Improved Outcome Assessments in Adrenomyeloneuropathy

改进肾上腺脊髓神经病的结果评估

• 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
• 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

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.

摘要 X连锁肾上腺脑白质营养不良(ALD)，一种由ABCD1突变引起的衰弱神经疾病 基因，是为数不多的可用于新生儿筛查的脑白质营养不良症之一，并由 联邦政府。成人起病的肾上腺髓神经病(AMN)是ALD最常见的表型，AS 有ABCD1致病变化的成年男性和超过一半的女性ALD杂合子会发生 随着时间的推移。尽管儿童起病的脑型ALD的治疗取得了进展，但没有治疗方法 目前可用于AMN。此外，疾病进展缓慢且可变的速度和缺乏 对临床结果评估(COA)的理解阻碍了AMN临床试验的准备。 为了解决这一关键的知识鸿沟，我们建议确定临床结果的新工具。 在AMN中进行评估。我们与ALD Connect(请参阅支持函)合作，这是一个致力于 改善ALD和AMN的护理和治疗。我们共同建立了一个成人AMN评定量表。 基于在项目1中收集的并发数据，这些数据将确定变更的速度和之间的关系 患者报告的结果(PRO)和COA，如步行速度，我们将验证此工具并评估其 用于捕捉疾病进展(目标1)。此外，我们建议由两名专家进行研究 AMN运动分析实验室评估共济失调的先进测力板措施是否有用 作为这种情况下的评估(目标2)。最后，我们获得了试点数据，显示了 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)。 该项目的结果将对促进目前正在进行的治疗的临床研究至关重要。 成人AMN的发展。