The Global Leukodystrophy Initiative Clinical Trials Network (GLIA-CTN)

摘要： 脑白质营养不良是一种遗传性疾病，由于脑白质的缺失或缺失而影响大脑的白色物质。 髓鞘，一种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一个 关键转折点新的分子方法增加了疾病识别。与此同时， 疾病现在有潜在的治疗途径。在临床试验准备方面存在迫切的未满足需求， 临床前开发的承诺无法转化为精心设计的临床试验。中的这一空白 知识激励了疾病界的利益攸关方。与倡导伙伴合作，我们 已经成立了一个以研究为基础的联盟，全球脑白质营养不良倡议临床试验网络 （GLIA-CTN）。在这项提案中，GLIA-CTN将着手进行纵向自然史研究，重点关注但不 仅限于5种已准备好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局评估（COA）和患者报告的结局 (PRO)重点是可靠性、再现性和有效性。此外，我们将围绕 脑白质营养不良自然史数据的电子病历（EMR）提取。同伴 围绕新工具和量表的项目，以定义AMN中观察到的共济失调，新疾病分类策略 AGS及其与疾病严重程度和生物标志物的相关性，以及GFAP（胶质细胞）周围的证据标准 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 在一个完善的行政单位，其中包括一个数据集成核心，由生物信息学工作人员， 流行病学家和生物统计学家，这要归功于与参与机构分摊的大量费用。 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。所有 该计划的各个方面都与我们的患者倡导合作伙伴密切合作，他们提供了有意义的 他们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， 通过临床科学家之间的密切合作， 倡导团体和行业合作伙伴，使该领域的转型。

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.