The importance of Spleen tyrosine kinase (Syk) as a potential therapeutic target in glomerulonephritis

脾酪氨酸激酶 (Syk) 作为肾小球肾炎潜在治疗靶点的重要性

• 批准号: G0901997/1
• 负责人: Stephen McAdoo
• 金额: $ 31.88万
• 依托单位: Imperial College London
• 依托单位国家: 英国
• 项目类别: Fellowship
• 财政年份: 2010
• 资助国家: 英国
• 起止时间: 2010 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G0901997%2F1
• 关键词: importance; Spleen; tyrosine; kinase; Syk

Antibody-mediated diseases are those caused by the body?s immune system targeting our own organs. When this occurs in the kidneys it causes inflammation, called glomerulonephritis. This is a common cause of kidney failure. Current treatments for this condition are not always effective and may have severe side-effects. Better and safer treatment is needed.We have shown that a drug called R788 is extremely effective in treating animals with immune-mediated glomerulonephritis. R788 is also effective in treating humans with other forms of immune-mediated disease, such as rheumatoid arthritis. I would like to investigate whether this drug would be a useful and safe treatment for glomerulonephritis in humans.I will achieve this by comparing the effects of R788 on white blood cells and kidney cells taken from humans and animals with glomerulonephritis. I aim to establish if the drug?s target molecule is present in human cells, and if so, whether it is active in reducing levels of inflammation and the antibodies responsible for autoimmunity. This information may provide the basis for a future clinical trial of R788 in humans with glomerulonephritis.I will undertake this research along with other doctors from the Imperial College Kidney and Transplant Institute in London.

抗体介导的疾病是由身体免疫系统针对我们自身器官引起的疾病。当这种情况发生在肾脏时，会引起炎症，称为肾小球肾炎。这是肾衰竭的常见原因。目前针对这种情况的治疗方法并不总是有效，并且可能会产生严重的副作用。需要更好、更安全的治疗。我们已经证明，一种名为 R788 的药物对于治疗患有免疫介导性肾小球肾炎的动物非常有效。 R788 还可有效治疗人类其他形式的免疫介导疾病，例如类风湿性关节炎。我想研究这种药物是否能有效且安全地治疗人类肾小球肾炎。我将通过比较 R788 对取自患有肾小球肾炎的人类和动物的白细胞和肾细胞的影响来实现这一目标。我的目的是确定该药物的目标分子是否存在于人体细胞中，如果存在，它是否能有效降低炎症水平和负责自身免疫的抗体水平。这些信息可能为未来 R788 在人类肾小球肾炎患者中进行的临床试验提供基础。我将与伦敦帝国理工学院肾脏和移植研究所的其他医生一起进行这项研究。