最新医学进展:风湿病药物治疗阿尔茨海默病

背景介绍:今日医学新闻主要对生物医学界重要的医学发现或成果进行及时报道。Studies Reveal New Protein Target For Treating Alzheimer's Disease09 Nov 2010Three new studies provide c

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背景介绍:今日医学新闻主要对生物医学界重要的医学发现或成果进行及时报道。
Studies Reveal New Protein Target For Treating Alzheimer's Disease
09 Nov 2010
Three new studies provide converging evidence pointing to a new therapeutic target in Alzheimer's Disease(AD). These studies, from independent academic centers in the U.S., England, and China, point to excess levels of a protein called TNF as a key factor in AD. TNF is an immune signaling protein that regulates both inflammation and neuronal communication in the brain. As a target it is radically different from the amyloid plaques that have been the main focus of AD research for two decades. The new studies suggest the promise of a wholly new way to treat AD.

最新三项分别来自美国,英国,中国的独立研究中心研究提示了AD治疗的新靶标,证明过度分泌的肿瘤坏死因子(TNF)在AD病理机制中起重要作用。肿瘤坏死因子是炎症和脑内神经信号传导的重要调节因子。近20年来TNF作为干预淀粉样斑块的靶标之一被深入研究,新的研究表明干预TNF可以成为全新的AD治疗途径。
The latest study, to be presented at the Annual Meeting of the American College of Rheumatology this week, reports a 55% reduction in risk of developing Alzheimer's dementia for rheumatoid arthritis patients who received anti-TNF treatment compared with controls. The study, entitled "Tumor Necrosis Factor Inhibition Reduces the Incidence of Alzheimer's Disease in Rheumatoid Arthritis Patients" involved a review of the medical and pharmacy claims of 42,193 patients with a pre-existing diagnosis of RA. 165 patients with AD (cases) were matched to 1,393 controls in this nested case-control study. In this population of adults with RA the risk of AD was reduced by TNF inhibitor therapy, but not by other disease modifying agents used for treatment of RA. The authors concluded that TNF may be an important component in the pathogenesis of AD. The study was a collaboration between researchers from Dartmouth Medical School, Massachusetts General Hospital, Verisk Health, and Harvard Medical School.

最新在美国风湿病学年会报告的论文表明,与对照组相比较,接受肿瘤坏死因子(TNF)抗体治疗的风湿病人罹患AD风险降低55%。“下调肿瘤坏死因子(TNF)降低风湿病人罹患AD风险”论文是对42193例风湿病患者进行的巢式病例对照研究得出的结论。与对照组有1393例诊断AD相比,TNF抗体治疗组仅165例,而且充分排除了其它RA药物的可能。该研究来自于美国几所著名医学中心,包括达特茅斯医学院(Dartmouth Medical School), 麻省总医院(Massachusetts General Hospital),Verisk医学评估中心(Verisk Health), 以及哈佛医学院(Harvard Medical School).
The ACR study closely follows on the heels of a study published November 1 in the Proceedings of the National Academy of Sciences entitled "Tumor necrosis factor-alpha triggers a cytokine cascade yielding postoperative cognitive decline". In this collaboration of the Imperial College and Kennedy Institute of Rheumatology in London and UCSF, anti-TNF treatment was found to prevent neuroinflammation and cognitive decline in an animal model of surgery-induced cognitive decline. This study provided further evidence that TNF, widely recognized as playing a key role in arthritis, may also play a key role in cognitive disorders associated with inflammation.
发表在11月1号美国科学院学报(PNAS)的ACR研究,标题为“TNFa导致炎性级联反应造成术后认知功能损害”。来自英国帝国理工大学,伦敦肯尼迪风湿病研究所和美国加州大学旧金山分校多中心研究证实,TNFa抗体可以有效降低麻醉后实验动物认知损害及炎性反应。提示这种长期以来治疗RA的药物有可能对炎性相关的认知障碍有治疗作用。
Just prior to publication of the PNAS study researchers from Nanjing Medical University in China reported that anti-TNF treatment reduced the levels of TNF, amyloid plaques and tau phosphorylation in an animal model, surprisingly as early as three days after beginning treatment. (Brain Research, accepted manuscript published online October 21 entitled "Anti-TNF-alpha reduces amyloid plaques and tau phosphorylation and induces CD11c-positive dendritic-like cell in the APP/PS1 transgenic mouse brains"). The authors of the Brain Research manuscript concluded that their results support the use of anti-TNF for treatment of AD.
而先于这2项研究的来自南京医科大学的研究报道表明,TNFa单克隆抗体可以下调AD转基因小鼠脑内TNFa水平,减轻老年斑及过磷酸化的tau,而且这种神经保护效果在治疗后的3天即可出现。该文章“抗TNFa可以减少APP/PS1转基因小鼠的老年斑及过磷酸化tau,诱导树突样细胞表达”已于10月21日在线发表于脑研究网站。作者认为这项在体研究揭示了AD的抗TNFa治疗新途径。

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