Improved Outcome Assessments in Adrenomyeloneuropathy

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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.