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) 是最常见的关节炎，影响英国 850 万人，相关医疗预算估计为 20 亿英镑，除了昂贵的关节置换术之外，我们目前没有药物治疗。预防、减缓或治愈 OA。膝关节损伤是未来膝关节 OA 的最大危险因素。大约一半患有韧带撕裂等膝关节损伤的人会患上 OA；手术治疗并不能降低这种类型的风险。 OA 被称为“创伤后骨关节炎”(PTOA)，患有 PTOA 的人通常比较年轻，但我们不知道这种形式是否与研究患有关节损伤和患有关节炎的“普通”（特发性）OA 相同。 PTOA 为了解导致 OA 的过程提供了无与伦比的机会，并通过测量和针对这些过程来预防 OA。到目前为止，我们已经表明，膝关节对损伤的炎症反应在不同时期存在显着差异。这种最初的“关节损伤反应”与随后的 OA 相关症状有关。初步发现，膝关节液（滑液）中的两个代表性“标志物”——受伤时关节内的血液增加和液体增加都起作用。作为膝关节损伤患者预后较差的标志，我们在英国生物银行的研究中发现，受伤时年龄较大和女性也会增加膝关节损伤后患 OA 的风险。已知的“OA 基因”并不会特别增加这种风险。 （尽管我们不能确定，直到我们我们还发现了一个可能的新基因关联（以前未曾在 OA 中发现过），这需要进一步测试。我的总体目标是开发有利于患者和 NHS 的新知识，其主要目标是能够进行旨在预防 OA 的新疗法的临床试验。这些试验重点关注经历过膝关节损伤的人或其他发生膝 OA 的高风险人群。有以下三个主要目的和相关目标：1。我的目的是展示 PTOA 和特发性 OA 是通过观察这两组个体关节液中的许多（数千）种蛋白质，并比较数千个基因的遗传相似性和差异。2。患有关节损伤的人，例如挑选出具有特定风险的人或具有意味着特定治疗可能对他们更有效的标记的人，这包括观察关节中是否存在血液以及我们是否可以将其开发为准确且有用的测试。评估与此相关的风险。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. 我的目标是推动针对 PTOA 和特发性 OA 的新干预措施（特别是药物）的临床试验。参加试验（患有关节损伤和膝关节骨关节炎的个体及其医疗保健专业人员），与包括制药公司等利益相关者在内的国际社会合作，制定该领域试验的指南，并使我们能够选择至少一种新的干预措施来推进进行全面测试评估个人骨关节炎风险的预测测试或工具有许多优点：对个人而言，可以制定生活方式并做出治疗决策，并推动新疗法的临床试验；在这一领域 - 挑选出那些风险最高或最有可能做出反应的人将使试验更加可行和可接受，这也可能为我们提供更准确的答案，这项工作旨在加快针对 PTOA 患者的新疗法的开发。也可能是特发性 OA。 OA 患者人数不断增加，任何创新都可能造福医疗保健和社会。