Therapeutic Potential and Safety of Intravenous ARSA-Overexpressing Mesenchymal Stem Cells in a Porcine Study of Metachromatic Leukodystrophy

Metachromatic leukodystrophy (MLD) results from arylsulfatase A (ARSA) deficiency and progressive demyelination. This study evaluates the safety and therapeutic potential of intravenously administered allogeneic mesenchymal stem cells transduced with AAV9 encoding human ARSA in a porcine in vivo study. While ARSA activity in plasma and cerebrospinal fluid did not significantly change, CNS tissues showed a marked increase in ARSA activity, indicating successful CNS targeting and local enzyme expression. Biochemical parameters and cytokine profiles remained within physiological ranges, demonstrating good tolerability and absence of systemic inflammation. These findings suggest that MSC-based delivery of AAV9-ARSA is a safe approach capable of enhancing ARSA activity in the CNS and may represent a promising therapeutic strategy for MLD.