Pathogenesis of HTLV-I-associated inflammation: Exploration through therapeutic intervention

HTLV-I 相关炎症的发病机制：通过治疗干预进行探索

• 批准号: G0401616/1
• 负责人: Graham Taylor
• 金额: $ 50.21万
• 依托单位: Imperial College London
• 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
• 来源: https://gtr.ukri.org/projects?ref=G0401616%2F1
• 关键词: Pathogenesis; HTLV; associated; inflammation; Exploration

HAM/TSP is a chronic disease of the spinal cord, caused by a virus called HTLV-I. Worldwide approximately 20 million persons are infected, many in member states of the Commonwealth. Infection with HTLV-I is lifelong, and about 3% will develop this chronic debilitating disease, of which half will become wheelchair dependent. We, and others, have shown a strong and persistent immune response to HTLV-I in carriers and patients with HAM/TSP, but this fails to clear the virus. However, carriers with a low burden of virus in the blood have a low risk of developing disease. The immune response in these carriers seems better able to kill infected cells. A less efficient response is associated with a higher viral burden that drives the immune response with a resultant release of chemicals by the immune cells that inadvertently cause harm, most especially to cells in the spinal cord. Our understanding of HAM/TSP suggests that targeting the immune response should improve the health of our patients especially if the disease is diagnosed early. To identify the best type of treatment we are planning three studies of drugs that target the immune response in different ways. Each has been used in other inflammatory conditions but never before studied in HAM/TSP. We aim to study the extent and duration of the clinical response and to associatedthis with the different effects that the therapies have on the immune response and on the number of HTLV-I infected cells in the blood. This in turn will improve our knowledge and understanding of the disease and should lead to better therapy. Our results will be shared with our patients through a newsletter and made available on the clinic website.

HAM/TSP是一种由HTLV-I病毒引起的脊髓慢性疾病。全世界约有2 000万人受到感染，其中许多人在英联邦成员国。htlv - 1感染是终生的，约3%的人会发展成这种慢性衰弱性疾病，其中一半人会依赖轮椅。我们和其他人已经在HAM/TSP携带者和患者中显示出对HTLV-I的强烈和持续的免疫反应，但这并不能清除病毒。然而，血液中病毒负荷低的携带者发病风险低。这些携带者的免疫反应似乎更能杀死被感染的细胞。效率较低的反应与较高的病毒负荷有关，病毒负荷驱动免疫反应，导致免疫细胞释放化学物质，无意中造成伤害，尤其是对脊髓细胞。我们对HAM/TSP的理解表明，针对免疫反应可以改善患者的健康状况，特别是如果疾病得到早期诊断。为了找出最好的治疗方法，我们正计划进行三项针对免疫反应的药物研究。每种方法都曾用于其他炎症条件，但从未在HAM/TSP中进行过研究。我们的目标是研究临床反应的程度和持续时间，并将其与治疗对免疫反应和血液中HTLV-I感染细胞数量的不同影响联系起来。这反过来将提高我们对这种疾病的认识和理解，并应该导致更好的治疗。我们的结果将通过通讯与患者分享，并在诊所网站上提供。