Oligodendroglial progenitor cell therapy limits central neurological deficits in mice with metachromatic leukodystrophy

Maria I. Givogri, Francesca Galbiati, Stefania Fasano, Stefano Amadio, Laura Perani, Daniela Superchi, Pablo Morana, Ubaldo Del Carro, Sergio Marchesini, Riccardo Brambilla, Lawrence Wrabetz, Ernesto Bongarzone

Research output: Contribution to journalArticlepeer-review


This work describes the first successful oligodendrocyte-based cell therapy for presymptomatic arylsulfatase A (ARSA) null neonate mice, a murine model for human metachromatic leukodystrophy (MLD). We found that oligodendrocyte progenitors (OLPs) engrafted and survived into adulthood when transplanted in the neonatal MLD brain. Transplanted cells integrated nondisruptively, did not produce tumors, and survived as proteolipid protein- and MBP-positive postmitotic myelinating oligodendrocytes (OLs) intermingled with endogenous MLD OLs within the adult MLD white matter. Transplanted MLD mice had reduced sulfatide accumulation in the CNS, increased brain ARSA activity, and full prevention of the electrophysiological and motor deficits that characterize untreated MLD mice. Our results provide direct evidence that healthy OLPs can tolerate the neurotoxic accumulation of sulfatides that evolves during the postnatal development of the MLD brain and contribute to OL cell replacement to limit the accumulation of sulfatides and the evolution of CNS defects in this lysosomal storage disease mouse model.

Original languageEnglish
Pages (from-to)3109-3119
Number of pages11
JournalJournal of Neuroscience
Issue number12
Publication statusPublished - Mar 22 2006


  • Demyelination
  • Leukodystrophy
  • Migration
  • Myelin
  • Oligodendrocytes
  • Transplantation

ASJC Scopus subject areas

  • Neuroscience(all)


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