Improved Outcome Assessments in Adrenomyeloneuropathy

改进肾上腺脊髓神经病的结果评估

• 批准号: 10675469
• 负责人: Adeline Lucie Vanderver
• 金额: $ 16.55万
• 依托单位: CHILDREN'S HOSP OF PHILADELPHIA
• 依托单位国家: 美国
• 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/10675469
• 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; Collaborations; Companions; Data; Dedications; Development; Disease; Disease Progression; Equilibrium; Federal Government; Female; Functional disorder; Future; Gait; Gait abnormality; General Hospitals; Genes; Heterozygote; Home; Individual; Intervention; Intestines; Knowledge; Laboratories; Letters; Link; Massachusetts; Measures; Motion; Mutation; Nature; Neonatal Screening; Nervous System; Neurologic; Outcome; Outcome Assessment; Outcome Measure; Pathogenicity; Pathology; Patient Outcomes Assessments; Patients; Performance; Peripheral Nerves; Peripheral Nervous System Diseases; Persons; Phenotype; Population; Recommendation; 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; Very Long Chain Fatty Acid; Walking; 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; technology platform; tool; treatment response; walking speed; wearable device

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连锁肾上腺脑白质营养不良 (ALD)，一种由 ABCD1 突变引起的衰弱性神经系统疾病 基因，是为数不多的可进行新生儿筛查并被世界卫生组织推荐的脑白质营养不良之一。 联邦政府。成人发病的肾上腺脊髓神经病 (AMN) 是 ALD 最常见的表型， ABCD1 致病性改变的成年男性和超过一半的女性 ALD 杂合子出现 AMN 随着时间的推移。尽管儿童期发病的大脑型 ALD 的治疗取得了进展，但尚无治疗方法 目前可用于 AMN。此外，疾病进展速度缓慢且多变，而且缺乏 对临床结果评估 (COA) 的了解阻碍了 AMN 临床试验的准备工作。 为了解决这一知识上的关键差距，我们建议寻找临床结果的新工具 AMN 中的评估。我们与 ALD Connect 合作（参见支持信），这是一个致力于 改善 ALD 和 AMN 的护理和治疗。我们共同制定了成人 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以及之间的关系 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，我们建议两位专家进行研究 AMN 运动分析实验室评估共济失调的先进测力板测量是否有用 作为这种情况下的评估（目标 2）。最后，我们获得了试点数据，显示关键指标 共济失调、摇摆幅度和步态变量可以使用可穿戴技术进行远程评估。我们建议 评估可穿戴设备是否可用于评估这种情况下的共济失调（目标 3）。 该项目的结果对于促进目前正在研究的疗法的临床研究至关重要 AMN 成人的发育。