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，由于脑白质缺失或缺失而影响脑白质。 髓鞘，将神经系统中的轴突隔绝的类脂膜。脑白质营养不良社区正处于 关键转折点。新的分子方法提高了对疾病的认识。同时按下键 现在，疾病有了潜在的治疗途径。在临床试验准备方面存在迫切的未得到满足的需求，以免 临床前开发的承诺无法转化为精心设计的临床试验。这一差距在 知识激励了疾病界的利益相关者。在与倡导伙伴的合作下，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)。在这项提议中，Glia-CTN将开始一段纵向的自然历史，专注于但不是 仅限于5种已准备好临床试验的脑白质营养不良症：肾上腺髓神经病(AMN)、Aicard Goutieres 综合征(AGS)、亚历山大病(AxD)、异色性脑白质营养不良症和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)注重可靠性、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病史数据。同伴 围绕新的工具和量表的项目，以定义AMN中的共济失调，新的疾病分类策略 AGS及其与疾病严重程度和生物标记物的相关性，以及GFAP周围的证据标准(胶质细胞 纤维酸性蛋白)作为AxD的生物标记物完成了提案。将对这些项目进行监督 在一个发展完善的行政单位下，包括一个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，这要归功于与参与机构分担的大量费用。 该计划的可持续性得到了强有力的职业发展和试点项目计划的补充。全 该计划的各个方面都与我们的患者倡导合作伙伴谨慎地保持一致，他们提供了有意义的 并将成为数据共享平台的利益攸关方。这些方法结合在一起，将建立一个平台 在临床科学家的密切合作下，开发脑白质营养不良的临床试验准备情况， 倡导团体和行业合作伙伴，促进该领域的变革。

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.