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ALD Healthy Planet Project

ALD 健康星球计划

基本信息

批准号：
10851183
负责人：
FLORIAN S EICHLER
金额：
$ 51.2万
依托单位：
CHILDREN'S HOSP OF PHILADELPHIA
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-09-30 至 2025-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10851183
关键词：
Adrenal gland hypofunction Adrenoleukodystrophy Adrenomyeloneuropathy Brain imaging Cerebrum Cessation of life Child Health Childhood Clinical Clinical Research Clinical Trials Network Code Collaborations Complex Data Data Collection Disease District of Columbia Early Diagnosis Electronic Health Record Endocrinology Ensure Environment Funding Future Generations Guidelines Health Services Accessibility Healthcare Systems Infrastructure Institutional Review Boards Intervention Life Manuals Measures Medical Care Team Monitor Natural History Neonatal Screening Outcome Pediatric Hospitals Peroxisomal Disorders Phase Phenotype Philadelphia Planets Population Protocols documentation Rare Diseases Recommendation Resources Risk Safety Site System Testing Work boys dashboard data pipeline disability early screening evidence base family burden follow-up health equity improved leukodystrophy non-compliance programs screening guidelines screening panel screening program standard of care success tool

项目摘要

X-linked adrenoleukodystrophy (ALD) is a fatal peroxisomal disorder characterized by three distinct phenotypes: cerebral ALD (cALD), adrenomyeloneuropathy (AMN), and Addison’s only (adrenal insufficiency or AI). In 2016, ALD was added to the Recommended Uniform Screening Panel (RUSP), and it has been implemented to date in 36 states and Washington DC. ALD poses a unique challenge in newborn screening follow up. While treatments for cALD and AI are effective and life-saving, they are only implemented once there is evidence of disease involvement. In the case of cALD, there is a narrow window for intervention that is limited to the earliest phase of disease. This has created a major challenge—boys identified via newborn screening must be intensely followed throughout childhood by serial brain imaging and by endocrinologic testing. There is an urgent unmet need for a rigorous automated system to track compliance with recommended follow up testing. We will leverage our existing Rare Diseases Clinical Research Network (RDCRN) Global Leukodystrophy Initiative Clinical Trials Network (GLIA-CTN; U54TR002823) to deploy this system and measure its efficacy. In Aim 1, the CHOP Healthy Planets EPIC programming team, who originally developed the ALD monitoring dashboard in collaboration with the CHOP Leukodystrophy Center of Excellence will work with local EPIC programmers at Children’s Hospital of Atlanta, Stanford Children’s Health, and Kennedy Krieger Institute, sharing code and facilitating the adaptation of the CHOP system to local EPIC environments. The expected outcome is a functional ALD monitoring dashboard and an open-access manual on how this approach can be more broadly implemented to additional sites. In Aim 2, we will establish the data collection pipeline to establish data-driven monitoring guidelines. Leveraging the existing electronic health records program within the GLIA- CTN, we will establish the data pipeline for centralization of ALD-monitoring. We will collect and curate the data across the GLIA-CTN implementation sites. The expected outcome is a curated data pipeline and generation of pilot data to understand if existing monitoring guidelines are appropriate for a post newborn screening ALD population. The expected outcome is generation of data collection tool necessary to establish evidence-based post newborn screening guidelines. While the ALD field has been transformed by early detection and ground-breaking therapies, there is an urgent, unmet need for system to monitor compliance with long term monitoring needs. This pipeline can support presymptomatic natural history studies and establish standard of care monitoring guidelines that are data-driven. The proposed work is both clinically necessary and will help to support future hypothesis-driven work. This strategy has the potential to improve health equity, ensuring that decreased access to care does not equal decreased safety and monitoring. Additionally, the general approach can be adapted to other newborn screening programs and rare disorders with complex longitudinal monitoring needs.

X连锁肾上腺脑白质营养不良（ALD）是一种致命的过氧化物酶体疾病，其特征为三个不同的特征：表型：脑 ALD (cALD)、肾上腺脊髓神经病 (AMN) 和阿狄森氏病（肾上腺功能不全或人工智能）。 2016年，ALD被添加到推荐统一筛查小组（RUSP）中，并已被迄今为止已在 36 个州和华盛顿特区实施。 ALD 对新生儿筛查提出了独特的挑战跟进。虽然 cALD 和 AI 的治疗是有效且可以挽救生命的，但只有在出现问题后才能实施是疾病参与的证据。就 cALD 而言，干预窗口很窄且有限到疾病的最早阶段。这带来了一个重大挑战——通过新生儿筛查识别出男孩必须在整个童年时期密切关注连续脑成像和内分泌测试。迫切需要一个严格的自动化系统来跟踪建议的遵守情况，但这一需求尚未得到满足后续测试。我们将利用我们现有的全球罕见病临床研究网络 (RDCRN) 脑白质营养不良倡议临床试验网络（GLIA-CTN；U54TR002823）部署该系统并测量它的功效。在目标 1 中，最初开发 ALD 的 CHOP Healthy Planets EPIC 编程团队与 CHOP 脑白质营养不良中心合作的监测仪表板将与当地合作亚特兰大儿童医院、斯坦福儿童健康中心和肯尼迪克里格研究所的 EPIC 程序员，共享代码并促进 CHOP 系统适应当地 EPIC 环境。预期的成果是一个功能性 ALD 监控仪表板和一本关于如何使用此方法的开放获取手册更广泛地实施到其他站点。在目标 2 中，我们将建立数据收集管道来建立数据驱动的监测指南。利用 GLIA 内现有的电子健康记录计划 CTN，我们将建立集中化 ALD 监控的数据管道。我们将收集和整理数据跨 GLIA-CTN 实施站点。预期的结果是精心策划的数据管道和生成试点数据以了解现有监测指南是否适合新生儿后筛查 ALD 人口。预期结果是生成建立基于证据的必要数据收集工具新生儿筛查指南。虽然早期检测和突破性疗法已经改变了 ALD 领域，但仍有一个迫切需要系统来监测长期监测需求的遵守情况，但这一需求尚未得到满足。该管道可以支持症状前自然史研究并建立数据驱动的护理监测指南标准。拟议的工作在临床上是必要的，并将有助于支持未来的假设驱动的工作。这该战略有可能改善健康公平，确保获得护理的机会减少并不等于安全性和监控能力下降。此外，一般方法可以适用于其他新生儿筛查计划和具有复杂纵向监测需求的罕见疾病。

项目成果

期刊论文数量（18）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Novel biallelic variants in NRROS associated with a lethal microgliopathy, brain calcifications, and neurodegeneration.

DOI：
10.1007/s10048-022-00683-8
发表时间：
2022-04
期刊：
Neurogenetics
影响因子：
2.2
作者：
通讯作者：

Exploration of Gross Motor Function in Aicardi-Goutières Syndrome.

DOI：
10.1177/08830738231188753
发表时间：
2023-08
期刊：
Journal of child neurology
影响因子：
1.9
作者：
通讯作者：

Hepatic Involvement in Aicardi-Goutières Syndrome.

DOI：
10.1055/s-0040-1722673
发表时间：
2021-12
期刊：
Neuropediatrics
影响因子：
1.4
作者：
Gavazzi F;Cross ZM;Woidill S;McMann JM;Rand EB;Takanohashi A;Ulrick N;Shults J;Vanderver AL;Adang L
通讯作者：
Adang L

Adrenal insufficiency updates in children.

儿童肾上腺功能不全的最新进展。