| Project/Area Number |
13670841
|
|---|
| 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 H (2002) Jikei Univ, Dept. of Pediatrics asso prof, 医学部, 助教授 (90167255)
洲鎌 盛一 (2001) 東京慈恵会医科大学, 医学部, 助手 (10154452)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
SUGAMA S Jikei Univ, Dept. of Pediatrics assi prof, 医学部, 講師 (10154452)
OHASHI T Jikei Univ, Dept. of Pediatrics asso prof, 医学部, 助教授 (60160595)
長谷川 頼康 東京慈恵会医科大学, 医学部, 助手 (60256435)
井田 博幸 東京慈恵会医科大学, 医学部, 講師 (90167255)
|
|---|
| Project Period (FY) |
2001 – 2002
|
| Project Status |
Completed (Fiscal Year 2002)
|
| Budget Amount *help |
¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 2002: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2001: ¥1,600,000 (Direct Cost: ¥1,600,000)
|
|---|
| Keywords | lipidosis / gene therapy / mouse model / CNS involvement / 神経細胞 / Krabbe病 / Twitcherマウス / アデノウイルスベクター / 胎児治療 |
|---|
| Research Abstract |
We investigated the effectiveness of gene therapy to lipidosis mouse model. Krabbe disease is caused by a deficiency of galactocerebiostdase (GALC). This enzyme defect resuts in accumulation of psychosine which leads severe demyelination and the occurrence of globoid cells.Twitcher mouse is a murine model of human Krabbe disease. This model mouse manifests twitching and body weight loss, and ultimately dies at 5 weeks after birth. We injected recombinant adenovirus encoding GALC into the lateral ventricle of twitcher mice at birth. Significant improvements in motor functions, body weight and twitching and a prolonged life span were observed. GALC activity was increased to 15% that of normal littermates and psychosine concentration was decreased to 55% that of untreated twitcher mice at postnatal day 15 (PND 15). The number of globoid cells in brain stem was also reduced significantly at PND 35. In contrast, when adenoviruses were injected to the twitcher mice at PND 15, almost no improvements were observed. These data demonstrate that the timing of gene transfer may be of great importance in Krabbe disease.
|
