Development of new diagnostic and surrogate markers for small fiber neuropathy

• Project/Area Number: 15K19184
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Laboratory medicine
• Research Institution: Kumamoto University
• Principal Investigator: Masuda Teruaki 熊本大学, 医学部附属病院, 助教 (50464459)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000); Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2016: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 小径線維ニューロパチー / アミロイドーシス / 早期診断 / 皮膚生検 / トランスサイレチン / 表皮内神経線維密度 / MR-neurography / アミロイド / TTR-FAP / 小径線維 / FAP

Outline of Final Research Achievements

Small fiber neuropathy (SFN) is associated with various diseases, including diabetes and transthyretin-related familial amyloid polyneuropathy (ATTR-FAP). Therefore, early and accurate diagnosis of SFN is becoming increasingly important for the early treatment of ATTR-FAP and diabetic neuropathy. In this study, I investigated which biomarker accurately predicts pathological changes in SFN. The results showed early skin denervation in ATTR-FAP, even in the presymptomatic stage of this disease. Skin denervation was correlated with disease duration and various peripheral neuropathy parameters. Our findings reveal that skin biopsy may be useful for early diagnosis and may serve as a biomarker in clinical trials for SFN.

Research Products

• [Journal Article] Genetic and clinical characteristics of hereditary transthyretin amyloidosis in endemic and non-endemic areas: experience from a single-referral center in Japan. (2018)
  • Author(s): Yamashita T, Ueda M, Misumi Y, Masuda T, Nomura T, Tasaki M, Takamatsu K, Sasada K, Obayashi K, Matsui H, Ando Y.
  • Journal Title: Journal of Neurology Volume: 265 Issue: 1 Pages: 134-140
  • DOI: 10.1007/s00415-017-8640-7
  • Peer Reviewed / Open Access
• [Journal Article] Unwanted road to anemia in transthyretin familial amyloid polyneuropathy may continue irrespective of tafamidis treatment (2018)
  • Author(s): Ikeda T, Masuda T, Ueda M, Yamashita T, Misumi Y, Shinriki S, Ando Y.
  • Journal Title: Annals of Clinical Biochemistry Volume: 印刷中 Issue: 5 Pages: 571-575
  • DOI: 10.1177/0004563218754587
  • Peer Reviewed / Open Access
• [Journal Article] Sushi repeat-containing protein 1: a novel disease-associated molecule in cerebral amyloid angiopathy. (2017)
  • Author(s): Inoue Y, Ueda M, Tasaki M, Takeshima A, Nagatoshi A, Masuda T, Misumi Y, Kosaka T, Nomura T, Mizukami M, Matsumoto S, Yamashita T, Takahashi H, Kakita A, Ando Y.
  • Journal Title: Acta Neuropathologica Volume: 134 Issue: 4 Pages: 605-617
  • DOI: 10.1007/s00401-017-1720-z
  • Peer Reviewed / Open Access
• [Journal Article] Inflammatory state exists in familial amyloid polyneuropathy that may be triggered by mutated transthyretin. (2017)
  • Author(s): Suenaga G, Ikeda T, Masuda T, Motokawa H, Yamashita T, Takamatsu K, Misumi Y, Ueda M, Matsui H, Senju S, Ando Y.
  • Journal Title: Sci. Rep Volume: 7(1) Issue: 1 Pages: 1579-2017
  • DOI: 10.1038/s41598-017-01775-4
  • Peer Reviewed / Open Access
• [Journal Article] Early skin denervation in hereditary and iatrogenic transthyretin amyloid neuropathy. (2017)
  • Author(s): Masuda T, Ueda M, Suenaga G, Misumi Y, Tasaki M, Izaki A, Yanagisawa Y, Inoue Y, Motokawa H, Matsumoto S, Mizukami M, Arimura A, Deguchi T, Nishio Y, Yamashita T, Inomata Y, Obayashi K, Ando Y
  • Journal Title: Neurology Volume: 88 Issue: 23 Pages: 2192-2197
  • DOI: 10.1212/wnl.0000000000004016
  • Peer Reviewed / Open Access
• [Journal Article] Serum amyloid P component: A novel potential player in vessel degeneration in CADASIL. (2017)
  • Author(s): Nagatoshi A, Ueda M, Ueda A, Tasaki M, Inoue Y, Ma Y, Masuda T, Mizukami M, Matsumoto S, Kosaka T, Kawano T, Ito T, Ando Y.
  • Journal Title: Journal of the Neurological Sciences Volume: 379 Pages: 69-76
  • DOI: 10.1016/j.jns.2017.05.033
  • Peer Reviewed
• [Journal Article] A novel transthyretin variant V28S (p.V48S) with a double-nucleotide substitution in the same codon. (2017)
  • Author(s): Okada M, Misumi Y, Ueda M, Yamashita T, Masuda T, Tasaki M, Ando Y.
  • Journal Title: Amyloid Volume: 24 Issue: 4 Pages: 231-232
  • DOI: 10.1080/13506129.2017.1381082
  • Peer Reviewed
• [Journal Article] 肝移植後も緩徐に症候が進行した遺伝性トランスサイレチンアミロイドーシス症例の病理・生化学的検討. (2017)
  • Author(s): 水上 真由美, 植田 光晴, 田崎 雅義, 三隅 洋平, 増田 曜章, 松本 紗也加, 木下 祐美子, 末永 元輝, 大林 光念, 山下 太郎, 安東 由喜雄
  • Journal Title: 末梢神経 Volume: 28 Pages: 101-105
  • Peer Reviewed
• [Journal Article] 皮神経に着目して行う小径線維ニューロパチーの早期診断および病態解析. (2017)
  • Author(s): 増田曜章、大林光念、安東由喜雄
  • Journal Title: 自律神経 Volume: 54 Pages: 230-233
  • Peer Reviewed
• [Journal Article] Novel screening for transthyretin amyloidosis by using fat ultrasonography. (2017)
  • Author(s): Misumi Y, Ueda M, Yamashita T, Masuda T, Kinoshita Y, Tasaki M, Nagase T, Ando Y
  • Journal Title: Ann Neurol Volume: 印刷中 Issue: 4 Pages: 604-608
  • DOI: 10.1002/ana.24914
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Clinicopathological and biochemical findings of thyroid amyloid in hereditary transthyretin amyloidosis with and without liver transplantation. (2017)
  • Author(s): Huang G, Ueda M, Tasaki M, Yamashita T, Misumi Y, Masuda T, Suenaga G, Inoue Y, Kinoshita Y, Matsumoto S, Mizukami M, Tsuda Y, Nomura T, Obayashi K, Ando Y
  • Journal Title: Amyloid Volume: 印刷中 Issue: 1 Pages: 1-6
  • DOI: 10.1080/13506129.2016.1276440
  • Peer Reviewed
• [Journal Article] Early skin denervation in hereditary and iatrogenic transthyretin amyloid neuropathy. (2017)
  • Author(s): Masuda T, Ueda M, Suenaga G, Misumi Y, Tasaki M, Izaki A, Yanagisawa Y, Inoue Y, Motokawa H, Matsumoto S, Mizukami M, Arimura A, Deguchi T, Nishio Y, Yamashita T, Inomata Y, Obayashi K, Ando Y
  • Journal Title: Neurology Volume: in press
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Thomsen disease associated with ptosis and abnormal MR findings (2016)
  • Author(s): Mori Y, Yamashita S, Kato M, Masuda T, Takamatsu K, Kumamoto T, Sasaki R, Ando Y
  • Journal Title: Neuromuscl Disord Volume: 26 Issue: 11 Pages: 805-808
  • DOI: 10.1016/j.nmd.2016.08.016
  • Peer Reviewed
• [Journal Article] Hereditary amyloidosis with cardiomyopathy caused by the novel variant transthyretin A36D. (2016)
  • Author(s): Yamashita T, Ueda M, Saga N, Nanto K, Tasaki M, Masuda T, Misumi Y, Oda S, Fujimoto A, Amano T, Takamatsu K, Yamashita S, Obayashi K, Matsui H, Ando Y.
  • Journal Title: Amyloid Volume: in press Issue: 3 Pages: 207-208
  • DOI: 10.1080/13506129.2016.1202228
  • Peer Reviewed
• [Journal Article] Long-term outcome of patients with hereditary transthyretin V30M amyloidosis with polyneuropathy after liver transplantation. (2016)
  • Author(s): Okumura K, Yamashita T, Masuda T, Misumi Y, Ueda A, Ueda M, Obayashi K, Jono H, Yamashita S, Inomata Y, Ando Y.
  • Journal Title: Amyloid Volume: 23 Issue: 1 Pages: 39-45
  • DOI: 10.3109/13506129.2015.1123149
  • Peer Reviewed
• [Journal Article] Therapeutic effects and prevention of recurrence of acquired idiopathic generalized anhidrosis via intravenous immunoglobulin treatment. (2016)
  • Author(s): Masuda T, Obayashi K, Ueda M, Fujimoto A, Tasaki M, Misumi Y, Ueda A, Nakane S, Yamashita T, Ando Y.
  • Journal Title: J Dermatol Volume: 43 Issue: 3 Pages: 336-337
  • DOI: 10.1111/1346-8138.13182
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Rapid detection of wild-type and mutated transthyretins. (2015)
  • Author(s): Tasaki M, Ueda M, Obayashi K, Motokawa H, Kinoshita Y, Suenaga G, Yanagisawa A, Toyoshima R, Misumi Y, Masuda T, Yamashita T, Ando Y
  • Journal Title: Annals of Clinical Biochemistry Volume: epub Issue: 4 Pages: 508-510
  • DOI: 10.1177/0004563215605541
  • Peer Reviewed
• [Presentation] Quantification of skin denervation in patients with transthyretin amyloid neuropathy. (2018)
  • Author(s): Masuda T, Ueda M, Misumi Y, Matsumoto S, Nomura T, Tasaki M, Yamashita T, Sonoda Y, Obayashi K, Ando Y.
  • Organizer: The XVIth International Symposium on Amyloidosis
  • Int'l Joint Research
• [Presentation] Pupillary autonomic dysfunction as an early biomarker in patients with hereditary transthyretin amyloidosis. (2018)
  • Author(s): Masuda T, Ueda M, Nagatoshi C, Misumi Y, Nomura T, Tasaki M, Yamashita T, Obayashi K, Ando Y.
  • Organizer: The XVIth International Symposium on Amyloidosis
  • Int'l Joint Research
• [Presentation] Two siblings with hereditary transthyretin amyloidosis: a rare TTR variant T49S (p.T69S). (2018)
  • Author(s): Masataka Y, Masuda T, Yamashita T, Ueda M, Misumi Y, Ando T, Masuyama T, Ando Y.
  • Organizer: The XVIth International Symposium on Amyloidosis
  • Int'l Joint Research
• [Presentation] Skin denervation in patients with hereditary and wild-type transthyretin amyloidosis. (2017)
  • Author(s): Masuda T, Ueda M, Misumi Y, Nomura T, Tasaki M, Yamashita T, Obayashi K, Ando Y.
  • Organizer: International Society for Autonomic Neuroscience
  • Int'l Joint Research
• [Presentation] Impact of skin denervation in patients with wild-type transthyretin amyloidosis. (2017)
  • Author(s): Masuda T, Ueda M, Misumi Y, Suenaga G, Matsumoto S, Nomura T, Tasaki M, Yamashita T, Obayashi K, Ando Y.
  • Organizer: XXIII World Congress of Neurology
  • Int'l Joint Research
• [Presentation] Pupillary autonomic nervous dysfunction in hereditary transthyretin amyloidosis. (2017)
  • Author(s): Nagatoshi C, Masuda T, Ueda M, Misumi Y, Nomura T, Tasaki M, Yamashita T, Obayashi K, Ando Y.
  • Organizer: XXIII World Congress of Neurology
  • Int'l Joint Research
• [Presentation] 生検皮膚組織を用いたATTRアミロイドーシスの病態評価. (2017)
  • Author(s): 増田曜章、植田光晴、安東由喜雄
  • Organizer: 第5回日本アミロイドーシス研究会学術集会
  • Invited
• [Presentation] 野生型トランスサイレチンアミロイドーシスにおける小径線維障害の検討. (2017)
  • Author(s): 増田曜章、植田光晴、三隅洋平、野村隼也、松本紗也加、田崎雅義、小阪崇幸、山下太郎、大林光念、安東由喜雄
  • Organizer: 第28回日本末梢神経学会学術集会
• [Presentation] 潰瘍性大腸炎患者の自律神経障害および末梢神経障害の病態解析 (2016)
  • Author(s): 増田曜章, 大林光念, 三隅洋平, 中島昌利, 小林起秋, 徳永竜馬, 吉田直矢, 植田光晴, 樋口理, 中根俊成, 佐々木裕, 馬場秀夫, 安東由喜雄
  • Organizer: 第69回日本自律神経学会
  • Place of Presentation: くまもと県民交流館パレア, 熊本
  • Year and Date: 2016-11-10
• [Presentation] 皮神経に着目して行う小径線維ニューロパチーの早期診断および病態解析. (2016)
  • Author(s): 増田曜章, 大林光念, 安東由喜雄
  • Organizer: 第69回日本自律神経学会
  • Place of Presentation: くまもと県民交流館パレア, 熊本
  • Year and Date: 2016-11-10
• [Presentation] Intraepidermal nerve fiber density as an early diagnostic marker of transthyretin-related familial amyloid polyneuropathy. (2016)
  • Author(s): Masuda T, Ueda M, Suenaga G, Tasaki M, Misumi Y, Yamashita T, Obayashi K, Ando Y
  • Organizer: The XVth International Symposium on Amyloidosis
  • Place of Presentation: Uppsala, Sweden
  • Year and Date: 2016-07-03
  • Int'l Joint Research
• [Presentation] トランスサイレチンアミロイドーシスの表皮内神経線維密度と臨床像の関連 (2016)
  • Author(s): 増田曜章，植田光晴，岡田匡充，田崎雅義，三隅洋平，山下太郎，大林光念，安東由喜雄
  • Organizer: 第57回日本神経学会学術大会
  • Place of Presentation: 神戸コンベンションセンター, 兵庫県
  • Year and Date: 2016-05-18
• [Presentation] MR neurographyを用いたトランスサイレチンアミロイドポリニューロパチーの末梢神経障害の解析. (2016)
  • Author(s): 増田曜章，植田光晴，三隅洋平，田崎雅義，山下太郎，大林光念，北島美香, 安東由喜雄
  • Organizer: 第4回日本アミロイドーシス研究会学術集会
  • Place of Presentation: KKRホテル東京, 東京
• [Presentation] 特発性後天性全身性無汗症に対する免疫グロブリン大量静注療法の効果 (2015)
  • Author(s): 増田曜章、大林光念、三隅洋平、植田明彦、植田光晴、山下太郎、中根俊成、安東由喜雄
  • Organizer: 第68回日本自律神経学会
  • Place of Presentation: ウインクあいち
  • Year and Date: 2015-10-29
• [Presentation] 家族性アミロイドポリニューロパチーの表皮内神経線維密度と臨床像の関連 (2015)
  • Author(s): 増田曜章、植田光晴、田崎雅義、三隅洋平、山下太郎、大林光念、安東由喜雄
  • Organizer: 第3回日本アミロイドーシス研究会学術集会
  • Place of Presentation: KKRホテル東京
  • Year and Date: 2015-08-21
• [Presentation] 家族性アミロイドポリニューロパチーの早期診断における皮膚生検の有用性の検討 (2015)
  • Author(s): 増田曜章、植田光晴、野村隼也、田崎雅義、三隅洋平、山下太郎、大林光念、安東由喜雄
  • Organizer: 第56回日本神経学会学術大会
  • Place of Presentation: 朱鷺メッセ (新潟コンベンションセンター)
  • Year and Date: 2015-05-20
• [Book] 末梢神経障害 (神経内科Clinical Questions & Pearls) (2018)
  • Author(s): 増田曜章, 安東由喜雄
  • Total Pages: 7
  • Publisher: 中外医学社
• [Book] 新時代の臨床糖尿病学 (下): 多角的自律神経機能検査 (小径線維障害) (2016)
  • Author(s): 増田曜章、大林光念、安東由喜雄
  • Total Pages: 4
  • Publisher: 日本臨床
• [Book] 難治性内分泌代謝疾患Update: 全身性アミロイドーシス (2015)
  • Author(s): 増田曜章、安東由喜雄
  • Total Pages: 4
  • Publisher: 診断と治療社
• [Book] 臨床に役立つ神経障害性疼痛の理解: アミロイドーシス (2015)
  • Author(s): 増田曜章、安東由喜雄
  • Total Pages: 6
  • Publisher: 文光堂
• [Remarks] 熊本大学大学院生命科学研究部神経内科学分野
  • URL: http://kumadai-neurology.com/