Development of neoglycobiologics and application for drug discovery for lysosomal diseases

2016 Fiscal Year Final Research Report

• Project/Area Number: 26293120
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Applied pharmacology
• Research Institution: The University of Tokushima
• Principal Investigator: ITOH Kohji 徳島大学, 大学院医歯薬学研究部, 教授 (00184656)
• Co-Investigator(Kenkyū-buntansha): 辻 大輔 徳島大学, 大学院医歯薬学研究部, 助教 (00423400) ; 広川 貴次 国立研究開発法人産業技術総合研究所, 創薬分子プロファイリング研究センター, 研究チーム長 (20357867)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: バイオ医薬品 / 糖タンパク製剤 / リソソーム病 / ドラッグデリバリー / 糖鎖工学

Outline of Final Research Achievements

To develop a novel enzyme replacement therapy for Tay-Sachs disease as a lysosomal disease, caused by lysosomal beta-hexosaminidase A (HexA) associated with excessive accumulation of GM2 ganglioside (GM2) and neurological symptoms, a novel recombinant human modified HexB (mod2B) was developed and purified. The intracerebroventricularly administered mod2B had therapeutic effects on restoration of HexA activity, reduction of GM2 accumulated in brain regions, improvement of motor dysfunction and prolongation of life span of HexA-deficient model mice.
We succeeded in producing transgenic silkworm strain overexpressing the human alfa-iduronidase (IDUA) gene in the silk glands, and developed a novel transglycosylation technology to attach the synthetic terminal mannose-6-phosphate (M6P)-carrying N-glycans to the IDUA purified from silk glands and cocoons. The neoglyco-IDUA was taken up by the fibroblasts with IDUA deficiency and reduced the accumulated substrates including heparan sulfates.

Free Research Field

病態生化学、分子治療学