Metachromatic leukodystrophy (MLD) is a rare, progressive lysosomal storage disease caused by mutations in the gene encoding arylsulfatase A (ARSA), causing disease in the central and peripheral nervous systems. MLD presents in toddlers (late infantile disease) or in children (juvenile disease) with gait disturbances, loss of developmental milestones, and cognitive decline, leading to death in childhood. It is frequently not diagnosed until the later symptomatic phase when it is too late to intervene. Haematopoietic stem-cell transplantation (HSCT) from allogeneic donors has been used with mixed results. Although HSCT can slow progression of disease in the central nervous system, it does not prevent progression in the peripheral nervous system. HSCT is also associated with risks of graft-versus-host disease and treatment-related toxicity. Additionally, small trials of intrathecal gene therapy in mice or humans did not result in improvement in symptoms of clinical disease. Thus, new therapeutic approaches are desperately needed.
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