Retroviral-mediated adrenoleukodystrophy-related gene transfer corrects very long chain fatty acid metabolism in adrenoleukodystrophy fibroblasts: implications for therapy.

X-linked adrenoleukodystrophy is a demyelinating disorder of the central nervous system with an impaired very long chain fatty acid metabolism. The adrenoleukodystrophy gene encodes a peroxisomal membrane protein that is part of a family of related ATP-binding transporters including the adrenoleukodystrophy-related protein. The adrenoleukodystrophy protein and adrenoleukodystrophy-related protein show 66% identity and have a mirror expression in most mouse tissues. We show that retroviral-mediated adrenoleukodystrophy-related gene transfer corrects very long chain fatty acid accumulation in adrenoleukodystrophy fibroblasts, irrespective of the presence or absence of adrenoleukodystrophy protein. Pharmacological approaches aiming at overexpressing the adrenoleukodystrophy-related gene in the central nervous system of adrenoleukodystrophy patients might thus offer new therapeutic leads.