Gene therapy for central nervous involvement of Gaucher disease

• Project/Area Number: 11670788
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Pediatrics
• Research Institution: The Jikei University School of Medicine
• Principal Investigator: IDA Hiroyuki Jikei Univ., Dept.of Pediatrics assi prof., 医学部, 講師 (90167255)
• Co-Investigator(Kenkyū-buntansha): HASEGAWA Yoriyasu Jikei Univ., Dept.of Pediatrics senior investigator, 医学部, 助手 (60256435) ; OHASHI Touya Jikei Univ., Dept.of Pediatrics assi prof., 医学部, 講師 (60160595) ; ONO Tsuneya Jikei Univ., Dept.of Pediatrics prof., 医学部, 教授 (60147288) ; ETO Yoshikatsu Jikei Univ., Dept.of Pediatrics prof., 医学部, 教授 (50056909)
• Project Period (FY): 1999 – 2000
• Project Status: Completed (Fiscal Year 2000)
• Budget Amount: ¥3,800,000 (Direct Cost: ¥3,800,000); Fiscal Year 2000: ¥1,400,000 (Direct Cost: ¥1,400,000); Fiscal Year 1999: ¥2,400,000 (Direct Cost: ¥2,400,000)
• Keywords: Gaucher disease / enzyme replacement therapy / phenotype / 遺伝子変異

Research Abstract

Gaucher disease (GD) is one of lipidoses and caused by a deficiency of glucocerebrosidase. This enzyme defect results in accumulation of glucocerebroside in reticuloendothelial systems. Based on the presence and severity of neurological symptoms, GD is classified into three main phenotypes : typel-non-neuronapthic form, type2 -acute neuronopathic form and type 3-subacute neuronopathic form. The clinical hallmark of this disorder is variability in phenotypic expression. This phenotypic variation may result from molecular heterogeneity. Therefore there is no consensus regarding optimal dosage of enzyme.
We investigated the detailed phenotypic expression, genotype-phenotype correlation and optimal treatment in Japanese patients with Gaucher disease.
We reported the rare type 3 form which manifest communicating hydrocephalus and fbrous thickening of spleen and liver capsules. The high incidence of skeletal complications improvement was significant. these observation suggest that macrophages may be good target cells for ex vivo gene therapy Sly disease.

Research Products

• [Publications] Ida H,Rennert OM,Kobayashi M and Eto Y.: "Effects of enzyme replacement therapy in 13 Japanese pediatric patients with Gaucher disease."Eur J Pediatr. (2000)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Shiihara T,Ida H: "Communicating hydrocephalus in a patient with Gaucher's disease type 3."Pediatr Neurol. 22. 234-6 (2000)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Tsuda M,Kitasawa E,Ida H: "A newly recognized missense mutation in the GLUT2 gene in a patient with Fanconi-Bickel syndrome."Eur J Pediatr. 159. 867 (2000)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Ida H, Rennert OM, Kobayashi M and Eto Y.: "Effects of enzyme replacement therapy in 13 Japanese pediatric patients with Gaucher disease."Eur J Pediatr. accepted. (2000)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Shiihara T, Oka A, Suzaki I, Ida H and Takeshita K.: "Communicating hydrocephalus in a patient with Gaucher's disease type 3."Pediatr Neurol. 22. 234-6 (2000)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Tsuda M, Kitasawa E, Ida H, Eto Y and Owada M.: "A newly recognized missense mutation in the GLUT2 gene in a patient with Fanconi-Bickel syndrome."Eur J Pediatr. 159. 867 (2000)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Ida H,Rennert OM,Kobayashi M and Eto Y.: "Effects of enzyme replacement therapy in 13 Japanese pediatric patients with Gaucher disease."Eur J Pediatr. (2000)
• [Publications] Shiihara T,Ida H: "Communicating hydrocephalus in a patient with Gaucher's disease type 3."Pediatr Neurol. 22. 234-6 (2000)
• [Publications] Tsuda M,Ida H: "A newly recognized missense mutation in the GLUT2 gene in a patient with Fanconi-Bickel syndrome."Eur J Pediatr. 159. 867
• [Publications] 井田博幸: "Gaucher病 今日の小児治療指針"医学書院. (2000)
• [Publications] Eto Y., Ida H.: "Clinical and molecular Characteristics of Japanese Gaucher Disease"Neurochem Res. 24(2). 207-211 (1999)
• [Publications] Ida H., Rennert OM., Eto Y., et al.: "Clinical and genetic studies of Japanese homozygotes for the・・・"Hum Genet. 105. 120-126 (1999)
• [Publications] Ida H., Rennert OM., Eto Y., et al.: "Severe skeletal complications in Japanese patients with type1・・・"J Inher Metab Dis. 22. 63-73 (1999)
• [Publications] Oishi K., Kurosawa K., Ida H., et al.: "Clinical and molecular of Japanese patients with neuronal・・・"Molecular Genetics and Metabolism. 66. 344-348 (1999)