Translating experimental stroke therapy to patients: determination of optimal dosing and biological efficacy of IL-1ra

将实验性中风疗法应用于患者:确定 IL-1ra 的最佳剂量和生物学功效

基本信息

  • 批准号:
    G0502030/1
  • 负责人:
  • 金额:
    $ 66.31万
  • 依托单位:
  • 依托单位国家:
    英国
  • 项目类别:
    Research Grant
  • 财政年份:
    2006
  • 资助国家:
    英国
  • 起止时间:
    2006 至 无数据
  • 项目状态:
    已结题

项目摘要

Stroke is the third biggest killer world wide and the most common cause of adult disability in the UK. Deaths caused by stroke will nearly double in the next decade. Despite this, there are few treatments.Many studies of potential new treatments have failed, some because it was not fully understood how the treatment worked and how best to give it.A stroke occurs when the blood supply to the brain is disrupted. This causes inflammation in the brain. We have been working on a possible new treatment for stroke, called IL-1ra. IL-1ra is a copy of a naturally occurring chemical that blocks inflammation and is already used in diseases like rheumatoid arthritis. It would be given soon after a stroke and would work by protecting brain cells from damage. We have given IL-1ra to a small number of stroke patients to check that is safe. We are planning to move on to the next stage of developing the treatment (Phase III study) to see how effective it is. Before we do this we want to be sure we are giving the right dose, in the best way.We have completed a study which looked at how the IL-1ra gets into brain from the blood stream. This study was done in patients with subarachnoid haemorrhage (SAH) who had a tube draining fluid (cerebrospinal fluid, CSF) from around the brain to relieve pressure. We collected samples of the CSF to measure IL-1ra and found that it can take up to four hours to reach protective levels. After a stroke we need to get enough IL-1ra into the brain as quickly as possible to protect it from damage. In the proposed studies we want to:1. Give different amounts of IL-1ra to find the dose that gets enough IL-1ra into the CSF quickly. 2. Measure the effect of IL-1ra on inflammation in the brain of patients with SAH, using the dose found in study 1. This will be done by measuring markers of inflammation in samples of CSF and from within the brain (using a technique called microdialysis).3. Give IL-1ra to patients with stroke to check whether it is having the same effect as in patients with SAH. This will ensure that we design the safest and most effective clinical trial that we can.
中风是世界上第三大杀手,也是英国成人残疾的最常见原因。中风造成的死亡人数在未来十年将增加近一倍。尽管如此,治疗方法仍然很少。许多潜在的新治疗方法的研究都失败了,其中一些是因为没有完全理解治疗的原理以及如何最好地给予治疗。当大脑的血液供应中断时,就会发生中风。这会导致大脑发炎。我们一直在研究一种可能的中风新疗法,称为IL-1 ra。IL-1 ra是一种天然存在的化学物质的复制品,可以阻止炎症,并且已经用于类风湿性关节炎等疾病。它将在中风后不久给予,并通过保护脑细胞免受损伤而发挥作用。我们已经给了一小部分中风患者IL-1 ra,以检查其安全性。我们计划进入下一阶段的治疗(III期研究),看看它的有效性。在此之前,我们要确保我们以最好的方式给予正确的剂量,我们已经完成了一项研究,研究了IL-1 ra如何从血液进入大脑。这项研究是在蛛网膜下腔出血(SAH)患者中进行的,这些患者从大脑周围引流液体(脑脊液,CSF)以缓解压力。我们收集了CSF样本来测量IL-1 ra,发现它可能需要长达四个小时才能达到保护水平。中风后,我们需要尽快让足够的IL-1 ra进入大脑,以保护它免受损害。在拟议的研究中,我们希望:1。给予不同量的IL-1 ra,以找到使足够的IL-1 ra迅速进入CSF的剂量。2.使用研究1中发现的剂量测量IL-1 ra对SAH患者大脑炎症的影响。这将通过测量CSF样品和大脑内的炎症标志物(使用称为微透析的技术)来完成。3.给予中风患者IL-1 ra,以检查其是否与SAH患者具有相同的效果。这将确保我们设计出最安全、最有效的临床试验。

项目成果

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Nancy Rothwell其他文献

100 NF-κB Activation by Mal/Tirap is Regulated by Caspase-1
  • DOI:
    10.1016/j.cyto.2007.07.105
  • 发表时间:
    2007-07-01
  • 期刊:
  • 影响因子:
  • 作者:
    Sinead M. Miggin;Eva Pålsson-McDermott;Aisling Dunne;Caroline Jefferies;Emmanuel Pinteaux;Kathy Banahan;Caroline Murphy;Paul Moynagh;Masahiro Yamamoto;Shizuo Akira;Nancy Rothwell;Douglas Golenbock;Katherine A. Fitzgerald;Luke A.J. O’Neill
  • 通讯作者:
    Luke A.J. O’Neill

Nancy Rothwell的其他文献

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{{ truncateString('Nancy Rothwell', 18)}}的其他基金

Impact of peripheral inflammation on cerebrovascular disease
周围炎症对脑血管疾病的影响
  • 批准号:
    G0802001/1
  • 财政年份:
    2009
  • 资助金额:
    $ 66.31万
  • 项目类别:
    Research Grant
Mechanisms of interleukin-1 action in neuronal injury
IL-1在神经元损伤中的作用机制
  • 批准号:
    G0801296/1
  • 财政年份:
    2009
  • 资助金额:
    $ 66.31万
  • 项目类别:
    Research Grant
Combinatorial Systems Biology of ROS-Regulated Interleukin-1 Gene Expression
ROS 调节的 IL-1 基因表达的组合系统生物学
  • 批准号:
    BB/F018398/1
  • 财政年份:
    2008
  • 资助金额:
    $ 66.31万
  • 项目类别:
    Research Grant
Mechanisms of interleukin-1 action in neuronal injury
IL-1在神经元损伤中的作用机制
  • 批准号:
    G19/41/1
  • 财政年份:
    2008
  • 资助金额:
    $ 66.31万
  • 项目类别:
    Fellowship

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