| Project/Area Number |
13557118
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
Cerebral neurosurgery
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| Research Institution | Tohoku University (2003)
Kyushu University (2001-2002) |
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Principal Investigator |
DOH-URA Katsumi Tohoku University, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (00263012)
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| Co-Investigator(Kenkyū-buntansha) |
IWAKI Toru Tohoku University, Graduate School of Medical Sciences, Professor, 大学院・医学研究院, 教授 (40221098)
村田 充男 大正製薬, 創薬研究所, 主任研究員
松島 俊夫 九州大学, 大学院・医学研究院, 助教授 (40165816)
鈴木 伸之 第一製薬, 創薬第2研究所, 研究員
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| Project Period (FY) |
2001 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥13,300,000 (Direct Cost: ¥13,300,000)
Fiscal Year 2003: ¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 2002: ¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 2001: ¥7,700,000 (Direct Cost: ¥7,700,000)
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| Keywords | prion disease / prophylactic and therapeutic medicine / inhibition of prion biosynthesis / drug screening / persistently infected cell culture / animal experiment / pentsan polysulfate / intracerebroventricular administration / スクリーニング / 脳内感染 / 脳室内持続注入 |
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| Research Abstract |
In Japan, where iatrogenic Creutzfeldt-Jacob disease (CJD) or hereditary prion disease has occurred frequently, development of prophylaxis and therapeutics for prion diseases has been required. This research covered not only the basic research but also the clinical application of the therapeutic development, and the following points were clarified.
1.Many anti-prion compounds were discovered by screening with prion-infected cells. About 20 effective quinoline-ring vhemicals including several clinical medicines were found. More than 80 effective compaunds from benzothiazole-related chemicals or Congo red-related chemicals were discovered, and some of them were effective not only as therapeutic drugs but also as prion imaging probes capable of detecting abnormal prion protein deposition in the brain, when administered peripherally in the disease animal models. Pentosan polysulfate (SPS) and heparin derivatives were also found to he remarkably effective. Especially SPS was the most benefic
… More
ial, when administered intracerebroventricularly into the diseased animals.
On the one hand, interaction analyses between prion protein (PrP) and anti-prion chemicals revealed that most of the anti-prion chemicals exert their anti-prion activities by interacting directly with the PrP and thus inhibiting the abnormal conversion. Correlation between the interaction affinity and the anti-prion activity was demonstrated and thus wan possibly applied to high-throughput screening for anti-prion chemicals. Furthermore, it was shown that anti-prion activities of the anti-prion chemicals were dependent of infected cell types as well as pathogen strains.
2.About SPS which showed the most beneficial effects in the animal models, after checking the safety of its continuous intracerebroventricular infusion in experimental animals, experimental treatment was carried out in one British patient with variant CJD. In spite of his advanced clinical stage, intracerebroventricular SPS administration demonstrated more outstanding effects than expected, and it did not show any adverse effects. The findings in the patient, together with the findings in the animals model experiments, indicate that this treatment can be also used to prevent high-risk people from prion diseases. Less
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