Developing new tests and treatments to enable prevention of osteoarthritis.

开发新的测试和治疗方法以预防骨关节炎。

• 批准号: MR/Y003470/1
• 负责人: Fiona Watt
• 金额: $ 75.33万
• 依托单位: Imperial College London
• 依托单位国家: 英国
• 项目类别: Fellowship
• 财政年份: 2024
• 资助国家: 英国
• 起止时间: 2024 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FY003470%2F1
• 关键词: Developing; new; tests; treatments; enable

Osteoarthritis (OA) is the commonest form of arthritis, affecting 8.5 million people in the UK. It has an associated healthcare budget estimated at £2 billion, with much greater societal cost. Other than expensive joint replacement, we currently have no drug treatments that prevent, slow or cure OA. Knee joint injuries are the biggest risk factor for future knee OA. About half of all people with knee injuries such as ligament tears will develop OA; surgery to treat the injury does not reduce this risk. This type of OA is known as 'post-traumatic osteoarthritis' (PTOA). Individuals with PTOA are often younger, but we don't know if this form is otherwise the same as 'usual' (idiopathic) OA. Studying people with joint injury and with PTOA gives an unrivalled opportunity to understand the processes which cause OA, and to aim to prevent OA by measuring and targeting these processes.So far we have shown that there is an inflammation response in the knee to injury which varies considerably between people. This initial 'joint injury response' is linked to later symptoms associated OA. Initial findings are that two representative 'markers' in knee joint fluid (synovial fluid), increased blood and increased fluid in the joint at the time of injury all act as markers of worse outcome in those with knee injury. In UK Biobank work, we showed that being older at the time of injury and being female also increase risk of OA after knee injury. Known 'OA genes' did not particularly add to this risk (though we cannot be sure until we finish studies in bigger numbers). We also found a possible new gene association (not previously seen with OA) which will need to be tested further.My overall goal is to develop new knowledge that will benefit patients and the NHS, with the main aim of being able to run clinical trials of new treatments that seek to prevent OA. These trials importantly focus on people who have experienced knee joint injury or in other high risk groups for developing knee OA.There are three main aims and related objectives:1. I will aim to show how similar or different PTOA and idiopathic OA are, by looking at many (thousands) of proteins in the joint fluid of individuals in these two groups and also comparing genetic similarities and differences across thousands of genes.2. I will aim to develop useful ways to combine this information to subgroup people with joint injury, for example picking out individuals at particular risk or those with markers that mean particular treatments may work better for them. This includes looking at the presence of blood in the joint and whether we can develop it as an accurate and useful test to assess risk. Related to this, I will use scans including MRI to measure blood or look for other features that predict outcome.3. I will aim to drive clinical trials of new interventions, particular drugs, in PTOA and in idiopathic OA. This will look at what is deliverable and acceptable to those taking part in trials (individuals with joint injury and with knee OA and their healthcare professionals), work with the international community including stakeholders like drug companies to develop guidance for trials in the area and enable us to select at least one new intervention to take forward to testing in a full trial (which will be funded by other means).A predictive test or tool which rates an individual's risk of OA would have a number of advantages: to the individual, enabling lifestyle planning and decisions around treatments; and to drive clinical trials of new treatments in this area - picking out those at highest risk or most likely to respond would make trials more deliverable and acceptable. It may also give us more accurate answers from smaller numbers. This work aims to speed up the development of new treatments for those with PTOA and potentially also idiopathic OA. Given the high and growing numbers with OA, any innovation is likely to benefit healthcare and society.

骨关节炎（OA）是关节炎最常见的形式，影响英国850万人。它的相关医疗预算估计为20亿英镑，社会成本要高得多。除了昂贵的关节置换术，我们目前还没有预防、减缓或治愈OA的药物治疗。膝关节损伤是未来膝关节OA的最大风险因素。大约一半的膝关节损伤患者（如韧带撕裂）会发展为OA;手术治疗损伤并不能降低这种风险。这种类型的OA被称为“创伤后骨关节炎”（PTOA）。PTOA患者通常较年轻，但我们不知道这种形式是否与“普通”（特发性）OA相同。研究关节损伤和PTOA患者提供了一个无与伦比的机会来了解导致OA的过程，并旨在通过测量和靶向这些过程来预防OA。到目前为止，我们已经表明，膝关节对损伤的炎症反应在人与人之间差异很大。这种最初的“关节损伤反应”与OA相关的后期症状有关。最初的发现是，膝关节液（滑液）中的两个代表性“标志物”，即受伤时关节内血液增加和液体增加，都是膝关节损伤患者预后不良的标志物。在英国生物银行的工作中，我们发现受伤时年龄较大和女性也会增加膝关节损伤后OA的风险。已知的“OA基因”并没有特别增加这种风险（尽管我们在完成更多的研究之前无法确定）。我们还发现了一个可能的新基因关联（以前没有看到与OA），这将需要进一步测试。我的总体目标是开发新的知识，将有利于患者和NHS，主要目的是能够运行临床试验的新疗法，寻求预防OA。这些试验重点关注那些经历过膝关节损伤的人或其他发生膝关节OA的高危人群。有三个主要目的和相关目标：1。我将通过观察这两组个体关节液中的许多（数千）蛋白质，并比较数千个基因的遗传相似性和差异性，来展示PTOA和特发性OA的相似性或不同性。我将致力于开发有用的方法，将这些信息联合收割机与关节损伤的亚组人群相结合，例如挑选出具有特定风险的个体或那些具有标志物的个体，这些标志物意味着特定的治疗可能对他们更有效。这包括观察关节中血液的存在，以及我们是否可以将其开发为评估风险的准确和有用的测试。与此相关，我将使用包括MRI在内的扫描来测量血液或寻找预测结果的其他特征。3.我将致力于推动新干预措施的临床试验，特别是PTOA和特发性OA的药物。这将着眼于什么是可交付的和可接受的那些参加试验（关节损伤和膝关节OA患者及其医疗保健专业人员），与包括制药公司在内的利益相关者在内的国际社会合作，制定该领域试验的指导方针，使我们能够选择至少一种新的干预措施，以进行全面试验预测性测试或评估个人OA风险的工具将具有许多优势：对个人而言，能够进行生活方式规划和治疗决策;并推动这一领域新疗法的临床试验--挑选出风险最高或最有可能起作用的药物将使试验更容易交付和接受。它也可以从较小的数字中给我们更准确的答案。这项工作旨在加速开发针对PTOA和潜在的特发性OA患者的新治疗方法。考虑到OA患者的数量越来越多，任何创新都可能使医疗保健和社会受益。