MACROPHAGES ACTIVATION PATTERN IN X LINKED ADRENOLEUKODYSTROPHY – MATTRIX

X-linked adrenoleukodystrophy (X-ALD) shows a phenotypic variability, ranging from the devastating inflammatory childhood cerebral ALD to a progressive spastic paraplegia in adulthood. Lipid compounds, which are abnormal in X-ALD, play a critical role in the differentiation states of macrophages, cells implicated in disease pathogenesis. We will explore how X-ALD mutations perturb differently immune cells comparing patients with different disease forms. We plan to reconstitute how macrophages handle specific stimuli (acquiring degenerative versus regenerative phenotype) and see how X-ALD mutations affect their responsiveness. Understanding the inter-individual heterogeneity of macrophages responsiveness will help us identify novel biomarkers linked to disease severity. We also plan to determine molecular pathway(s) that can be corrected to gear macrophages toward a pro-regenerative phenotype. If successful, our approach may lead to “individualized medicine” for these patients.