Novel candidate disease for gene therapy: metachromatic leukodystrophy.

Metachromatic leukodystrophy (MLD) is a rare, fatal, inherited, autosomal recessive, lysosomal storage disorder, characterized by severe and progressive demyelination affecting the central and peripheral nervous systems. Despite some initial expectations in hematopoietic stem cell transplantation, and despite the ameliorated supportive therapy, MLD remains a life-threatening disease, with an extremely poor quality of life and a severe prognosis for all affected patients. Prospectively, in children affected by MLD, who have no other therapeutic option and an extremely poor prognosis, the potential risks associated with the use of a novel technology, such as gene therapy, might be well balanced by the potential benefit of a positive outcome. Thus, MLD might be considered an optimal candidate disease for testing innovative and potentially efficacious therapeutic approaches. Some of the gene therapy approaches discussed here, such as hematopoietic stem cells gene therapy, are likely to enter clinical testing in the near future.