Utility of advanced MRI and wearable technology to identify sensory motor outcome measures in leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL)

利用先进的 MRI 和可穿戴技术来确定脑干和脊髓受累以及乳酸升高 (LBSL) 的白质脑病的感觉运动结果测量

• 批准号: 10406744
• 负责人: FLORIAN S EICHLER
• 金额: $ 15.67万
• 依托单位: CHILDREN'S HOSP OF PHILADELPHIA
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-30 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10406744
• 关键词: Adrenomyeloneuropathy; Adult; Advocacy; Advocate; Affect; Alexander Disease; Ataxia; Awareness; Axon; Bioinformatics; Biological Markers; Birth; Blood; Brain; Brain Stem; Caring; Classification; Clinical; Clinical Trials Design; Clinical Trials Network; Collaborations; Collection; Communities; Companions; Computerized Medical Record; Cost Sharing; Data; Diagnosis; Disease; Documentation; Early Diagnosis; Early identification; Early treatment; Epidemiologist; Equilibrium; Etiology; Family; Foundations; Future; Gait; Gene Expression; Glial Fibrillary Acidic Protein; Health Expenditures; Health Personnel; Healthcare; Hereditary Disease; Individual; Institution; Interferons; Joints; Knowledge; Leadership; Leukoencephalopathy; Longterm Follow-up; Magnetic Resonance Imaging; Measurement; Measures; Membrane Lipids; Metachromatic Leukodystrophy; Methodology; Mission; Modeling; Molecular; Morbidity - disease rate; Motor; Myelin; Natural History; Neonatal Screening; Nervous system structure; Outcome; Outcome Measure; Pathway interactions; Patient Outcomes Assessments; Patient advocacy; Patients; Pelizaeus-Merzbacher Disease; Performance; Phase; Pilot Projects; Positioning Attribute; Program Development; Program Sustainability; Publications; Questionnaires; Rare Diseases; Recording of previous events; Reproducibility; Research; Research Personnel; Resources; Scientist; Sensory; Severity of illness; Signal Transduction; Spinal Cord; Standardization; Subgroup; Surrogate Markers; Syndrome; System; Technology; Therapeutic; Therapeutic Trials; Time; Training; Translating; base; care burden; career development; clinical care; clinical center; clinical development; clinical outcome assessment; clinical research site; clinical trial readiness; data integration; data sharing; disease classification; epidemiology study; improved; industry partner; innovation; leukodystrophy; meetings; next generation; next generation sequencing; novel; patient advocacy group; patient oriented; preclinical development; programs; prospective; pseudotoxoplasmosis syndrome; rate of change; sharing platform; tool; wearable device; white matter; working group

Abstract: Leukodystrophies are inherited diseases that affect the white matter of the brain due to the loss or absence of myelin, the lipid membrane that insulates axons in the nervous systems. The leukodystrophy community is at a key turning point. Novel molecular approaches have increased disease recognition. At the same time key disorders now have potential treatment pathways. There is urgent unmet need in clinical trial readiness, lest the promise in pre-clinical development be unable to be translated to well-designed clinical trials. This gap in knowledge has galvanized stakeholders in the disease community. In collaboration with advocacy partners, we have formed a research-based consortium, the Global Leukodystrophy InitiAtive Clinical Trials Network (GLIA-CTN). In this proposal, the GLIA-CTN will embark on a longitudinal natural history, focused on but not limited to five leukodystrophy with clinical trial readiness: Adrenomyeloneuropathy (AMN), Aicard Goutieres Syndrome (AGS), Alexander Disease (AxD), Metachromatic Leukodystrophy and Pelizaeus Merzbacher Disease. Approaches will include Clinical Outcome Assessments (COA) and Patient Reported Outcomes (PRO) with a focus on reliability, reproducibility and validity. Additionally, we will develop methodology around Electronic Medical Record (EMR) extraction of natural history data for the leukodystrophies. Companion projects around novel tools and scales to define the ataxia seen in AMN, novel disease classification strategies in AGS and their correlation with disease severity and biomarkers, and evidentiary criteria around GFAP (glial fibrillary acidic protein) as a biomarker for AxD complete the proposal. Oversight for these projects will occur under a well-developed Administrative Unit which includes a Data Integration Core staffed by bioinformatics, epidemiologists and biostatisticians thanks to significant cost sharing with participating institutions. Sustainability of the program is supplemented with a strong career development and pilot project program. All aspects of the program are carefully aligned with our patient advocacy partners who have provided meaningful input and will be stakeholders in data sharing platforms. Together, these approaches will establish a platform to develop clinical trial readiness across the leukodystrophies, in close partnership between clinician scientists, advocacy groups and industry partners, enabling transformation of the field.

抽象的： 脑白质营养不良是一种遗传性疾病，由于脑白质缺失或缺失而影响大脑白质。 髓磷脂，在神经系统中隔离轴突的脂质膜。脑白质营养不良社区正处于 关键转折点。新颖的分子方法提高了疾病的识别率。同时关键 疾病现在有了潜在的治疗途径。临床试验准备方面存在迫切的未满足需求，以免 临床前开发的承诺无法转化为精心设计的临床试验。这个差距在 知识激励了疾病界的利益相关者。我们与倡导伙伴合作， 成立了一个以研究为基础的联盟，即全球脑白质营养不良启动临床试验网络 （GLIA-CTN）。在本提案中，GLIA-CTN 将着手纵向自然历史研究，重点关注但不包括 限于五种已准备好进行临床试验的脑白质营养不良：肾上腺脊髓神经病（AMN）、Aicard Goutieres 综合征 (AGS)、亚历山大病 (AxD)、异染性脑白质营养不良和 Pelizaeus Merzbacher 疾病。方法将包括临床结果评估 (COA) 和患者报告的结果 (PRO) 重点关注可靠性、再现性和有效性。此外，我们将围绕以下方面开发方法： 电子病历 (EMR) 提取脑白质营养不良的自然历史数据。伴侣 围绕定义 AMN 中出现的共济失调的新工具和量表的项目，新的疾病分类策略 AGS 及其与疾病严重程度和生物标志物的相关性，以及围绕 GFAP（神经胶质细胞）的证据标准 纤维酸性蛋白）作为 AxD 的生物标志物完成了该提案。将对这些项目进行监督 在一个完善的管理单元下，其中包括由生物信息学人员组成的数据集成核心， 流行病学家和生物统计学家得益于与参与机构的大量费用分摊。 该计划的可持续性得到了强大的职业发展和试点项目计划的补充。全部 该计划的各个方面都与我们的患者倡导合作伙伴密切配合，他们提供了有意义的帮助 投入并将成为数据共享平台的利益相关者。这些方法将共同建立一个平台 与临床科学家密切合作，为脑白质营养不良做好临床试验准备， 倡导团体和行业合作伙伴，促进该领域的转型。