Improved Outcome Assessments in Adrenomyeloneuropathy

摘要 X连锁肾上腺脑白质营养不良（ALD），一种由ABCD 1突变引起的衰弱性神经系统疾病 基因，是为数不多的脑白质营养不良，新生儿筛查是可用的，并建议由 联邦政府。成人型肾上腺脊髓神经病（AMN）是ALD最常见的表型， ABCD 1发生致病性变化的成年男性和超过一半的女性ALD杂合子发生 随着时间的推移。尽管儿童期脑型ALD的治疗取得了进展，但没有治疗方法。 目前，AMN。此外，缓慢和可变的疾病进展速度和缺乏 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差距，我们建议确定新的工具，临床结果 在AMN中进行评估。我们与ALD Connect（见支持信）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评级量表。 根据项目1中收集的同时数据，这些数据将确定变化率和 患者报告的结局（PRO）和COA（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，我们建议在两个专家小组进行研究， AMN运动分析实验室评估共济失调的高级测力板测量是否有用 在这种情况下的评估（目标2）。最后，我们获得的试点数据显示， 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。我们提出 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进行的治疗的临床研究至关重要。 成人AMN的发展。

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.