Different serum enzyme levels are required to rescue the various systemic features of the mucopolysaccharidoses

Gabriella Cotugno, Alessandra Tessitore, Anita Capalbo, Patrizia Annunziata, Caterina Strisciuglio, Armida Faella, Michela Aurilio, Maurizio Di Tommaso, Fabio Russo, Antonio Mancini, Elvira De Leonibus, Luigi Aloj, Alberto Auricchio

Research output: Contribution to journalArticlepeer-review

Abstract

Mucopolysaccharidoses (MPSs) are lysosomal storage disorders characterized by progressive accumulation of glycosaminoglycans (GAGs) in various tissues. Enzyme replacement therapy (ERT) for several MPSs is available to date. However, the efficacy of ERT is limited, in particular in compartments such as bone, cartilage, the brain, and the eyes. We selected a rodent model of an MPS, with no central nervous system storage, to study the impact, on systemic features of the disease, of various stable levels of exogenous enzymes produced by adeno-associated viral vector (AAV)-mediated liver gene transfer. Low levels (6% of normal) of circulating enzyme were enough to reduce storage and inflammation in the visceral organs and to ameliorate skull abnormalities; intermediate levels (11% of normal) were required to reduce urinary GAG excretion; and high levels (≥50% of normal) rescued abnormalities of the long bones and motor activity. These data will be instrumental to design appropriate clinical protocols based on either enzyme or gene replacement therapy for MPS and to predict their impact on the pathological features of MPS.

Original languageEnglish
Pages (from-to)555-569
Number of pages15
JournalHuman Gene Therapy
Volume21
Issue number5
DOIs
Publication statusPublished - May 1 2010

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

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