Stem cell-transplantation therapy for adrenoleukodystrophy: current perspectives

Weston Miller

Department of Pediatrics, Division of Blood and Marrow Transplantation, University of Minnesota, Minneapolis, MN, USA

Abstract: Adrenoleukodystrophy (ALD) is a rare, X-linked peroxisomal disorder of impaired very long-chain fatty-acid metabolism. It results from various mutations in the ABCD1 gene (Xq28). All males with the biochemical defect of ALD are at risk of developing cerebral white-matter disease (cALD) during their lifetime. Thirty-five percent of ALD patients develop cALD in boyhood, a life-threatening phenotype characterized by rapidly expanding, neuroinflammatory demyelination and irreversible clinical neurologic decline. The ABCD1 genotype does not predict susceptibility to or protection from the childhood cALD phenotype; therefore, clinicians must remain ever vigilant for its development when monitoring ALD patients. Currently, allogeneic hematopoietic cell transplantation (HCT) is the standard of care for boyhood cALD. While HCT provides dramatic functional survival benefit in boys with early, presymptomatic cALD, outcomes are less favorable and less predictable for those with more advanced disease. Furthermore, little is known about how successful HCT in childhood might impact the onset of central nervous system disease in adulthood. Finally, investigations of experimental gene-therapy strategies are ongoing. This review explores current perspectives of stem cell transplantation in cALD.

Keywords: adrenoleukodystrophy, cerebral adrenoleukodystrophy, stem cell transplantation, bone marrow transplantation, umbilical cord-blood transplantation, hematopoietic cell transplantation