| Project/Area Number |
17590882
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Neurology
|
|---|
| Research Institution | Nagasaki University |
|---|
Principal Investigator |
SHIRABE Susumu Nagasaki University, Hospital of Medicine and Dentistry, Professor, 医学部・歯学部附属病院, 教授 (40264220)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
KATAMINE Shigeru Nagasaki University, Graduate School of Biomedical Sciences, Professor, 大学院医歯薬学総合研究科, 教授 (40161062)
FURUKAWA Hisako Nagasaki University, Graduate School of Biomedical Science, Visiting researcher, 大学院医歯薬学総合研究科, 客員研究員 (80341452)
NISHIDA Noriyuki Nagasaki University, Graduate School of Biomedical Science, Assistant professor, 大学院医歯薬学総合研究科, 助教授 (40333520)
|
|---|
| Project Period (FY) |
2005 – 2006
|
| Project Status |
Completed (Fiscal Year 2006)
|
| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2005: ¥1,800,000 (Direct Cost: ¥1,800,000)
|
|---|
| Keywords | prion / PPS / low-molecular weight PPS / BBB / クロイツフェルト・ヤコブ病 / 治療法開発 / 低分子化 |
|---|
| Research Abstract |
The aim of this study was a trial of of development of therapeutic using PPS modified penetrating efficacy into brain. So far, Pentosan polysalfate (PPS) has been recognized as most effective agent among known anti-prion agent. Therefor, we designed to fractionate PPS to get low-molecular weight PPS (LMW-PPS). The concept to purify LMW-PPS is to raise the efficacy of penetration of Blood Brain Barrier (BBB).
We applied three methods to fractionate PPS. 1) acid hydrolyzation methods 2) gel filtration 3) limiting dilution by LMW-PPS we obtained was aprox. 50-60% of original compound in molecular weight in agerrage. (molecular weight of PPS:4,700 Kd) Using these methods, aproximately same size were obtained. These LMW-PPS fractions were aplied to cell line, which produce abnormal prion proten to see the anti-prion effects. Most effecteive fraction was used for anaima experiments to evaluate in vivo efficacy.
RESULTS
1) LMW-PPS were obtained by three different methods.
2) These LMW-PPS fractions showed anti-prion effect at the concentration of 1μg/ml in prion-infected cell lines.
3) By in vivo sutudy, only mice which were inoculated LMW-PPS intraventrilularly survived significantly longer than control. No significance was observed among the mice, which were injected intraperitonealy. This result indicated that the LMW-PPS could not be a candate for therapeutic agent.
|
