Effect of co-administration with analogs on enzyme preparation

• Project/Area Number: 25860399
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Applied pharmacology
• Research Institution: Meiji Pharmaceutical University
• Principal Investigator: TSUKIMURA TAKAHIRO 明治薬科大学, 薬学部, 助教 (50632783)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 酵素製剤 / 基質類似体 / リソソーム病 / ファブリー病

Outline of Final Research Achievements

We found a compound which stabilize modified α-N-acetylgalactosaminidase (NAGA). The compound enhanced the uptake of modified NAGA into cultured fibroblasts derived from Fabry patients. But the compound did not enhance the uptake of modified NAGA into organs of Fabry mice. We also constructed a new screening method using thermal shift assay.

Research Products

• [Journal Article] Distributions of globotriaosylceramide isoforms, and globotriaosylsphingosine and its analogues in an α-galactosidase A knockout mouse, a model of Fabry disease (2015)
  • Author(s): Sueoka H, Aoki M, Tsukimura T, Togawa T, Sakuraba H
  • Journal Title: PLOS ONE Volume: 10 Issue: 12 Pages: e0144958-e0144958
  • DOI: 10.1371/journal.pone.0144958
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Clinical and biochemical investigation of male patients exhibiting membranous cytoplasmic bodies in biopsied kidney tissues － A pitfall in diagnosis of Fabry disease (2015)
  • Author(s): Sakuraba H., Tsukimura T., Tanaka T., Togawa T., Takahashi N., Mikami D., Wakai S., Akai Y.
  • Journal Title: J. Nephropathol. Volume: 4 Pages: 91-96
  • Peer Reviewed / Open Access
• [Journal Article] Rapid immunochromatographic detection of serum α-galactosidase A antibodies in Fabry patients after enzyme replacement therapy (2015)
  • Author(s): Nakano S, Tsukimura T, Togawa T, Ohashi T, Kobayashi M, et al.
  • Journal Title: PLOS ONE Volume: 10 Issue: 6 Pages: e0128351-e0128351
  • DOI: 10.1371/journal.pone.0128351
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Nano-LC-MS/MS for quantification of Lyso-Gb3 and its analogues reveals a useful biomarker for Fabry disease (2015)
  • Author(s): Sueoka H, Ichihara J, Tsukimura T, Togawa T, Sakuraba H
  • Journal Title: PLOS ONE Volume: 10 Issue: 5 Pages: e0127048-e0127048
  • DOI: 10.1371/journal.pone.0127048
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] A heterozygous female with Fabry disease due to a novel α-galactosidase A mutation exhibits a unique synaptopodin distribution in vacuolated podocytes. (2015)
  • Author(s): Takahashi N, Yokoi S, Kasuno K, Kogami A, Tsukimura T, Togawa T, Saito S, Ohno K, Hara M, Kurosawa H, Hirayama Y, Kurose T, Yokoyama Y, Mikami D, Kimura H, Naiki H, Sakuraba H, Iwano M.
  • Journal Title: Clin Nephrol. Volume: 83 Issue: 05 Pages: 301-308
  • DOI: 10.5414/cn108317
  • Peer Reviewed / Open Access
• [Journal Article] Thirty-seven amino acids and three related nitrogen compounds in human seminal plasma: multivariate analyses reveal strong correlations among asparagine, glutamine, and ammonia with sperm parameters (2015)
  • Author(s): Katayama M., Kaneko S., Tsukimura T., Takamatsu K., Togawa T.
  • Journal Title: Indian J. App. Res. Volume: 5 Pages: 199-203
  • Peer Reviewed
• [Journal Article] Plasma mutant α-galactosidase A protein and globotriaosylsphingosine level in Fabry disease (2014)
  • Author(s): Tsukimura T., Nakano S., Togawa T., Tanaka T., Saito S., Ohno K., Shibasaki F., Sakuraba H.
  • Journal Title: Molecular Genetics and Metabolism Reports Volume: １ Pages: 288-298
  • DOI: 10.1016/j.ymgmr.2014.07.005
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Comparative study on mannose 6-phosphate residue contents of recombinant lysosomal enzymes. (2014)
  • Author(s): Togawa T., Takada M., Aizawa Y., Tsukimura T., Chiba Y., Sakuraba H.
  • Journal Title: Mol. Genet. Metab. Volume: 111 Issue: 3 Pages: 369-373
  • DOI: 10.1016/j.ymgme.2013.12.296
  • Peer Reviewed
• [Journal Article] Molecular basis of 1-deoxygalactonojirimycin arylthiourea binding to human -galactosidase: Pharmacological chaperoning efficacy on Fabry disease mutants. (2014)
  • Author(s): Yu Y,
  • Journal Title: ACS Chem Biol Volume: 9 Issue: 7 Pages: 1460-1469
  • DOI: 10.1021/cb500143h
  • Peer Reviewed
• [Journal Article] A case of Fabry nephropathy with histological features of oligonephropathy. (2014)
  • Author(s): Nishida M, Kosaka K, Hasegawa K, Nishikawa K, Itoi T, Tsukimura T, Togawa T, Sakuraba H, Hamaoka K.
  • Journal Title: Eur J Pediatr Volume: 173 Issue: 8 Pages: 1111-1114
  • DOI: 10.1007/s00431-013-2118-0
  • Peer Reviewed
• [Journal Article] Development of a highly sensitive immuno-PCR assay for the measurement of alpha-galactosidase A protein levels in serum and plasma (2013)
  • Author(s): Nakano, S. Morizane, Y. Makisaka, N. Suzuki, T. Togawa, T. Tsukimura, T. Kawashima, I. Sakuraba, H. Shibasaki, F.
  • Journal Title: PLoS One Volume: 8 Issue: 11 Pages: e78588-e78588
  • DOI: 10.1371/journal.pone.0078588
  • Peer Reviewed
• [Journal Article] Human α-L-iduronidase uses its own N-glycan as a substrate-binding and catalytic module (2013)
  • Author(s): Maita N, Tsukimura T, Taniguchi T, Saito S, Ohno K, Taniguchi H, Sakuraba H
  • Journal Title: Proc. Natl. Acad. Sci. USA. Volume: 110 Issue: 36 Pages: 14628-14633
  • DOI: 10.1073/pnas.1306939110
  • Peer Reviewed
• [Journal Article] Screening for Fabry disease in patients with left ventricular hypertrophy. (2013)
  • Author(s): Mawatari K, Yasukawa H, Oba T, Nagata T, Togawa T, Tsukimura T, Kyogoku S, Ohshima H, Minami T, Sugi Y, Sakuraba H, Imaizumi T.
  • Journal Title: Int J Cardiol Volume: 167 Issue: 3 Pages: 1059-1061
  • DOI: 10.1016/j.ijcard.2012.10.076
  • Peer Reviewed
• [Presentation] Anti-α-galactosidase A antibodies and serum-mediated inhibition in Fabry disease (2016)
  • Author(s): Tsukimura T., Shibasaki F., Shigenaga M., Togawa T., Sakuraba H.
  • Organizer: 12th Annual Lysosomal disease network WORLD Symposium 2016
  • Place of Presentation: Manchester Grand Hyatt San Diego（USA, San Diego）
  • Year and Date: 2016-02-29
  • Int'l Joint Research
• [Presentation] Comparative study on α-galactosidase A (GLA) genetic variants with unknown clinical significance (2016)
  • Author(s): Sakuraba H., Togawa T., Tsukimura T., Saito S., Ohno K
  • Organizer: 12th Annual Lysosomal disease network WORLD Symposium 2016
  • Place of Presentation: Manchester Grand Hyatt San Diego（USA, San Diego）
  • Year and Date: 2016-02-29
  • Int'l Joint Research
• [Presentation] Measurement of glycosphingolipids by means of tandem mass spectrometry and evaluation of them as a biomarker of Fabry disease (2016)
  • Author(s): Togawa T., Kodama T., Tsukimura T., Kawashima I., Tanaka T., Shiga T., Sato A., Sakuraba H.
  • Organizer: 12th Annual Lysosomal disease network WORLD Symposium 2016
  • Place of Presentation: Manchester Grand Hyatt San Diego（USA, San Diego）
  • Year and Date: 2016-02-29
  • Int'l Joint Research
• [Presentation] 酵素製剤に対する抗体を産生したファブリー病患者の血清は酵素製剤の活性を阻害する (2015)
  • Author(s): 重永 雅志、月村 考宏、佐藤 温子、芝崎 太、兎川 忠靖、櫻庭 均
  • Organizer: 第38回日本分子生物学会年会／第88回日本生化学会大会 合同大会
  • Place of Presentation: 神戸ポートアイランド（兵庫県神戸市）
  • Year and Date: 2015-12-01
• [Presentation] 遅発型ファブリー病の原因変異vs機能的多型 (2015)
  • Author(s): 月村 考宏、田中 利絵、大塚 智子、志賀 智子、末岡 英明、芝崎 太、兎川 忠靖、櫻庭 均
  • Organizer: 第57回日本先天代謝異常学会／第13回アジア先天代謝異常症シンポジウム
  • Place of Presentation: 大阪国際会議場（大阪府大阪市）
  • Year and Date: 2015-11-12
• [Presentation] Fabry病モデルマウス腎臓に蓄積する糖脂質の特徴と酵素補充療法による分解効果 (2015)
  • Author(s): 兎川 忠靖、児玉 敬、月村 考宏、川島 育夫、志賀 智子、田中 利絵、櫻庭 均
  • Organizer: 第57回日本先天代謝異常学会／第13回アジア先天代謝異常症シンポジウム
  • Place of Presentation: 大阪国際会議場（大阪府大阪市）
  • Year and Date: 2015-11-12
• [Presentation] 酵素補充療法を受けたファブリー病患者における抗α-ガラクトシダーゼA抗体産生と酵素活性阻害作用 (2015)
  • Author(s): 重永 雅志、月村 考宏、佐藤 温子、芝崎 太、兎川 忠靖、櫻庭 均
  • Organizer: 第57回日本先天代謝異常学会／第13回アジア先天代謝異常症シンポジウム
  • Place of Presentation: 大阪国際会議場（大阪府大阪市）
  • Year and Date: 2015-11-12
• [Presentation] タンデムマス測定法による血漿lyso-Gb3の高感度測定とそのファブリー病バイオマーカーとしての評価 (2015)
  • Author(s): 兎川 忠靖、田中 利絵、志賀 智子、大塚 智子、佐藤 温子、児玉 敬、月村 考宏、櫻庭 均
  • Organizer: 第20回日本ライソゾーム病研究会
  • Place of Presentation: 東京慈恵医科大学（東京都港区）
  • Year and Date: 2015-10-02
• [Presentation] 男性不妊患者精漿中の金属およびアミノ酸の解析: 加齢の影響 (2015)
  • Author(s): 片山昌勅、月村考宏、高松潔、兼子智、兎川忠靖
  • Organizer: 第59回日本薬学会 関東支部大会
  • Place of Presentation: 日本大学（千葉県船橋市）
  • Year and Date: 2015-09-12
• [Presentation] High risk screening for Fabry disease in Japan (2015)
  • Author(s): Tsukimura T., Togawa T., Sakuraba H.
  • Organizer: The 3rd Asian Congress for Lysosomal Storage Disease Screening
  • Place of Presentation: 品川プリンスホテル（東京都港区）
  • Year and Date: 2015-06-19
  • Int'l Joint Research / Invited
• [Presentation] Fabry病患者由来iPS細胞を用いた新規疾患モデルの作製 (2015)
  • Author(s): 那須 誠、天久 朝廷、横路 三有紀、月村 考宏、沖田 圭介、赤井 靖宏、櫻庭 均、 深水 圭、奥田 誠也、長船 健
  • Organizer: 第58回日本腎臓学会学術総会
  • Place of Presentation: 名古屋国際会議場（愛知県名古屋市）
  • Year and Date: 2015-06-05
• [Presentation] 新規改変酵素の免疫交差性及びiPS細胞由来心筋細胞への取り込み‐ファブリー病治療への応用 (2015)
  • Author(s): 月村 考宏、小川 泰弘、大石 一彦、重永 雅志、鶴巻 舞子、兎川 忠靖、櫻庭 均
  • Organizer: 薬学会第135年会
  • Place of Presentation: 神戸
  • Year and Date: 2015-03-25 – 2015-03-28
• [Presentation] Comprehensive study of Fabry disease: Gene mutation, GLA activity, GLA protein and globotriaosylsphingosine (2015)
  • Author(s): Tsukimura T., Togawa T., Sakuraba H.
  • Organizer: 11th Annual Lysosomal disease network WORLD Symposium 2015
  • Place of Presentation: Orlando
  • Year and Date: 2015-02-10 – 2015-02-12
• [Presentation] ファブリー病患者の遺伝子変異、血漿中GLA蛋白質濃度及びLyso-Gb3濃度の関係 (2014)
  • Author(s): 月村 考宏、中野 早知栄、兎川 忠靖、田中 利絵、片山 昌勅、齋藤 静司、芝崎 太、櫻庭 均
  • Organizer: 第56回日本先天代謝異常学会総会/第12回アジア先天代謝異常症シンポジウム
  • Place of Presentation: 仙台
  • Year and Date: 2014-11-13 – 2014-11-15
• [Presentation] ファブリー病患者の血漿中のα-ガラクトシダーゼA蛋白質濃度とグロボトリアオシルスヒィンゴシン濃度の相関性 (2014)
  • Author(s): 月村 考宏、中野 早知栄、兎川 忠靖、田中 利絵、片山 昌勅、齋藤 静司、芝崎 太、櫻庭 均
  • Organizer: 第87回日本生化学会大会
  • Place of Presentation: 京都
  • Year and Date: 2014-10-15 – 2014-10-18
• [Presentation] ファブリー病の分子病態研究：遺伝子変異、変異酵素蛋白質及び蓄積糖脂質について (2014)
  • Author(s): 月村考宏、中野早知栄、兎川忠靖、田中利絵、片山昌勅、齋藤静司、芝崎太、櫻庭均
  • Organizer: 薬学会第134年会
  • Place of Presentation: 熊本
• [Presentation] Molecular interaction between a mutant α-galactosidase A and imino sugars (2014)
  • Author(s): Tsukimura T, Togawa T, Sakuraba H.
  • Organizer: １0th Annual Lysosomal disease network WORLD Symposium 2014
  • Place of Presentation: San Diego
• [Presentation] Comparative study on the content of mannose 6-phosphate residues of recombinant lysosomal enzymes. (2013)
  • Author(s): Tsukimura T, Takada M, Aizawa Y, Suzuki T, Katayama M, Sakuraba S, Togawa T.
  • Organizer: The 55th Annula Meeting of The Japanese Society for Inherited Metabolic Disease/The 3rd Asia Congress for Inherited Metabolic Disease
  • Place of Presentation: 千葉
• [Presentation] マンノース‐6‐リン酸残基の新規定量法の開発：組換えヒトリソソーム酵素解析への応用 (2013)
  • Author(s): 月村考宏、高田大、相澤良明、鈴木俊宏、片山昌勅、櫻庭均、兎川忠靖
  • Organizer: 第86回日本生化学会大会
  • Place of Presentation: 横浜