Monitoring of therapeutic response using lesion segmentation and DTI in adult cerebral adrenoleukodystrophy treated with Leriglitazone

Motivation: Cerebral adrenoleukodystrophy (CALD) is a rare and devastating demyelinating disease. The standard of care is hematopoeitic stem cell transplantation (HCST), which efficacy is limited to early-stage patients. Goal(s): We studied the efficacy of Leriglitazone in CALD patients, either not eligible or awaiting HSCT. Approach: Leriglitazone was administered to thirteen adult male patients. They underwent brain MRI every 3 months, with a quantitative analysis of lesion volumes on FLAIR, diffusion tensor parameters and gadolinium enhancements. Results: The disease stabilized in all patients awaiting HSCT. Corticospinal tract lesions downsized in most patients and turned gadolinium-negative, showing a selective effect of this molecule on motor pathways. Impact: Cerebral adrenoleukodystrophy is a devastating demyelinating disease, fatal for all patients without early stem cell transplantation. We showed that Leriglitazone represents a therapeutic alternative, allowing clinical and radiological stabilization in ten men. Remarkably, motor pathways lesions downsized and turned gadolinium-negative.