Molecular-targ eted therapy for refractory immune-mediated neuropat hies

• Project/Area Number: 21790839
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Neurology
• Research Institution: Nagoya University
• Principal Investigator: IIJIMA Masahiro Nagoya University, 医学系研究科, COE特任助教 (40437041)
• Project Period (FY): 2009 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2010: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2009: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 免疫性ニューロパチー / 難治性ニューロパチー / rituximab / 新規治療薬 / 多巣性運動ニューロパチー / CIDP / 抗MAG抗体陽性IgM-MGUSニューロパチー / MMN (multifocal motor neuropathy) / IgM MGUSニューロパチー / 新規治療法

Research Abstract

In this study, we demonstrated the effect and safety of rituximab for various refractory immune-mediated neuropathies. Rituximab (375 mg/m^2 intravenously each week for 4 weeks) was administered in an openlabel design to one patient with multifocal motor neuropathy (MMN), one with chronic inflammatory demyelinating polyneuropathy (CIDP), one with neuropathy associated with Sjogren's syndrome (SN), and four with anti-MAG IgM-MGUS neuropathy (IgM-N). Reduction of total IVIg requirements of a patient with MMN, although the effect was only temporary, were suggested to be responded to rituximab. Improvement of clinical status in three patients with IgM-N suggeted that rituximab was well tolerated and is a promising new drug. No adverse events occurred in all patients.

Research Products

• [Journal Article] 末梢神経障害CIDPの遺伝子多型と治療反応性 (2011)
  • Author(s): 飯島正博, 小池春樹, 祖父江元
  • Journal Title: Annual Review神経 Pages: 300-309
• [Journal Article] 末梢神経障害CIDPの遺伝子多型と治療反応性 (2011)
  • Author(s): 飯島正博, 他
  • Journal Title: Annual Review神経2011 Volume: 2011 Pages: 300-309
• [Journal Article] Morphological progression of myelin abnormalities in IgM-monoclonal gammopathy of undetermined significance anti-myelin-associated glycoprotein neuropathy. (2010)
  • Author(s): Kawagashira Y, Koike H, Tomita M, Morozumi S, Iijima M, Nakamura T, Katsuno M, Tanaka F, Sobue G
  • Journal Title: J Neuropathol Exp Neurol. 69 Pages: 1143-1157
  • Peer Reviewed
• [Journal Article] Systemic but asymptomatic transthyretin amyloidosis 8 years after domino liver transplantation. (2010)
  • Author(s): Koike H, Kiuchi T, Iijima M, Ueda M, Ando Y, Morozumi S, Tomita M, Kawagashira Y, Watanabe H, Katsuno M, Shimoyama Y, Okazaki Y, Kamei H, Sobue G
  • Journal Title: J Neurol Neurosurg Psychiatry. (Epub ahead of print)
  • Peer Reviewed
• [Journal Article] Clinicopathological features of acute autonomic and sensory neuropathy. (2010)
  • Author(s): Koike H, Atsuta N, Adachi H, Iijima M, Katsuno M, Yasuda T, Fukada Y, Yasui K, Nakashima K, Horiuchi M, Shiomi K, Fukui K, Takashima S, Morita Y, Kuniyoshi K, Hasegawa Y, Toribe Y, Kajiura M, Takeshita S, Mukai E, Sobue G
  • Journal Title: Brain. 133 Pages: 2881-2896
  • NAID: 10025625514
  • Peer Reviewed
• [Journal Article] IgM MGUS anti-MAG neuropathy with predominant muscle weakness and extensive muscle atrophy. (2010)
  • Author(s): Kawagashira Y, Kondo N, Atsuta N, Iijima M, Koike H, Katsuno M, Tanaka F, Kusunoki S, Sobue G
  • Journal Title: Muscle Nerve. 42 Pages: 433-435
  • Peer Reviewed
• [Journal Article] Differential response to intravenous immunoglobulin (IVIg) therapy among multifocal and polyneuropathy types of painful diabetic neuropathy. (2010)
  • Author(s): Kawagashira Y, Watanabe H, Morozumi S, Iijima M, Koike H, Hattori N, Sobue G
  • Journal Title: J Clin Neurosci. 17 Pages: 1003-1008
  • Peer Reviewed
• [Journal Article] Slowly progressive autonomic neuropathy with antiganglionic acetylcholine receptor antibody. (2010)
  • Author(s): Koike H, Koyano S, Morozumi S, Kawagashira Y, Iijima M, Katsuno M, Hattori N, Vernino S, Sobue G
  • Journal Title: J Neurol Neurosurg Psychiatry. 81 Pages: 586-587
  • Peer Reviewed
• [Journal Article] Pyramidal tract involvement in Guillain-Barre syndrome associated with anti-GM1 antibody. (2010)
  • Author(s): Tomita M, Watanabe H, Morozumi S, Kawagashira Y, Iijima M, Nakamura T, Katsuno M, Koike H, Hattori N, Hirayama M, Kusunoki S, Sobue G
  • Journal Title: J Neurol Neurosurg Psychiatry. 81 Pages: 583-585
  • Peer Reviewed
• [Journal Article] 慢性炎症性脱髄性多発根ニューロパチー(CIDP)の多様性CIDPの臨床像と予後規定因子 (2010)
  • Author(s): 飯島正博, 小池春樹, 祖父江元
  • Journal Title: 神経内科 72 Pages: 275-283
• [Journal Article] Morphological progression of myelin abnormalities in IgM-monoclonal gammopathy of undetermined significance anti-myelin-associated glycoprotein neuropathy (2010)
  • Author(s): Kawagashira Y, et al.
  • Journal Title: J Neuropathol Exp Neurol. Volume: 69 Pages: 1143-1157
  • Peer Reviewed
• [Journal Article] Systemic but asymptomatic transthyretin amyloidosis 8 years after domino liver transplantation (2010)
  • Author(s): Koike H, et al.
  • Journal Title: J Neurol Neurosurg Psychiatry Volume: (Epub ahead of print)
  • Peer Reviewed
• [Journal Article] Clinicopathological features of acute autonomic and sensory neuropathy (2010)
  • Author(s): Koike H, et al.
  • Journal Title: Brain. Volume: 133 Pages: 2881-2896
  • Peer Reviewed
• [Journal Article] IgM MGUS anti-MAG neuropathy with predominant muscle weakness and extensive muscle atrophy (2010)
  • Author(s): Kawagashira Y, et al.
  • Journal Title: Muscle Nerve. Volume: 42 Pages: 433-435
  • Peer Reviewed
• [Journal Article] Differential response to intravenous immunoglobulin (IVIg) therapy Among multifocal and polyneuropathy types of painful diabetic neuropathy (2010)
  • Author(s): Kawagashira, et al.
  • Journal Title: J Clin Neurosci. Volume: 17 Pages: 1003-1008
  • Peer Reviewed
• [Journal Article] Slowly progressive autonomic neuropathy with antiganglionic acetylcholine receptor antibody (2010)
  • Author(s): Koike H, et al.
  • Journal Title: J Neurol Neurosurg Psychiatry Volume: 81 Pages: 586-587
  • Peer Reviewed
• [Journal Article] Pyramidal tract involvement in Guillain-Barrテウ syndrome associated with anti-GM1 antibody (2010)
  • Author(s): Tomita M, et al.
  • Journal Title: J Neurol Neurosurg Psychiatry. Volume: 81 Pages: 583-585
  • Peer Reviewed
• [Journal Article] CIDPの臨床像と予後規定因子 (2010)
  • Author(s): 飯島正博, 他
  • Journal Title: 神経内科 Volume: 72 Pages: 275-283
• [Journal Article] Single nucleotide polymorphism of TAG-1 influences IVIg responsiveness of Japanese patients with CIDP (2009)
  • Author(s): Iijima M, et al.
  • Journal Title: Neurology 73 Pages: 1348-1352
  • Peer Reviewed
• [Journal Article] Distinct characteristics of amyloid deposits in early- and late-onset transthyretin Val3OMet familial amyloid polyneuropathy (2009)
  • Author(s): Koike H, Iijima M, et al.
  • Journal Title: J Neurol Sci. 287 Pages: 178-184
  • Peer Reviewed
• [Journal Article] The significance of carpal tunnel syndrome in transthyretin Val30Met familial amyloid polyneuropathy (2009)
  • Author(s): Koike H, Tijima M, et al.
  • Journal Title: Amyloid (Epub ahead of print)
  • Peer Reviewed
• [Journal Article] Intravenous immunoglobulin treatment for painful sensory neuropathy associated with Sjogren's syndrome (2009)
  • Author(s): Morozumi S, Iijima M, et al.
  • Journal Title: J Neurol Sci. 279 Pages: 57-61
  • NAID: 10025625884
  • Peer Reviewed
• [Presentation] Microscolic polyangiitis剖検例における末梢神経と一般臓器の血管炎の比較 (2010)
  • Author(s): 川頭祐一、飯島正博, ら
  • Organizer: 第22回日本神経免疫学会学術集会
  • Place of Presentation: 東京
  • Year and Date: 2010-03-17
• [Presentation] CIDPの生検末梢神経における遺伝子発現解析 (2010)
  • Author(s): 飯島正博, 他
  • Organizer: 第21回日本末梢神経学会学術集会
  • Place of Presentation: 仙台
• [Presentation] 悪性リンパ腫に関連したニューロパチーの臨床病理学的特徴 (2010)
  • Author(s): 冨田稔, 飯島正博, 他
  • Organizer: 第21回日本末梢神経学会学術集会
  • Place of Presentation: 仙台
• [Presentation] FAP患者からの生体ドミノ肝移植症例の剖検病理所見 (2010)
  • Author(s): 小池春樹、飯島正博, 他
  • Organizer: 第21回日本末梢神経学会学術集会
  • Place of Presentation: 仙台
• [Presentation] 家族歴を認めないFAP ATTR Val30 Metの臨床病理の検討 (2010)
  • Author(s): 小池春樹, 飯島正博, 他
  • Organizer: 第21回日本末梢神経学会学術集会
  • Place of Presentation: 仙台
• [Presentation] シェーグレン症候群に伴うニューロパチーAtaxic formとPainful formの病理学的特 (2010)
  • Author(s): 川頭祐一, 飯島正博, 他
  • Organizer: 第21回日本末梢神経学会学術集会
  • Place of Presentation: 仙台
• [Presentation] Crow-Fukase症候群における臨床的特徴およびミエリン形態異常と脱髄の関係 (2010)
  • Author(s): 橋本里奈, 飯島正博, 他
  • Organizer: 第21回日本末梢神経学会学術集会
  • Place of Presentation: 仙台
• [Presentation] Microscopic polyangiitisにおける末梢神経障害と血管炎の三次元的分布 (2010)
  • Author(s): 両角佐織, 飯島正博, 他
  • Organizer: 第21回日本末梢神経学会学術集会
  • Place of Presentation: 仙台
• [Presentation] Rituximabが著効したIgM M蛋白血症に伴う抗MAG抗体関連ニューロパチーの1例 (2010)
  • Author(s): 藤岡祐介, 飯島正博, 他
  • Organizer: 第28回日本神経治療学会
  • Place of Presentation: 横浜
• [Presentation] 特発性後天性全身無汗症の1例 (2010)
  • Author(s): 原敬史, 飯島正博, 他
  • Organizer: 第28回日本神経治療学会
  • Place of Presentation: 横浜
• [Presentation] CIDPにおける軸索関連分子TAG-1の治療反応性への関与 (2010)
  • Author(s): 飯島正博, 他
  • Organizer: 第51回日本神経学会総会
  • Place of Presentation: 東京
• [Presentation] 悪性リンパ腫に関連したニューロパチーの臨床病理学的特徴 (2010)
  • Author(s): 富田稔、飯島正博, 他
  • Organizer: 第51回日本神経学会総会
  • Place of Presentation: 東京
• [Presentation] 家族歴を認めないFAP ATTR Val30 Metの臨床病理の検討 (2010)
  • Author(s): 小池春樹、飯島正博, 他
  • Organizer: 第51回日本神経学会総会
  • Place of Presentation: 東京
• [Presentation] シェーグレン症候群に伴うニューロパチーAtaxic formとPainful formの病理学的特徴 (2010)
  • Author(s): 川頭祐一、飯島正博, 他
  • Organizer: 第51回日本神経学会総会
  • Place of Presentation: 東京
• [Presentation] Microscolic polyangiitis剖検例における末梢神経と一般臓器の血管炎の比較 (2010)
  • Author(s): 両角佐織、飯島正博, 他
  • Organizer: 第51回日本神経学会総会
  • Place of Presentation: 東京
• [Presentation] EAP患者からの生体ドミノ肝移植症例の剖検病理所見 (2010)
  • Author(s): 小池春樹、飯島正博, 他
  • Organizer: 第21回日本末梢神経学会学術集会
  • Place of Presentation: 仙台
• [Presentation] シェーグレン症候群に伴うニューロパチーAtaxic formとPainful formの病理学的特徴 (2010)
  • Author(s): 川頭祐一, 飯島正博, 他
  • Organizer: 第21回日本末梢神経学会学術集会
  • Place of Presentation: 仙台
• [Presentation] CIDPにおける軸索関連分子TAG-1の治療反応性への関与 (2009)
  • Author(s): 飯島正博, ら
  • Organizer: 第20回日本末梢神経学会学術集会
  • Place of Presentation: 大宮
• [Presentation] 抗MAG抗体陽性IgM-MGUSニューロパチーの脱髄機転と軸索障害 (2009)
  • Author(s): 川頭祐一、飯島正博, ら
  • Organizer: 第20回日本末梢神経学会学術集会
  • Place of Presentation: 大宮
• [Presentation] 急性自律神経性ニューロパチーAuto-immune autonomic ganglionopathyとacute autonomic and sensory neuropathyの比較 (2009)
  • Author(s): 小池春樹、飯島正博, ら
  • Organizer: 第20回日本末梢神経学会学術集会
  • Place of Presentation: 大宮
• [Presentation] 肥厚型chronic inflammatory demylenating polyradiculoneuroapthy 8例における臨床、病理所見、治療反応性の検討 (2009)
  • Author(s): 両角佐織、飯島正博, ら
  • Organizer: 第20回日本末梢神経学会学術集会
  • Place of Presentation: 大宮
• [Presentation] 悪性リンパ腫に関連したニューロパチーの臨床病理学的特徴 (2009)
  • Author(s): 冨田稔、飯島正博, ら
  • Organizer: 第20回日本末梢神経学会学術集会
  • Place of Presentation: 大宮
• [Presentation] 家族性アミロイドポリニューロパチーの若年発症例の高齢発症例比較からみたアミロイド沈着の病態解析 (2009)
  • Author(s): 小池春樹、飯島正博, ら
  • Organizer: 第20回日本末梢神経学会学術集会
  • Place of Presentation: 大宮
• [Presentation] CIDPにおける軸索関連分子TAG-1の治療反応性への関与 (2009)
  • Author(s): 飯島正博, ら
  • Organizer: 第50回日本神経学会総会
  • Place of Presentation: 仙台
• [Presentation] 悪性リンパ腫に関連したニューロパチーの臨床病理学的特徴 (2009)
  • Author(s): 富田稔、飯島正博, ら
  • Organizer: 第50回日本神経学会総会
  • Place of Presentation: 仙台
• [Presentation] 大量メルファラン療法併用自己末梢血幹細胞移植法を試みたPOEMS症候群の1例 (2009)
  • Author(s): 横井風児、飯島正博, ら
  • Organizer: 第50回日本神経学会総会
  • Place of Presentation: 仙台
• [Presentation] 急性自律性感覚性ニューロパチーの臨床病理学的検討 (2009)
  • Author(s): 小池春樹、飯島正博, ら
  • Organizer: 第50回日本神経学会総会
  • Place of Presentation: 仙台
• [Presentation] 抗MAG抗体陽性IgM-MGUSニューロパチーの脱髄機転について (2009)
  • Author(s): 川頭祐一、飯島正博, ら
  • Organizer: 第50回日本神経学会総会
  • Place of Presentation: 仙台
• [Presentation] FAP ATTR Va130Metの若年発症例と高齢発症例の比較からみたアミロイド沈着の病態解析 (2009)
  • Author(s): 高木伸之介、飯島正博, ら
  • Organizer: 第50回日本神経学会総会
  • Place of Presentation: 仙台
• [Presentation] Microscolic polyangiitis剖検例における末梢神経と一般臓器の血管炎の比較 (2009)
  • Author(s): 両角佐織、飯島正博, ら
  • Organizer: 第50回日本神経学会総会
  • Place of Presentation: 仙台
• [Presentation] 多彩な神経所見を呈し、著明な馬尾肥厚を認めた肥厚型CIDP白験例の検討 (2009)
  • Author(s): 辻本昌史、飯島正博, ら
  • Organizer: 第27回日本神経治療学会
  • Place of Presentation: 熊本
• [Book] Clinical Neuroscience (2010)
  • Author(s): 飯島正博
  • Total Pages: 130
  • Publisher: 中外医学社