Disease Fact Sheet: Pediatric Leukodystrophies (LDs)
Clinical Status: Currently, most patients with LDs can only be offered supportive treatment; few disease-modifying or curative strategies are available. Metabolic LDs due to enzymatic dysfunction, including the lysosomal storage diseases such as globoid cell leukodystrophy, and peroxisomal disorders like drenoleukodystrophy, may be offered HSCT/USCT. However, the benefits of this approach are limited to mild and early-diagnosed cases; this approach cannot restore cells already lost, or repair damage that has already occurred. For that purpose, cell replacement therapy with human neural or glial progenitor cells is under development. This approach was first trialed in a phase I safety study in patients with Pelizaeus-Merzbacher disease, a congenital leukodystrophy characterized by mutations in the gene coding proteolipid protein (PLP), which is required for myelination. This study provided the first proof of principle that human NPCs transplanted into the cerebral white matter are well tolerated and could engraft the white matter of affected children. Yet the use of fetal tissue-derived cells hindered the further development of this strategy. As a result, more recent efforts have focused on the use of glial progenitor cells derived from human pluripotent stem cells.