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.
Flavigny
E
E
Inserm U342, Hôpital Saint-Vincent de Paul, Paris, France.
Sanhaj
A
A
Aubourg
P
P
Cartier
N
N
D000326:Adrenoleukodystrophy / Q000235:genetics* / Q000378:metabolism / Q000628:therapy*; D000818:Animals; D002478:Cells, Cultured; D005227:Fatty Acids / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D018014:Gene Transfer Techniques; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D012190:Retroviridae; D014161:Transduction, Genetic
D005227:Fatty Acids