Building on Brains for Dementia Research (BDR): A UK Nervous Tissue Network (UKNTN) for the Twenty-first Century

近年来，在了解我们的大脑和相关神经系统如何工作方面取得了巨大进展。这些进步使我们能够在了解许多折磨人类的精神和神经疾病方面取得巨大进展，从而开发出更好的评估，诊断和治疗方法。这些进展大多来自人类疾病的动物模型研究或细胞实验室研究。这些工作需要通过对人类大脑和神经系统的研究来证实，这通常需要使用捐赠的神经组织。此外，这些知识大部分来自对患者捐赠的这种人类神经组织的直接研究，重要的是，也来自健康人。最近的技术进步使我们能够采用新的方法来研究这些疾病。然而，这些技术需要人类神经组织，由于不同的原因，目前还不能广泛获得，例如难以从患有精神疾病的人那里获得捐赠，从大脑外部获取组织的问题以及需要获得更多的活神经组织（来自大脑手术后捐赠的组织）。该提案回应了MRC的愿望，即通过在英国各地建立一个专家中心网络来满足这一重要需求，这些中心将共同努力做到这一点。我们将把位于纽卡斯尔、布里斯托、伦敦国王学院、牛津和曼彻斯特的五个人类神经组织库和位于剑桥的五个神经组织研究专家中心联合起来，建立联合王国神经组织网络伦敦大学学院（干细胞研究所）（痴呆症研究所），国王学院伦敦（MRC神经发育障碍中心）、牛津（英国痴呆症平台）和埃克塞特（复杂疾病表观遗传学）。这五个组织库已经作为痴呆症研究大脑（BDR）网络的一部分合作，并已经共享过程，组织和数据，并免费提供给研究人员。我们将通过增加这五个专家中心，并利用他们的专业知识为研究人员提供新类型的组织和数据，来扩展这种共享工作，从而发展UKNTN。我们将通过八个工作包来实现这一目标。工作包1（WP 1）将招募所有年龄和种族的精神和神经疾病患者进行神经组织捐赠，并将他们的研究数据作为UKNTN的一部分。WP2将获得血液和保护大脑的特殊液体（脑脊液）的样本，并将这些样本与临床和NHS数据以及随后捐赠的神经组织联系起来。在WP3中，我们将报告影响捐赠大脑的疾病的尸检数据，并要求捐赠者提供其他神经组织。在WP4中，我们将与患者、家属和研究人员合作，确保我们的UKNTN流程运作良好，满足每个人的需求。WP5将基于我们在BDR计划中的经验，向患者，护理人员和研究人员宣传UKNTN及其工作。WP6将为英国各地的研究人员提供手术中新鲜捐赠的脑组织，并与从事这项研究的英国中心建立联系，以分享专业知识和简化研究方案。WP7有四个主要部分。成纤维细胞将在纽卡斯尔从新捐赠的组织中生长，干细胞将在剑桥从这些细胞中培养，迷你脑（脑类器官）将在伦敦从选定的干细胞中生长，遗传数据将在埃克塞特获得并与所有这些联系起来。最后，WP8将汇集所有UKNTN的数据，并将其与匿名的NHS临床数据联系起来，并通过一个已建立的单一安全访问点向研究人员提供这些数据。在此试点之后，我们将通过邀请其他组织库和学术神经科学中心加入UKNTN来扩大网络，所有人都将使用UKNTN的既定标准和实践进行合作。

Huge advances have been made in recent years in understanding how our brain and the related nervous system works. Such advances have enabled us to make great progress in learning about the many mental and neurological illnesses that afflict humans so better methods for assessing, diagnosing and treating them can be developed. A lot of this progress has come from studies of animal models of human diseases or from laboratory studies of cells. Such work needs to be confirmed by studies of the human brain and nervous system and this usually requires using donated nervous tissue. In addition, much of this learning has come from direct studies of such human nervous tissue donated by patients and, importantly, by healthy people too. Recent technological advances now enable us to carry out new methods of studying these diseases. However, these technologies require human nervous tissue which is not currently widely available for different reasons, such as the difficulty in obtaining donations from people with mental illnesses, problems with acquiring tissue from outside the brain and the need to obtain more living nervous tissue (derived from tissue donated following surgery on the brain). This proposal responds to the MRC's desire to meet this important need by creating a network of expert centres across the UK who will work together to do this. We will establish the United Kingdom Nervous Tissue Network (UKNTN) by bringing together five human nervous tissue banks at Newcastle, Bristol, Kings College London, Oxford and Manchester and five expert centres in nervous tissue research at Cambridge (Stem Cells Institute), University College London (Dementia Research Institute), Kings College London (MRC Centre for Neurodevelopmental Disorders), Oxford (Dementias Platform UK) and Exeter (Complex Disease Epigenetics). The five tissue banks already work together as part of the Brains for Dementia Research (BDR) network and already share processes, tissue and data and make this freely available to researchers. We will develop the UKNTN by extending this shared working by adding these five expert centres and by using their expertise to make new types of tissue and data available to researchers. We will do this with eight work packages.Work package 1 (WP1) will recruit people with mental and neurological illnesses of all ages and ethnicities for nervous tissue donation and use their research data as part of UKNTN. WP2 will obtain samples of blood and the special fluid (cerebral spinal fluid) which protects the brain and link these to clinical and NHS data and later to donated nervous tissue. In WP3 we will report autopsy data on the diseases affecting the donated brains and ask donors for other nervous tissue too. In WP4 we will work with patients and families and researchers to make sure our UKNTN processes work well and meet the needs of everyone. WP5 will build on our experience in the BDR programme to publicise the UKNTN and its work to patients, carers and researchers. WP6 will make freshly donated brain tissue from surgery available for novel studies by researchers across the UK and establish links with UK centres doing this research to share expertise and standardise research protocols. WP7 has four linked main parts. Fibroblast cells will be grown at Newcastle from newly donated tissue, stem cells will be developed from these at Cambridge, mini-brains (cerebral organoids) will be grown from selected stem cells in London and genetic data will be acquired and linked to all this at Exeter. Finally WP8 will bring together all of UKNTN data and link it to anonymised NHS clinical data and make this available to researchers via an established single secure point of access.After this pilot we will enlarge the network by asking other tissue banks and academic neuroscience centres to join UKNTN and all would work together using the established standards and practices in the UKNTN.