Modulating the local immune environment via gene transfer to suppress intraocular inflammation

通过基因转移调节局部免疫环境抑制眼内炎症

• 批准号: G1100383/1
• 负责人: Colin Chu
• 金额: $ 29.07万
• 依托单位: University College London
• 依托单位国家: 英国
• 项目类别: Fellowship
• 财政年份: 2011
• 资助国家: 英国
• 起止时间: 2011 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G1100383%2F1
• 关键词: Modulating; local; immune; environment; via

Uveitis is a major cause of blindness in children and the working age population. It is a recurrent autoimmune disease that results in chronic inflammation in several parts of the eye. Autoimmune diseases occur when an individual‘s immune system mistakenly recognizes specific proteins within the body as foreign and mounts an attack against them, producing an inflammatory reaction that can cause irreversible damage. The mainstay of current treatment includes steroids and drugs that dampen the immune response, which may treat the inflammation, but often result in serious side effects. We aim to develop viral gene therapy treatments which alter immune function in the eye and provide long-term, local suppression of inflammation without the need for systemic drugs and their associated side effects. Pre-developed gene carriers called ‘vectors‘ will be tested in a mouse model of uveitis. We will measure the effect on disease severity by examining ocular structure, the level of immune reaction within the eye and by testing visual function. This project will help us understand the predominant inflammatory pathways in uveitis and progress towards a full clinical trial in the near future. The work will additionally inform research into gene therapy for other autoimmune diseases.

葡萄膜炎是导致儿童和劳动年龄人口失明的主要原因。这是一种反复发生的自身免疫性疾病，会导致眼睛几个部位的慢性炎症。当一个人的免疫系统错误地将体内的特定蛋白质识别为外来蛋白质并对它们发动攻击时，就会发生自身免疫性疾病，产生可能造成不可逆转损害的炎症反应。目前的主要治疗方法包括类固醇和抑制免疫反应的药物，这些药物可能治疗炎症，但往往会导致严重的副作用。我们的目标是开发病毒基因疗法，改变眼睛的免疫功能，并在不需要全身药物及其相关副作用的情况下提供长期、局部的炎症抑制。被称为“载体”的预先开发的基因载体将在葡萄膜炎的小鼠模型上进行测试。我们将通过检查眼睛结构、眼睛内的免疫反应水平和视觉功能来衡量对疾病严重程度的影响。该项目将帮助我们了解葡萄膜炎的主要炎症途径，并在不久的将来进行全面的临床试验。这项工作还将为其他自身免疫性疾病的基因治疗研究提供信息。