Improvement of peripheral neuropathy by Adeno-associated virus vector expressing a-galactosidase A in murine Fabry model

• Project/Area Number: 15K19637
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pediatrics
• Research Institution: Jikei University School of Medicine
• Principal Investigator: HIGUCHI TAKASHI 東京慈恵会医科大学, 医学部, 助教 (30595327)
• Research Collaborator: OHASHI Toya ; KOBAYASHI Hiroshi ; SHIMADA Yohta
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2017: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: アンダーソン・ファブリー病 / 末梢神経症状 / 痛み / ファブリ病 / 疼痛 / Gb3 / Anderson-Fabry Disease / α-galactosidase A / globotriaosylceramide / TRP channel / dorsal root ganglion / ファブリー病 / 末梢神経障害

Outline of Final Research Achievements

Anderson-Fabry disease (FD) is a lysosomal storage disorder caused by mutation of the alpha-galactosidase A (GLA) gene. Many FD patients have peripheral neuropathy in the childhoods. This is caused by accumulation of globotoriaosylceramide (Gb3) in dorsal root ganglia (DRG). FD murine model expressed Trpv1 mRNA. The express level was same level as wild-type (WT) mice. Unexpectedly, FD mouse did not show pain symptoms in this experiment. FD mouse showed hyposensitivity to the hot-plate test compare to WT mouse. There were many myelin-like granules in the cytosol of FD DRG neuron. However there was not detected in the axon. It was difficult to observe “patient-like” peripheral neuropathy in this murine model. Our data could not clear the relationship between TRPs and peripheral nerve symptoms.

Research Products

• [Presentation] Improvement of peripheral neuropathy in murine Fabry model by intrathecal administration of serotype 9 Adeno-associated virus vector expressing α-galactosidase A (2017)
  • Author(s): TAKASHI HIGUCHI, YOHTA SHIMADA, HIROSHI KOBAYASHI, TAKAHIRO FUKUDA, HIDETOSHI KABURAGI, MITSUHIRO ENOMOTO, FUSAO KATO, HIROYUKI IDA, TOYA OHASHI
  • Organizer: 23rd JSGCT 2017
• [Presentation] Therapeutic strategy for Fabry disease peripheral neuropathy with rAAV vector (2017)
  • Author(s): TAKASHI HIGUCHI, YOHTA SHIMADA, HIROMI HIRAKI, HIROSHI KOBAYASHI, TAKAHIRO FUKUDA, FUSAO KATO, TOYA OHASHI
  • Organizer: 59th JSIMD 2017
• [Presentation] Treatment for Anderson-Fabry disease peripheral neuropathy with adeno-associated virus vector encoded human α- galactosidase A gene in a murine model of Fabry disease (2016)
  • Author(s): T Higuchi, Y Shimada, H Kobayashi, H Ida, T Ohashi
  • Organizer: Society for the Study of Inborn Errors of Metabolism (SSIEM)
  • Place of Presentation: Rome, Italy
  • Year and Date: 2016-09-06
  • Int'l Joint Research
• [Presentation] Treatment for Fabry peripheral neuropathy with Adeno-Associated Virus Vector in Murine Fabry Disease Model (2016)
  • Author(s): T HIGUCHI, Y SHIMADA, H KOBAYASHI, T OHASHI
  • Organizer: Japan Society of Gene and Cell Therapy (JSGCT)
  • Place of Presentation: Tokyo, Japan
  • Year and Date: 2016-07-28