Efficacy of a combined intracerebral and systemic gene delivery approach for the treatment of a severe lysosomal storage disorder

Carmine Spampanato, Elvira De Leonibus, Paola Dama, Annagiusi Gargiulo, Alessandro Fraldi, Nicolina Cristina Sorrentino, Fabio Russo, Edoardo Nusco, Alberto Auricchio, Enrico M. Surace, Andrea Ballabio

Research output: Contribution to journalArticlepeer-review


Multiple sulfatase deficiency (MSD), a severe autosomal recessive disease is caused by mutations in the sulfatase modifying factor 1 gene (Sumf1). We have previously shown that in the Sumf1 knockout mouse model (Sumf1 /) sulfatase activities are completely absent and, similarly to MSD patients, this mouse model displays growth retardation and early mortality. The severity of the phenotype makes MSD unsuitable to be treated by enzyme replacement or bone marrow transplantation, hence the importance of testing the efficacy of novel treatment strategies. Here we show that recombinant adeno-associated virus serotype 9 (rAAV9) vector injected into the cerebral ventricles of neonatal mice resulted in efficient and widespread transduction of the brain parenchyma. In addition, we compared a combined, intracerebral ventricles and systemic, administration of an rAAV9 vector encoding SUMF1 gene to the single administrationseither directly in brain, or systemic alone in MSD mice. The combined treatment resulted in the global activation of sulfatases, near-complete clearance of glycosaminoglycans (GAGs) and decrease of inflammation in both the central nervous system (CNS) and visceral organs. Furthermore, behavioral abilities were improved by the combined treatment. These results underscore that the combined mode of rAAV9 vector administration is an efficient option for the treatment of severe whole-body disorders.

Original languageEnglish
Pages (from-to)860-869
Number of pages10
JournalMolecular Therapy
Issue number5
Publication statusPublished - May 2011

ASJC Scopus subject areas

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


Dive into the research topics of 'Efficacy of a combined intracerebral and systemic gene delivery approach for the treatment of a severe lysosomal storage disorder'. Together they form a unique fingerprint.

Cite this