Identification of adrenoleukodystrophy gene and future therapy

ABSTRACT Adrenoleukodystrophy (ALD) is an X-linked disease characterized by progressive demyelination of the central nervous system (CMS) and adrenal insufficiency. Adrenal insufficiency may

occur in boys with ALD who have not yet developed neurological symptoms and even remain the only clinical manifestation ot ALD. However, when the neurologic manifestations associated with

demyelination starts, no children escape rapid and severe deterioration leading to death within 2-4 years. The normal oxidation of very long chain fatty (VLCFA)-CoA in ALD patien's

fibroblasts suggested that the gene coding for VLCFA-CoA synthetase was a candidate gene for ALD. Using positional cloning, we identified in Xq28 a gene partially deleted in 7% of ALD

patients. Candidate exons were used to isolate cDNAs by exon-connection. The predicted protein sequence (745 aa) encode a peroxisomal transporter that may be involved in the import of the

VLCFA-CoA synthetase but not the enzyme itself. We have moreover demonstrated that bone-marrow transplantation can correct or stabilize the evolution of the disease in 3 patients with the

severe cerebral form. The use of autologous bone marrow after the insertion of a normal gene would circumvent the need for a histocompatible donnor and may provide the most suitable gene

therapy approach before attempting to deliver the ALD in the cells of CNS where it is expressed. ARTICLE PDF AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Inserm U342 and Pediatric

Endocrinology, Hôpital Saint Vincent de Paul, Paris, FR P Aubourg, J Mosser, A M Douar, C Sarde, J L Chaussain & J L Mandel * Inserm U184, Strasbourg, FR P Aubourg, J Mosser, A M Douar, 

C Sarde, J L Chaussain & J L Mandel Authors * P Aubourg View author publications You can also search for this author inPubMed Google Scholar * J Mosser View author publications You can

also search for this author inPubMed Google Scholar * A M Douar View author publications You can also search for this author inPubMed Google Scholar * C Sarde View author publications You

can also search for this author inPubMed Google Scholar * J L Chaussain View author publications You can also search for this author inPubMed Google Scholar * J L Mandel View author

publications You can also search for this author inPubMed Google Scholar RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Aubourg, P., Mosser, J., Douar,

A. _et al._ Identification of adrenoleukodystrophy gene and future therapy. _Pediatr Res_ 33 (Suppl 5), S15 (1993). https://doi.org/10.1203/00006450-199305001-00073 Download citation * Issue

Date: 01 May 1993 * DOI: https://doi.org/10.1203/00006450-199305001-00073 SHARE THIS ARTICLE Anyone you share the following link with will be able to read this content: Get shareable link

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