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MICA: Dementias Platform UK 2 - Integrated Dementia Experimental Medicine

MICA：英国痴呆症平台 2 - 综合痴呆症实验医学

基本信息

批准号：
MR/T033371/1
负责人：
John Gallacher
金额：
$ 1649.02万
依托单位：
University of Oxford
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2021
资助国家：
英国
起止时间：
2021 至无数据
项目状态：
未结题

来源：
https://gtr.ukri.org/projects?ref=MR%2FT033371%2F1
关键词：
MICA Dementias Platform UK Integrated

项目摘要

DPUK is a public-private partnership to accelerate the development of new treatments for dementia. Since inception (2014) DPUK has increased the UK capacity for dementia research through infrastructure development and strategic data collection, leveraging a further £74.4m for dementia research. The second phase of DPUK (DPUK2) focuses on developing UK capacity for dementia experimental medicine. A major challenge in developing new treatments is understanding the mechanisms through which a drug might operate. This involves precision studies where individuals of known vulnerability to specific causes of dementia are recruited to studies of cause-specific mechanistic pathways. These studies are very difficult to do as they require detailed assessment of volunteers before the study begins and standardising all the procedures in centres across the UK. These studies are also high risk in that there is no guarantee of success.DPUK2 addresses these issues head-on at two levels. First it uses the UK's rich legacy in population cohort studies to identify suitable volunteers by using and enhancing existing cohort data. Second it creates a pre-competitive environment that brings together industry, academic and third-sector entities into partnership. This not only shares the costs and risks of experimental medicine (EM) studies, it also shares the benefits amongst a wider spread of stakeholders, each able to exploit the findings. DPUK2 does this through 3 inter-dependent work-streams.1. The Data Portal (DP): The DP is a world leading end-to-end dementia focused data management solution. It enables large and complex datasets to be accessed remotely from around the globe without compromising data security. The DP is being developed in partnership with Health Data Research UK (HDR UK) so that we can maximise the data available to dementia research. The DP is used to manage all the data and information systems necessary for conducting precision studies. It brings large and complex datasets together in order to test new ideas; it manages personal information securely to enable recruitment to precision studies; it manages many types of data so that genetics, brain imaging, cognitive performance; and questionnaire data can all be analysed together.2. The Trials Delivery Framework (TDF): The TDF is the vehicle that enables the DPUK2 experimental medicine programme to be efficient. The TDF organises our Clinical Studies Register (CSR) through which cohort members can volunteer for experimental medicine studies. The CSR allows us to contact members to enrich their data in terms of background information, cognitive testing, and where necessary genetics. As part of the CSR, and in partnership with the Alzheimer's Society, we have a PPI programme to understand what best practice is in terms if recruitment to experimental medicine studies. The TDF also enables us to identify centres of excellence across the UK for conducting experimental studies rigorously. This not only assures data quality, but also means that volunteers do not have to travel too far to participate.3. The EM Incubator: The incubator is where our partners meet to plan and execute the experimental medicine programme. It has three themes; the first is Vascular Health. This is important because so many factors that affect the heart also affect the brain. If any area is likely to have drugs that already exist and could be re-purposed for dementia, this is it.The second theme is Synaptic Health. Here we investigate factors that affect the loss of neuron synapses. This is important because unlike neurons, synapses (the connections between neurons), can be generated, which is critical to learning and maintaining memory. The third area is Neuroimmunology. This is important as inflammation is a systemic problem that is known to affect the brain and might have systemic solutions, and so represents a promising area for new treatments.

DPUK是一个公私合作伙伴关系，旨在加快痴呆症新疗法的开发。自成立(2014年)以来，DPUK通过基础设施发展和战略数据收集，增加了英国痴呆症研究的能力，进一步利用7440万GB用于痴呆症研究。DPUK(DPUK2)的第二阶段侧重于发展英国痴呆症实验医学的能力。开发新疗法的一个主要挑战是了解药物可能起作用的机制。这涉及到精确研究，即将已知易患痴呆症的特定原因的个体招募到特定原因的机制路径的研究中。这些研究非常困难，因为它们需要在研究开始之前对志愿者进行详细的评估，并将英国各地中心的所有程序标准化。这些研究也是高风险的，因为不能保证成功。DPUK2从两个层面正面解决这些问题。首先，它利用英国在人口队列研究方面的丰富遗产，通过使用和增强现有的队列数据来确定合适的志愿者。其次，它创造了一种竞争前的环境，将行业、学术和第三部门实体聚集在一起，形成伙伴关系。这不仅分担了实验医学(EM)研究的成本和风险，还让更广泛的利益相关者分享了好处，每个利益相关者都能够利用这一发现。DPUK2通过3个相互依赖的工作流来实现这一点。数据门户(DP)：DP是世界领先的端到端痴呆症数据管理解决方案。它支持从全球远程访问大型且复杂的数据集，而不会影响数据安全性。DP是与英国健康数据研究(HDR UK)合作开发的，这样我们就可以最大限度地利用可用于痴呆症研究的数据。DP用于管理进行精度研究所需的所有数据和信息系统。它将庞大而复杂的数据集汇集在一起，以测试新的想法；它安全地管理个人信息，以便能够从招募到精确研究；它管理多种类型的数据，以便可以将遗传学、大脑成像、认知表现和问卷数据全部分析在一起。试验交付框架(TDF)：TDF是使DPUK2实验医学计划高效的载体。TDF组织了我们的临床研究登记(CSR)，通过该登记，队列成员可以自愿参加实验医学研究。CSR允许我们联系成员，以丰富他们在背景信息、认知测试以及必要时的遗传学方面的数据。作为CSR的一部分，并与阿尔茨海默氏症协会合作，我们有一个PPI方案，以了解如果招募到实验医学研究方面的最佳做法是什么。TDF还使我们能够在英国各地找到严格进行实验研究的卓越中心。这不仅保证了数据质量，还意味着志愿者不必走太远的路就能参与。EM孵化器：孵化器是我们的合作伙伴计划和执行实验医学计划的地方。它有三个主题；第一个是血管健康。这一点很重要，因为许多影响心脏的因素也会影响大脑。如果有任何地区可能有已经存在的药物，并可能被重新用于治疗痴呆症，这就是它。第二个主题是突触健康。在这里，我们研究影响神经元突触丢失的因素。这一点很重要，因为与神经元不同，突触(神经元之间的连接)可以产生，这对学习和保持记忆至关重要。第三个领域是神经免疫学。这一点很重要，因为炎症是一种已知的影响大脑的系统性问题，可能有系统性的解决方案，因此代表着一个有希望的新治疗领域。

项目成果

期刊论文数量（10）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Lifestyle Score and Risk of Hypertension in the Airwave Health Monitoring Study of British Police Force Employees.

在英国警察部队的Airwave健康监测研究中，生活方式评分和高血压风险。

DOI：
10.3390/ijerph20054029
发表时间：
2023-02-24
期刊：
INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH
影响因子：
0
作者：
Aljuraiban, Ghadeer S;Gibson, Rachel;Chan, Doris S M;Elliott, Paul;Chan, Queenie;Griep, Linda M Oude
通讯作者：
Griep, Linda M Oude

Vasculocentric Axonal NfH in Small Vessel Disease.

小血管疾病中的血管中心轴突NFH。

DOI：
10.1093/jnen/nlab134
发表时间：
2022-02-24
期刊：
Journal of neuropathology and experimental neurology
影响因子：
3.2
作者：
Anad A;Barker MK;Katanga JA;Arfanakis K;Bridges LR;Esiri MM;Isaacs JD;Prpar Mihevc S;Pereira AC;Schneider JA;Hainsworth AH
通讯作者：
Hainsworth AH

Changes in NfL Plasma Levels and Association with Cognitive and Imaging Markers of Alzheimer's Disease

NfL 血浆水平的变化及其与阿尔茨海默氏病认知和影像标志物的关联