MICA: Dementias Platform UK 2 - Integrated Dementia Experimental Medicine

DPUK是一个公私合作伙伴关系，旨在加速痴呆症新疗法的开发。自成立以来（2014年），DPUK通过基础设施建设和战略数据收集提高了英国痴呆症研究的能力，进一步利用7440万英镑用于痴呆症研究。DPUK的第二阶段（DPUK 2）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发挥作用的机制。这涉及精确研究，即招募已知易受痴呆症特定原因影响的个人来研究特定原因的机制途径。这些研究非常困难，因为它们需要在研究开始前对志愿者进行详细评估，并使英国各地中心的所有程序标准化。这些研究也是高风险的，因为没有成功的保证。DPUK 2在两个层面上解决了这些问题。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。第二，它创造了一个竞争前的环境，使工业、学术和第三部门实体结成伙伴关系。这不仅分担了实验医学（EM）研究的成本和风险，还在更广泛的利益相关者之间分享了利益，每个利益相关者都能够利用这些发现。DPUK 2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。它使大型和复杂的数据集可以从地球仪远程访问，而不会影响数据安全。DP正在与英国健康数据研究（HDR UK）合作开发，以便我们可以最大限度地利用痴呆症研究的数据。DP用于管理进行精密度研究所需的所有数据和信息系统。它将大型和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，以便能够招募精确的研究;它管理多种类型的数据，以便遗传学，大脑成像，认知表现;和问卷数据都可以一起分析。试验交付框架（TDF）：TDF是使DPUK 2实验医学项目有效的工具。TDF组织了我们的临床研究注册（CSR），通过该注册，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，以丰富他们的背景信息，认知测试和必要的遗传学方面的数据。作为企业社会责任的一部分，并与阿尔茨海默氏症协会合作，我们有一个PPI计划，以了解什么是最佳实践方面，如果招募到实验医学研究。TDF还使我们能够确定英国各地的卓越中心，以严格进行实验研究。这不仅保证了数据的质量，也意味着志愿者不必长途跋涉参加。3. EM孵化器：孵化器是我们的合作伙伴会面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。这很重要，因为影响心脏的许多因素也影响大脑。如果有任何领域可能有已经存在的药物，并可以重新用于痴呆症，这是它。第二个主题是突触健康。在这里，我们调查的因素，影响神经元突触的损失。这很重要，因为与神经元不同，突触（神经元之间的连接）可以产生，这对学习和维持记忆至关重要。第三个领域是神经免疫学。这一点很重要，因为炎症是一种全身性问题，已知会影响大脑，可能有全身性解决方案，因此代表了新治疗的一个有希望的领域。

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.