Improved Outcome Assessments in Adrenomyeloneuropathy

改进肾上腺脊髓神经病的结果评估

基本信息

批准号：
10442671
负责人：
Adeline Lucie Vanderver
金额：
$ 16.56万
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 2024-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10442671
关键词：
Address Adrenoleukodystrophy Adrenomyeloneuropathy Adult Advocacy Affect Ataxia Awareness Basic Science Biochemical Markers Bladder Dysfunction Brain Caring Cerebrum Childhood Clinical Research Clinical Trials Clinical Trials Network Companions Data Development Diagnostic Disease Disease Progression Equilibrium Federal Government Female Functional disorder Future Gait Gait abnormality General Hospitals Genes Heterozygote Home Individual Institutes Intervention Intestines Knowledge Laboratories Letters Link Massachusetts Measures Motion Mutation Nature Neonatal Screening Nervous system structure Neurologic Outcome Outcome Assessment Outcome Measure Pathogenicity Pathology Patient Outcomes Assessments Patients Performance Peripheral Nerves Peripheral Nervous System Diseases Persons Phenotype Population Reproducibility Research Subjects Sample Size Sensory Ataxias Series Site Spastic Paraparesis Spinal Cord Spinal Cord Column Spinal Cord Diseases System Technology Testing Therapeutic Time Validation Validity and Reliability Very Long Chain Fatty Acid Walking base clinical development clinical outcome assessment clinical trial readiness disability dorsal column effectiveness testing improved improved outcome industry partner leukodystrophy male nervous system disorder novel rate of change recruit remote assessment tool treatment response walking speed wearable device

项目摘要

Abstract X-linked adrenoleukodystrophy (ALD), a debilitating neurological disorder caused by mutations in the ABCD1 gene, is one of the few leukodystrophies for which newborn screening is available and recommended by the federal government. Adult-onset Adrenomyeloneuropathy (AMN) is the most common phenotype of ALD, as adult males with pathogenic changes in ABCD1 and more than half of female ALD heterozygotes develop AMN over time. Despite advances in the treatment for the childhood onset cerebral form of ALD, no treatment is currently available for AMN. Additionally, the slow and variable rate of disease progression and lack of understanding of clinical outcome assessments (COA) hamper AMN clinical trial readiness. In order to address this critical gap in knowledge, we propose to identify novel tools for clinical outcome assessment in AMN. We collaborate with ALD Connect (see letter of support), a consortium dedicated to improving care and treatment for ALD and AMN. Together, we have established an adult AMN rating scale. Based on concurrent data collected in Project 1 that will determine the rate of change and relationships among patient reported outcomes (PRO) and COA such as walking speed, we will validate this tool and assess its use in capturing disease progression (Aim 1). Additionally, we propose to conduct studies at two expert AMN motion analysis laboratories to assess whether advanced force plate measures of ataxia are of utility as assessments in this condition (Aim 2). Finally, we have obtained pilot data showing that key metrics of ataxia, sway amplitude and gait variables, can be assessed remotely using wearable technology. We propose to assess whether wearable devices are of utility as assessments of ataxia in this condition (Aim 3). The results of this project will be vital for the facilitation of clinical studies for therapies that are currently under development for adults with AMN.

抽象的 X连锁的肾上腺素肌营养不良（ALD），这是一种由ABCD1突变引起的令人衰弱的神经系统疾病吉恩（Gene）是为数不多的白细胞营养不良之一。联邦政府。成人发作的肾上腺素肌病（AMN）是ALD的最常见表型，如成年男性在ABCD1和一半以上的雌性ALD杂合子中发生致病性变化随着时间的流逝。尽管在童年发作的治疗方面取得了进步，但没有治疗目前可用于AMN。此外，疾病进展的缓慢和可变率缺乏了解临床结果评估（COA）障碍AMN临床试验准备就绪。为了解决知识的关键差距，我们建议确定新颖的临床结果工具评估AMN。我们与Ald Connect合作（请参阅支持信），该财团致力于改善ALD和AMN的护理和治疗。我们共同建立了成人AMN评级量表。基于项目1中收集的并发数据，该数据将确定变化率和关系患者报告的结果（PRO）和COA（例如步行速度），我们将验证该工具并评估其用于捕获疾病进展（目标1）。此外，我们建议对两个专家进行研究 AMN运动分析实验室评估共济失调的先进板量度是否具有实用性作为在这种情况下的评估（AIM 2）。最后，我们获得了试点数据，显示可以使用可穿戴技术远程评估共济失调，摇摆幅度和步态变量。我们建议评估可穿戴设备是否具有效用作为在这种情况下对共济失调的评估（AIM 3）。该项目的结果对于促进目前正在下的疗法的临床研究至关重要成人AMN的发展。