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 2016年，ALD被添加到推荐统一筛查小组（RUSP）中，并已被纳入。迄今为止，ALD 已在 36 个州和华盛顿特区实施，这对新生儿筛查提出了独特的挑战。虽然 cALD 和 AI 的治疗有效且可以挽救生命，但只有在出现后才能实施。就 cALD 而言，干预的窗口很窄且有限。这给疾病的最早阶段带来了一个重大挑战——通过新生儿筛查来识别男孩。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推荐的遵守情况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仪表板监测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。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在目标 2 中，我们将建立数据收集管道以建立更广泛的实施。利用 GLIA 内现有的电子健康记录计划。 CTN，我们将建立集中 ALD 监控的数据管道。我们将收集和整理数据。整个 GLIA-CTN 实施站点的预期成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 预期结果是生成建立基于证据所需的数据收集工具。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，但仍有一个该管道可以支持系统监控是否符合长期监控需求的紧急且未满足的需求。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。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测下降，一般方法可适应其他新生儿筛查。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）

Expanded phenotype of AARS1-related white matter disease.

AARS1 相关白质疾病的扩展表型。

DOI：
发表时间：
2021
期刊：
影响因子：
0
作者：
Helman, Guy;Mendes, Marisa I;Nicita, Francesco;Darbelli, Lama;Sherbini, Omar;Moore, Travis;Derksen, Alexa;Amy Pizzino;Carrozzo, Rosalba;Torraco, Alessandra;Catteruccia, Michela;Aiello, Chiara;Goffrini, Paola;Figuccia, Sonia;Smith, Desiree E
通讯作者：
Smith, Desiree E

Gross Motor Function in Pediatric Onset TUBB4A-Related Leukodystrophy: GMFM-88 Performance and Validation of GMFC-MLD in TUBB4A.

儿童 TUBB4A 相关脑白质营养不良中的粗大运动功能：GMFM-88 性能和 GMFC-MLD 在 TUBB4A 中的验证。

DOI：
发表时间：
2023-08
期刊：
影响因子：
1.9
作者：
Gavazzi, Francesco;Patel, Virali;Charsar, Brittany;Glanzman, Allan;Erler, Jacqueline;Sevagamoorthy, Anjana;McKenzie, Emma;Kornafel, Tracy;Ballance, Elizabeth;Pierce, Samuel R;Teng, Michelle;Formanowski, Brielle;Woidill, Sarah;Shults, Justine
通讯作者：
Shults, Justine

Acquisition of Developmental Milestones in Hypomyelination With Atrophy of the Basal Ganglia and Cerebellum and Other TUBB4A-Related Leukoencephalopathy.

获得髓鞘形成低下伴基底神经节和小脑萎缩以及其他 TUBB4A 相关白质脑病的发育里程碑。

DOI：
发表时间：
2021-04-12
期刊：
影响因子：
1.9
作者：
Gavazzi, Francesco;Charsar, Brittany A;Williams, Catherine;Shults, Justine;Alves, Cesar A;Adang, Laura;Vanderver, Adeline
通讯作者：
Vanderver, Adeline

Time to Transplant in X-Linked Adrenoleukodystrophy.

X连锁肾上腺脑白质营养不良症的移植时机到了。

DOI：
发表时间：
2022-04
期刊：
影响因子：
1.9
作者：
Bonkowsky, Joshua L;Wilkes, Jacob
通讯作者：
Wilkes, Jacob

Reliability of the Telemedicine Application of the Gross Motor Function Measure-88 in Patients With Leukodystrophy.

脑白质营养不良患者远程医疗应用粗大运动功能测量的可靠性 88。

DOI：
发表时间：
2021-12
期刊：
影响因子：
3.8
作者：
Gavazzi, Francesco;Adang, Laura;Waldman, Amy;Jan, Amanda K;Liu, Geraldine;Lorch, Scott A;DeMauro, Sara B;Shults, Justine;Pierce, Samuel R;Ballance, Elizabeth;Kornafel, Tracy;Harrington, Ann;Glanzman, Allan M;Vanderver, Adeline
通讯作者：
Vanderver, Adeline