Sampling and biomarker OPtimisation and Harmonisation In ALS and other motor neuron diseases (SOPHIA)

ALS 和其他运动神经元疾病的采样和生物标志物优化与协调 (SOPHIA)

• 批准号: MR/K000039/1
• 负责人: Pamela Shaw
• 金额: $ 17.99万
• 依托单位: University of Sheffield
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2012
• 资助国家: 英国
• 起止时间: 2012 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FK000039%2F1
• 关键词: Sampling; biomarker; OPtimisation; Harmonisation; ALS

Amyotrophic Lateral Sclerosis (ALS) is one of the most devastating diseases in neurology affecting some 50,000 individuals at any time in Europe, and causing around 10,000 deaths each year. The main clinical features are weakness and wasting of muscles, but dementia may also occur. ALS represents a good model for study of all neurodegenerative conditions, as it has a characteristic phenotype, rapid progression and the correlation between diagnosis during life and autopsy diagnosis is close to 100%. However, validated neurochemical biomarkers for monitoring disease activity, for generating earlier diagnoses and for defining prognosis are lacking. Active European collaborations are in place for harmonizing clinical datasets, neuroimaging and neuropathology protocols. A preliminary strategy for harmonization of biological and tissue samples has been established. Standardized protocols for clinical data and sample collection are now urgently required for optimization and harmonization of biomarker development. The overall aim of this proposal is to provide a common European strategy for the prioritization and selection of candidate biomarker domains for optimization and harmonization. This will in turn provide a long-term platform by which existing collaborative structures that are relevant to neurodegenerative disease biomarkers (including academic initiatives, co-funding strategies, biobanks, industrial efforts, private-public alliances) are integrated within an inclusive web-based virtual biobank. Samples and clinical/imaging/neurophysiologic and neuropathological datasets provided by participating members can then be optimally utilized to enable state of the art collaborative analyses.The established platform will also act as an important communication channel between this consortium and the rest of the ALS/Neurodegeneration field to ensure that the optimization efforts are in line with the whole ALS/ND field, to avoid duplication of work, and to ensure better acceptance and utilization of the project results by all stakeholders. Ultimately, the platform will be used to disseminate the results to the whole ALS/Neurodegeneration field, and will act as a permanent Interactive European ALS biomarker platform for researchers to optimize/harmonize novel biomarkers using an established pan-European ALS methodology. The platform will also allow interaction with those of other cognate groups (e.g the NEALS group within the US) and with patient groups and other relevant stakeholders.

肌萎缩侧索硬化症（ALS）是神经病学中最具破坏性的疾病之一，在欧洲任何时候都影响着大约50，000人，每年造成大约10，000人死亡。主要临床特征是肌肉无力和萎缩，但也可能发生痴呆。ALS代表了研究所有神经退行性疾病的良好模型，因为它具有特征性表型，快速进展，并且生命期间诊断与尸检诊断之间的相关性接近100%。然而，缺乏有效的神经化学生物标志物，用于监测疾病活动，用于产生早期诊断和用于定义预后。积极的欧洲合作已经到位，以协调临床数据集，神经成像和神经病理学协议。已经制定了统一生物和组织样本的初步战略。现在迫切需要临床数据和样本收集的标准化方案，以优化和协调生物标志物的开发。该提案的总体目标是提供一个共同的欧洲战略，用于优化和协调候选生物标志物领域的优先级和选择。这反过来将提供一个长期平台，通过该平台，与神经退行性疾病生物标志物相关的现有合作结构（包括学术倡议，共同资助策略，生物库，工业努力，公私联盟）被整合到一个包容性的基于网络的虚拟生物库中。由参与成员提供的样本和临床/成像/神经生理学和神经病理学数据集可以被最佳地利用，以实现最先进的协作分析。建立的平台也将作为该联盟与ALS/神经退行性疾病领域其他成员之间的重要沟通渠道，以确保优化工作与整个ALS/ND领域保持一致，避免重复工作，并确保所有利益攸关方更好地接受和利用项目成果。最终，该平台将用于将结果传播到整个ALS/神经变性领域，并将作为研究人员使用既定的泛欧ALS方法优化/协调新型生物标志物的永久性交互式欧洲ALS生物标志物平台。该平台还将允许与其他同源团体（例如美国的NEALS团体）以及患者团体和其他相关利益相关者进行互动。

项目成果

Sequestration of multiple RNA recognition motif-containing proteins by C9orf72 repeat expansions.

• DOI: 10.1093/brain/awu120
• 发表时间: 2014-07
• 期刊: Brain : a journal of neurology
• 作者: Cooper-Knock J;Walsh MJ;Higginbottom A;Robin Highley J;Dickman MJ;Edbauer D;Ince PG;Wharton SB;Wilson SA;Kirby J;Hautbergue GM;Shaw PJ
• 通讯作者: Shaw PJ

The genetics of amyotrophic lateral sclerosis: current insights.

• DOI: 10.2147/dnnd.s84956
• 发表时间: 2016
• 期刊: Degenerative neurological and neuromuscular disease
• 影响因子: 4
• 作者: Alsultan AA;Waller R;Heath PR;Kirby J
• 通讯作者: Kirby J

Case report of concurrent Fabry disease and amyotrophic lateral sclerosis supports a common pathway of pathogenesis.

• DOI: 10.3109/21678421.2016.1170150
• 发表时间: 2016-10
• 期刊: Amyotrophic lateral sclerosis & frontotemporal degeneration
• 影响因子: 2.8
• 作者: Beer AM;Cooper-Knock J;Fletcher S;Brown-Wright SH;Nandakumar TP;Shaw PJ
• 通讯作者: Shaw PJ

Lysosomal and phagocytic activity is increased in astrocytes during disease progression in the SOD1 (G93A) mouse model of amyotrophic lateral sclerosis.

• DOI: 10.3389/fncel.2015.00410
• 发表时间: 2015
• 期刊: Frontiers in cellular neuroscience
• 影响因子: 5.3
• 作者: Baker DJ;Blackburn DJ;Keatinge M;Sokhi D;Viskaitis P;Heath PR;Ferraiuolo L;Kirby J;Shaw PJ
• 通讯作者: Shaw PJ

C9ORF72 GGGGCC Expanded Repeats Produce Splicing Dysregulation which Correlates with Disease Severity in Amyotrophic Lateral Sclerosis.

• DOI: 10.1371/journal.pone.0127376
• 发表时间: 2015
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Cooper-Knock J;Bury JJ;Heath PR;Wyles M;Higginbottom A;Gelsthorpe C;Highley JR;Hautbergue G;Rattray M;Kirby J;Shaw PJ
• 通讯作者: Shaw PJ