Therapeutic trial of prion infected mice by continuous infusion of anti-prion agent to brain

通过向脑部持续输注抗朊病毒剂对感染朊病毒的小鼠进行治疗试验

• 批准号: 13670653
• 负责人: SHIRABE Susumu
• 金额: $ 2.18万
• 依托单位: Graduate School of Biomedical Sciences, Nagasaki University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13670653/
• 关键词: Prion; Creutz feldt・Jakob disease; Autiseuse; Monpliosimno; Treatment; モルフォリノ

1) We established prion-infected cell line to evaluate in-vitro effect of anti-prion agents.2) We screened chemical agents and already existing medicines which may have possible anti-prion effect.3) Pentosan Polysulfate (PPS) showed maximum anti-prion effect among the agents we tested.4) To acquirer increased ratio of brain delivery, we are try to modifying PPS by chemical reactions.5) Morphorino failed to reduce PrPc production in vitro.6) We established the clinical protocol of patients with Prion disease using PPS and Quinacrine.

1)我们建立了朊病毒感染的细胞系，以评价抗朊病毒药物的体外作用; 2）筛选了可能具有抗朊病毒作用的化学药物和现有药物; 3）在我们测试的药物中，戊聚糖多硫酸酯（PPS）显示出最大的抗朊病毒作用; 4）为了获得增加脑递送率，5）Morphorino在体外不能抑制PrPc的产生。6）我们建立了用PPS和奎纳克林治疗朊病毒病的临床方案。

项目成果

R Atarashi, S Sakaguchi, K Shigematsu, K Arima, N Okimura, N Yamaguchi, A Li, J Kopacek and S Katamine: "Abnormal activation of glial cells in the brains of prion protein-deficient mice ectopically expressing prion protein-like protein, PrPLP/Dpl"Molecula

R Atarashi、S Sakaguchi、K Shigematsu、K Arima、N Okimura、N Yamaguchi、A Li、J Kopacek 和 S Katamine：“朊病毒蛋白缺陷小鼠大脑中神经胶质细胞异常激活，异位表达朊病毒蛋白样蛋白，

S Nakane, et al.: "Compararative molecular analysis of proviral DNA in HTLV-I-associated myelopathy in monozygotic twins."J Neuro Virol. 6. 275-283 (2000)

S Nakane 等人：“同卵双胞胎 HTLV-I 相关脊髓病中前病毒 DNA 的比较分子分析。”J Neuro Virol。

Kambara C, et al.: "Increased sialyl Lewis^x antigen-positive cells mediated by HTL V-I infection in peripheral blood CD4+T lymphocytes in patients with HTL V-I-associated myelopathy"J Neuroimmunol. 125. 179-184 (2002)

Kambara C 等人：“HTL V-I 相关脊髓病患者外周血 CD4 T 淋巴细胞中 HTL V-I 感染介导的唾液酸化 Lewis^x 抗原阳性细胞增加”J Neuroimmunol。

調 漸: "今日の治療指針"医学書院. 2 (2003)

Susumu Cho：《当今的治疗指南》Igaku Shoin 2 (2003)。

T Fujimoto, T Nakamura, Y Nishiura, K Ichinose, T Furuya, S Shirabe, K Eguchi: "Up-regulation of interleukin-12 receptor expression in peripheral blood mononuclear cells of patients with HTLV-I-associated myelopathy/tropical spastic paraparesis"Journal of

T Fujimoto、T Nakamura、Y Nishiura、K Ichinose、T Furuya、S Shirabe、K Eguchi：“HTLV-I 相关脊髓病/热带痉挛性截瘫患者外周血单核细胞中白细胞介素 12 受体表达的上调”