Long-term amelioration of feline mucopolysaccharidosis VI after AAV-mediated liver gene transfer

Gabriella Cotugno, Patrizia Annunziata, Alessandra Tessitore, Thomas O'Malley, Anita Capalbo, Armida Faella, Rosa Bartolomeo, Patricia O'Donnell, Ping Wang, Fabio Russo, Meg M. Sleeper, Van W. Knox, Steven Fernandez, Leah Levanduski, John Hopwood, Elvira De Leonibus, Mark Haskins, Alberto Auricchio

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60 Citations (Scopus)


Mucopolysaccharidosis VI (MPS VI) is caused by deficient arylsulfatase B (ARSB) activity resulting in lysosomal storage of glycosaminoglycans (GAGs). MPS VI is characterized by dysostosis multiplex, organomegaly, corneal clouding, and heart valve thickening. Gene transfer to a factory organ like liver may provide a lifetime source of secreted ARSB. We show that intravascular administration of adeno-associated viral vectors (AAV) 2/8-TBG-felineARSB in MPS VI cats resulted in ARSB expression up to 1 year, the last time point of the study. In newborn cats, normal circulating ARSB activity was achieved following delivery of high vector doses (6 × 1013 genome copies (gc)/kg) whereas delivery of AAV2/8 vector doses as low as 2 × 1012 gc/kg resulted in higher than normal serum ARSB levels in juvenile MPS VI cats. In MPS VI cats showing high serum ARSB levels, independent of the age at treatment, we observed: (i) clearance of GAG storage, (ii) improvement of long bone length, (iii) reduction of heart valve thickness, and (iv) improvement in spontaneous mobility. Thus, AAV2/ 8-mediated liver gene transfer represents a promising therapeutic strategy for MPS VI patients.

Original languageEnglish
Pages (from-to)461-469
Number of pages9
JournalMolecular Therapy
Issue number3
Publication statusPublished or Issued - Mar 2011

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Pharmacology
  • Drug Discovery

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