The Dynamics And Clinical Relevance Of Grey Matter And Periventricular White Matter Pathology In Multiple Sclerosis

多发性硬化症灰质和脑室周围白质病理学的动态和临床相关性

基本信息

  • 批准号:
    MR/W019906/1
  • 负责人:
  • 金额:
    $ 123.81万
  • 依托单位:
  • 依托单位国家:
    英国
  • 项目类别:
    Research Grant
  • 财政年份:
    2022
  • 资助国家:
    英国
  • 起止时间:
    2022 至 无数据
  • 项目状态:
    未结题

项目摘要

About 130000 people in the UK have multiple sclerosis (MS) and, other than head injuries, it is the commonest cause of neurological disability in young adults, but we do not yet know its cause. The most obvious and most studied feature of MS is the presence of lesions in white matter (WM, the part of the brain that contains nerve fibres). WM lesions are seen where the covering (myelin) surrounding nerve fibres has been damaged or lost. They were the first feature of MS seen on brain scans, and it is now routine to look for WM lesions using magnetic resonance imaging (MRI) brain scans when making a diagnosis of MS. Their formation causes the episodes (termed relapses) of neurological symptoms that the majority of people with MS have initially, and we now have more than ten treatments available in the UK that can substantially reduce the risk of WM lesion formation and relapses. However, most people with MS eventually develop progressive disability without relapses, and the accumulation of WM lesions is only modestly related to this. We only have two treatments approved in the UK for progressive MS, and even these can only be given when there is MRI evidence for WM lesion activity or relapses. It is now thought that the loss of nerves cells is ultimately a more important cause of disability, but we do not know the main cause of nerve cell loss.About two decades ago it become clear that grey matter (GM; the part of the brain that contains nerve cells) is significantly involved in MS. With advances in MRI, it became possible to measure shrinkage of the brain, mainly due to loss of GM (which is itself due to nerve cell damage and loss), and it was found that this is more closely related to MS disability progression than WM lesion formation. However, other aspects of GM damage, for example GM lesions (which are usually more extensive than WM lesions) remained difficult to detect. Recognising this, in 2010 we began a study to develop new MRI methods to look for GM disease in MS. We recruited over 200 people, including people with relapsing-remitting and progressive forms of MS, and people with no known neurological disease. We developed methods to better see GM lesions, and also to detect GM abnormalities beyond lesions. We also showed that MS disease effects were greater towards the surface of the brain both in GM and WM. Importantly, we found that these abnormalities were not closely linked with WM lesions and were independently associated with disability. As such, they could represent important targets for treatments. However, with the resources available at the time, we were only able to assess about a third of people over about 18 months, and so could not robustly look for changes over time or determine if they were - in the longer-term - closely linked with brain atrophy and disability.The passage of a decade will have allowed changes in GM abnormalities to become clear, and their clinical significance to be more readily assessed, and so we now propose to follow up the people who took part in our original study. We will use updated MRI methods to look for GM and WM abnormalities, and specifically consider how WM and GM disease processes eventually lead to brain atrophy. We expect this work to provide valuable insights into the pathways leading to brain atrophy (and so nerve cell loss), and this should enable us to measure MS treatment effects on these pathways, rather than waiting for irreversible brain atrophy to occur. As we will use an MRI scanner similar to those already widely used in healthcare, we also expect this work to be quickly applicable in clinical trials (some of the methods we developed in our earlier study are already being used) and potentially in clinical practice.
在英国大约有13万人患有多发性硬化症(MS),除了头部受伤外,它是年轻人神经系统残疾的最常见原因,但我们还不知道其原因。多发性硬化症最明显、研究最多的特征是白质(大脑中包含神经纤维的部分)病变的存在。神经纤维周围的覆盖层(髓鞘)受损或丢失时可见WM病变。它们是多发性硬化症在脑部扫描中看到的第一个特征,现在在诊断多发性硬化症时,使用磁共振成像(MRI)脑部扫描来寻找WM病变是常规的。它们的形成导致大多数多发性硬化症患者最初出现的神经症状发作(称为复发),我们现在在英国有十多种可用的治疗方法,可以大大降低WM病变形成和复发的风险。然而,大多数MS患者最终会发展为进行性残疾而不会复发,WM病变的积累与此只有轻微的关系。在英国,只有两种治疗进展性多发性硬化症的方法被批准,即使是这些治疗方法,也只有在有MRI证据表明WM病变活动或复发时才能使用。现在人们认为,神经细胞的损失是最终导致残疾的一个更重要的原因,但我们不知道神经细胞损失的主要原因。大约20年前,人们清楚地认识到灰质(GM,大脑中含有神经细胞的部分)与MS有显著的关系。随着MRI技术的进步,人们可以测量大脑的萎缩,主要是由于GM的丢失(这本身是由于神经细胞的损伤和丢失),人们发现这与MS残疾的进展比WM病变的形成更密切相关。然而,转基因损害的其他方面,例如转基因病变(通常比WM病变更广泛)仍然难以发现。认识到这一点,我们在2010年开始了一项研究,开发新的MRI方法来寻找MS中的转基因疾病。我们招募了200多人,包括复发缓解型和进行性MS患者,以及没有已知神经系统疾病的患者。我们开发了更好地观察GM病变的方法,也可以检测病变以外的GM异常。我们还发现,在GM和WM中,MS疾病对大脑表面的影响都更大。重要的是,我们发现这些异常与WM病变没有密切联系,而是与残疾独立相关。因此,它们可以代表重要的治疗靶点。然而,凭借当时可用的资源,我们只能在大约18个月的时间里评估大约三分之一的人,因此无法强有力地寻找随着时间的变化,也无法确定它们是否与脑萎缩和残疾密切相关。十年的时间将使转基因异常的变化变得清晰,它们的临床意义也更容易评估,因此我们现在建议对参与我们最初研究的人进行随访。我们将使用最新的MRI方法来寻找GM和WM异常,并特别考虑WM和GM疾病过程最终如何导致脑萎缩。我们希望这项工作能够为导致脑萎缩(以及神经细胞损失)的途径提供有价值的见解,这应该使我们能够测量MS对这些途径的治疗效果,而不是等待不可逆转的脑萎缩发生。由于我们将使用类似于已经广泛应用于医疗保健的MRI扫描仪,我们也希望这项工作能够迅速应用于临床试验(我们在早期研究中开发的一些方法已经被使用),并有可能应用于临床实践。

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

Declan Chard其他文献

Enabling new insights from old scans by repurposing clinical MRI archives for multiple sclerosis research
通过将临床 MRI 档案重新用于多发性硬化症研究,从旧扫描中获得新的见解
  • DOI:
    10.1038/s41467-025-58274-8
  • 发表时间:
    2025-04-07
  • 期刊:
  • 影响因子:
    15.700
  • 作者:
    Philipp Goebl;Jed Wingrove;Omar Abdelmannan;Barbara Brito Vega;Jonathan Stutters;Silvia Da Graca Ramos;Owain Kenway;Thomas Rossor;Evangeline Wassmer;Douglas L. Arnold;D. Louis Collins;Cheryl Hemingway;Sridar Narayanan;Jeremy Chataway;Declan Chard;Juan Eugenio Iglesias;Frederik Barkhof;Geoff J. M. Parker;Neil P. Oxtoby;Yael Hacohen;Alan Thompson;Daniel C. Alexander;Olga Ciccarelli;Arman Eshaghi
  • 通讯作者:
    Arman Eshaghi
The influence of MOGAD on diagnosis of multiple sclerosis using MRI
MOGAD 对使用磁共振成像诊断多发性硬化的影响
  • DOI:
    10.1038/s41582-024-01005-2
  • 发表时间:
    2024-09-03
  • 期刊:
  • 影响因子:
    33.100
  • 作者:
    Ruth Geraldes;Georgina Arrambide;Brenda Banwell;Àlex Rovira;Rosa Cortese;Hans Lassmann;Silvia Messina;Mara Assunta Rocca;Patrick Waters;Declan Chard;Claudio Gasperini;Yael Hacohen;Romina Mariano;Friedemann Paul;Gabriele C. DeLuca;Christian Enzinger;Ludwig Kappos;M. Isabel Leite;Jaume Sastre-Garriga;Tarek Yousry;Olga Ciccarelli;Massimo Filippi;Frederik Barkhof;Jacqueline Palace
  • 通讯作者:
    Jacqueline Palace

Declan Chard的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

相似国自然基金

Molecular Interaction Reconstruction of Rheumatoid Arthritis Therapies Using Clinical Data
  • 批准号:
    31070748
  • 批准年份:
    2010
  • 资助金额:
    34.0 万元
  • 项目类别:
    面上项目

相似海外基金

Determination of the clinical relevance of Parkinson disease-associated intronic enhancer of the alpha-synuclein gene, in a novel mouse deletion model
在新型小鼠缺失模型中确定帕金森病相关的α-突触核蛋白基因内含子增强子的临床相关性
  • 批准号:
    10665271
  • 财政年份:
    2023
  • 资助金额:
    $ 123.81万
  • 项目类别:
The Clinical Relevance of Anthracycline-Related Cardiac Remodeling in Childhood Cancer Survivors
儿童癌症幸存者中蒽环类药物相关心脏重塑的临床意义
  • 批准号:
    10740728
  • 财政年份:
    2023
  • 资助金额:
    $ 123.81万
  • 项目类别:
Retaining relevance: extending clinical retention measures to improve their utility in describing HIV care engagement in the United States
保留相关性:扩大临床保留措施,以提高其在描述美国艾滋病毒护理参与方面的效用
  • 批准号:
    10759655
  • 财政年份:
    2023
  • 资助金额:
    $ 123.81万
  • 项目类别:
High-throughput functional analysis and clinical relevance of all possible variants of a gene
基因所有可能变异的高通量功能分析和临床相关性
  • 批准号:
    10601908
  • 财政年份:
    2023
  • 资助金额:
    $ 123.81万
  • 项目类别:
Investigation of the landscape of immunosequencing and its clinical relevance through novel immunoinformatic approaches
通过新型免疫信息学方法研究免疫测序的前景及其临床相关性
  • 批准号:
    10651683
  • 财政年份:
    2022
  • 资助金额:
    $ 123.81万
  • 项目类别:
Examining the effect and clinical relevance of targeted memory reactivation during sleep for stroke rehabilitation interventions
检查睡眠期间有针对性的记忆重新激活对中风康复干预的效果和临床相关性
  • 批准号:
    2750717
  • 财政年份:
    2022
  • 资助金额:
    $ 123.81万
  • 项目类别:
    Studentship
Evaluating the Clinical Relevance of Necroptosis in Ischemia Reperfusion Injury in Human Lung Transplants.
评估人肺移植缺血再灌注损伤中坏死性凋亡的临床相关性。
  • 批准号:
    485913
  • 财政年份:
    2022
  • 资助金额:
    $ 123.81万
  • 项目类别:
    Studentship Programs
Investigation of the landscape of immunosequencing and its clinical relevance through novel immunoinformatic approaches
通过新型免疫信息学方法研究免疫测序的前景及其临床相关性
  • 批准号:
    10446946
  • 财政年份:
    2022
  • 资助金额:
    $ 123.81万
  • 项目类别:
Mechanisms and clinical relevance of egress of low density neutrophils in postoperative patients
术后患者低密度中性粒细胞排出的机制和临床相关性
  • 批准号:
    21K20958
  • 财政年份:
    2021
  • 资助金额:
    $ 123.81万
  • 项目类别:
    Grant-in-Aid for Research Activity Start-up
Clinical relevance of glucose patterns in older adults
老年人血糖模式的临床相关性
  • 批准号:
    10577732
  • 财政年份:
    2021
  • 资助金额:
    $ 123.81万
  • 项目类别:
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了