To report the ability of calibrated MR diffusion biomarkers to assess progression and regression of microstructural alterations in adrenomyeloneuropathy (AMN) in response to leriglitazone.

AMN is the most common peroxisomal disorder caused by ABCD1 pathogenic variants on the X-chromosome, resulting in accumulation of very-long chain fatty acids in plasma and in tissues including brain white matter. Brain diffusion MRI biomarkers are sensitive outcome measures to follow disease progression in AMN but their application for clinical use in multicenter frameworks is very limited. Calibration methods to reduce inter-site variability as well as the use of standardized indices are proposed to efficiently monitor myelin alterations.

Braintale MRI sub-study is a bi-centric part of ADVANCE study, a randomized, double-blind, placebo-controlled, multicenter study with open-label treatment extension. Recruitment of participants was carried out at the Pitié-Salpêtrière Hospital, Paris, France and at the Academic Medical Center, Amsterdam, Netherlands. Forty male patients (21 in Paris, 19 in Amsterdam) with AMN were randomly assigned to the treatment/active group (n = 27) and the placebo group (n = 13). Thirty age-matched healthy volunteers were included for diffusion MRI calibration purpose. MRI scans were measured at baseline and year-2. The BQ-RD-index19-change evaluating the significant positive or negative changes in regional radial diffusivity MRI biomarkers were compared in active and placebo groups.

BQ-RD-index19-changes (p<0.007) were significantly lower in the active group (=-1 in average) compared to placebo (=+1), indicating that the number of regions that improved in radial diffusivity, a marker of myelin integrity, compared to those that deteriorated was higher in active patients than in the placebo group.

Diffusion MRI marker BQ-RD-index19 showed decreased disease progression in response to leriglitazone in a subgroup of the ADVANCE study. This marker may enable efficient monitoring of disease progression and response to treatment in patients with AMN in a clinical setting.