Non-progressive congenital ataxia – advancing diagnosis to enhance chances for targeted therapy

非进行性先天性共济失调 â 提前诊断以增加靶向治疗的机会

• 批准号: 542553983
• 负责人: Dr. Tobias Bernd Ludwig Haack
• 金额: --
• 依托单位: Institut für Medizinische Genetik und angewandte Genomik
• 依托单位国家: 德国
• 项目类别: Research Grants
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/542553983?language=en
• 关键词: Non; progressive; congenital; ataxia; advancing

The general objective is to improve knowledge of non-progressive congenital (NPC) ataxia (also referred to as ataxic cerebral palsy), by investigating additional evidence to understand its origin, predict its natural history, and measure its impact. More specifically, we aim to: (i) enhance the application of clinical criteria by refining training instruments to allow a more reliable identification of patients; (ii) develop a detailed neuroimaging classification with better identification of patterns suggestive for acquired or genetic background, (iii) improve our understanding of the underlying pathophysiology and identify indicators for a genetic background, (iv) provide a comprehensive description of the functional profile, in particular cognition, (v) assess children’s quality of life and (vi) report on the contribution of the study of healthcare trajectories to a better understanding of NPC ataxia. To achieve these objectives, the ARTEMIS programme will build on three unique data sources: (i) a new cohort of children with NPC ataxia born between 2016 and 2020 and aged 5 to 8 years at data collection, to allow a complete characterisation of ataxia symptomatology, impairment profile, brain lesions, advanced genomic testing for complete genome analysis of unresolved cases, and to produce combined data on clinical features, brain images and genomic testing providing scientific evidence for a better understanding of pathogenesis, and assess the quality of life of children from their own perspective as often as possible; (ii) the largest European population-based collection on NPC ataxia (children born 1980-2015) to refine clinical criteria and definitions, syndromes and neuroimaging classifications, using syndromic disorders already collected, and systematically reanalysing MRI brain images (in particular maldevelopments beyond the cortical ones and patterns hitherto classified in a miscellaneous group), and genetic analysis results (implementing a cutting-edge pipeline for clinical interpretation of variants) available in routine care; (iii) real-world data, standardized using common data models to identify patients with NPC ataxia in electronic health records and other health data sources and investigating healthcare trajectories.Four distinct ARTEMIS outputs will be available for implementation in practice and in research on NPC ataxia (ARTEMIS cohort, a Novel evidence knowledge base tool, an Evidence presentation tool and a Training tool) and convey a common understanding of this very rare disease.

总体目标是通过调查其他证据来了解其起源，预测其自然史并测量其影响，从而提高对非进行性先天性（NPC）共济失调（也称为共济失调性脑瘫）的认识。更具体而言，我们的目标是：（i）改善训练工具，以便更可靠地识别病人，从而加强临床标准的应用;（ii）开发详细的神经影像学分类，更好地识别暗示后天或遗传背景的模式，（iii）提高我们对潜在病理生理学的理解，并识别遗传背景的指标，（iv）提供功能概况的全面描述，特别是认知，（v）评估儿童的生活质量和（vi）报告医疗保健轨迹研究对更好地理解NPC共济失调的贡献。为实现这些目标，非洲实时环境监测信息系统方案将以三个独特的数据来源为基础：（i）2016年至2020年出生的NPC共济失调儿童的新队列，数据收集时年龄为5至8岁，以完整描述共济失调的病理学特征、损伤特征、脑病变、用于未解决病例的完整基因组分析的先进基因组检测，并提供有关临床特征、脑部影像及基因测试的综合数据，为更深入了解发病机制提供科学证据，并尽可能多地从儿童本身的角度评估他们的生活质素;（ii）欧洲最大的基于人群的NPC共济失调收集（1980-2015年出生的儿童），以完善临床标准和定义，综合征和神经影像学分类，使用已经收集的综合征疾病，并系统地重新分析脑部核磁共振成像图像（特别是发育不良超出皮质和模式迄今分类在一个杂项组），和遗传分析结果（实施尖端的管道，用于变体的临床解释）可用于常规护理;（iii）真实世界数据，使用通用数据模型进行标准化，以在电子健康记录和其他健康数据源中识别NPC共济失调患者，并调查医疗保健轨迹。关于NPC共济失调（ARTEMIS队列，一个新的证据知识库工具，一个证据展示工具和一个培训工具），并传达对这种非常罕见的疾病的共同理解。