CHECKPOINT: Finding immune & metabolic pathways to SMI

检查点：寻找免疫力

• 批准号: MR/Z50354X/1
• 负责人: Edward Bullmore
• 金额: $ 476.7万
• 依托单位: University of Cambridge
• 依托单位国家: 英国
• 项目类别: Research Grant
• 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%2FZ50354X%2F1
• 关键词: CHECKPOINT; Finding; immune; metabolic; pathways

What? CHECKPOINT will be a national and international hub of scientists and people with lived experience (PWLE) working openly and transparently together. We will unlock the unprecedented opportunity provided by big data and advanced computational analysis to find causal pathways that connect physical and mental health. This will accelerate development of personalised treatments that work by targeting the immune and metabolic causes of severe mental illness (SMI) in those patients most likely to benefit.Why? There is growing evidence through research that people with SMI can also have unusual changes in their immune system, like inflammation, and have increased risk of metabolic disorders, like obesity, due to unusual fat and sugar metabolism in the body. These links between physical and mental health indicate a new opportunity to understand, treat and prevent SMI and make significant advances on a science-based approach for precision psychiatry. The fundamental challenge now is to discover how immune and metabolic factors can actually cause SMI. If we can find these causal links, from the body through the brain to the mind, we can develop new drug treatments for SMI that work by targeting the immune or metabolic systems. We can use blood tests, brain scans and other biomarkers to identify which patients will benefit from personalised treatment. We can advise patients more precisely about which lifestyle adjustments, such as eating a different diet or being more active, are most likely to be beneficial for their mental health.How? CHECKPOINT will address these key challenges by bringing together a diverse group of investigators with inter-disciplinary scientific expertise, and PWLE, based at 5 centres of excellence in the UK and Europe. The team will use large amounts of existing data, from genetic studies of SMI and other sources, in three main ways.The first way is called target triangulation. We will use genetic analysis to screen a large number of molecules and cells in the immune and metabolic systems that could be targeted for treatment. We expect to find a small proportion of screened targets will have a causal role in disorders like schizophrenia, or across a range of SMI disorders. Targets that pass preliminary screening will be prioritized for deeper analysis of genetic, clinical and longitudinal follow-up data, to find the top few immune or metabolic targets for SMI by triangulating multiple convergent lines of evidence for causality.The second way is called biomarker innovation. We will analyse blood immune cells collected from patients with psychosis and starting treatment with anti-psychotic drugs. We will also analyse brain MRI scans, and design video games to measure thinking and behaviour in young people. We will identify which of these potential biomarkers could be used to identify the patients with SMI most likely to respond to treatments targeting the immune or metabolic systems.The third way is called therapeutic personalisation. We will find which new drugs or already-licensed medications are most likely to be effective in treating the immune or metabolic causes of SMI. Scientists and PWLE will also co-produce two projects: (i) to develop better tools for predicting adverse physical health co-occurring with mental health, especially due to anti-psychotic drug treatment; and (ii) to build evidence from health data and interviews with patients about which lifestyle interventions are most likely to be effective and accessible for people with SMI.

- 你说什么？KNOKPOINT将成为科学家和有生活经验的人（PWLE）的国家和国际中心，公开透明地共同工作。我们将利用大数据和先进的计算分析提供的前所未有的机会，找到连接身心健康的因果途径。这将加速个性化治疗的发展，通过针对那些最有可能受益的患者的严重精神疾病（SMI）的免疫和代谢原因来发挥作用。为什么？越来越多的研究证据表明，SMI患者的免疫系统也会发生异常变化，如炎症，并且由于体内不寻常的脂肪和糖代谢，导致代谢紊乱的风险增加，如肥胖。身体和心理健康之间的这些联系表明了理解，治疗和预防SMI的新机会，并在以科学为基础的精确精神病学方法方面取得了重大进展。现在的根本挑战是发现免疫和代谢因素如何实际导致SMI。如果我们能找到这些因果关系，从身体到大脑到心灵，我们就可以开发出针对免疫或代谢系统的SMI的新药物治疗方法。我们可以使用血液测试，脑部扫描和其他生物标志物来确定哪些患者将从个性化治疗中受益。我们可以更准确地告诉患者哪些生活方式的调整，比如改变饮食习惯或多运动，最有可能有益于他们的心理健康。BARKPOINT将通过汇集具有跨学科科学专业知识的多元化研究人员团队以及位于英国和欧洲的5个卓越中心的PWLE来应对这些关键挑战。研究小组将通过三种主要方式利用SMI基因研究和其他来源的大量现有数据。我们将使用遗传分析来筛选免疫和代谢系统中的大量分子和细胞，这些分子和细胞可以作为治疗的目标。我们希望发现一小部分筛选的靶点在精神分裂症等疾病或一系列SMI疾病中具有因果作用。通过初步筛选的靶点将被优先用于更深入的遗传学、临床和纵向随访数据分析，通过对因果关系的多条趋同证据线进行三角测量，找到SMI的前几个免疫或代谢靶点。第二种方式称为生物标志物创新。我们将分析从精神病患者中收集的血液免疫细胞，并开始使用抗精神病药物治疗。我们还将分析大脑MRI扫描，并设计视频游戏来衡量年轻人的思维和行为。我们将确定哪些潜在生物标志物可用于识别最有可能对针对免疫或代谢系统的治疗产生反应的重度精神分裂症患者。第三种方式称为治疗个性化。我们将发现哪些新药或已经获得许可的药物最有可能有效治疗SMI的免疫或代谢原因。科学家和PWLE还将共同制作两个项目：（i）开发更好的工具来预测不良的身体健康与心理健康的共同发生，特别是由于抗精神病药物治疗;（ii）从健康数据和与患者的访谈中建立证据，了解哪些生活方式干预最有可能对SMI患者有效和可获得。