Gene therapy for leukodystrophies

Leukodystrophies (LDs) refer to a group on inherited diseases in which molecular abnormalities of glial cells are responsible for exclusive or predominant defects in myelin formation and/or maintenance within the central and, sometimes, the peripheral nervous system. For three of them [X-linked adrenoleukodystrophy (X-ALD), metachromatic (MLD) and globoid cell LDs], a gene therapy strategy aiming at transferring the disease gene into autologous hematopoietic stem cells (HSCs) using lentiviral vectors has been developed and has already entered into the clinics for X-ALD and MLD. Long-term follow-up has shown that HSCs gene therapy can arrest the devastating progression of X-ALD. Brain gene therapy relying upon intracerebral injections of adeno-associated vectors is also envisaged for MLD. The development of new gene therapy viral vectors allowing targeting of the disease gene into oligodendrocytes or astrocytes should soon benefit other forms of LDs. © The Author 2011. Published by Oxford University Press. All rights reserved.