilized TTR tetramer structure in each patient. Long-term randomized controlled trial is necessary to determine the clinical effects of diflunisal on SSA.
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[Journal Article] SELDI-TOF MS evaluation of variant transthyretins for diagnosis and pathogenesis of familial amyloidotic polyneuropathy.2009
Author(s)
Ueda M, Misumi Y, Mizuguchi M, Nakamura M, Yamashita T, Sekijima Y, Ota K, Shinriki S, Jono H, Ikeda SI, Suhr OB, Ando Y.
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Journal Title
Clin Chem 55
Pages: 1223-1227
Peer Reviewed
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