The promising results of a gene therapy clinical trial for metachromatic leukodystrophy (MLD), an inherited lysosomal storage disease caused by arylsulfatase A (ARSA) deficiency, have bee recently published in Science. Three MLD patients in a presymptomatic stage were infused with hematopoietic stem cells genetically corrected with lentiviral vectors and showed extensive and stable ARSA gene replacement, which led to high enzyme expression throughout hematopoietic lineages and in the cerebrospinal fluid. Importantly, the disease did not manifest or progress in the three patients 7 to 21 months beyond the predicted age of symptom onset. Analyses of vector integrations revealed no evidence of aberrant clonal behavior that has been a significant issue for other integrating vectors (e.g. retrovirus).
Posted by Nicola Brunetti-Pierri, MD