Modification of aspartoacylase for potential use in enzyme replacement therapy for the treatment of Canavan disease

Stephen Zano, Radhika Malik, Sylvia Szucs, Reuben Matalon, Ronald E. Viola

Research output: Contribution to journalArticlepeer-review

17 Scopus citations


Canavan disease is a fatal neurological disease without any effective treatments to slow the relentless progress of this disorder. Enzyme replacement therapy has been used effectively to treat a number of metabolic disorders, but the presence of the blood-brain-barrier presents an additional challenge in the treatment of neurological disorders. Studies have begun with the aim of establishing a treatment protocol that can effectively replace the defective enzyme in Canavan disease patients. The human enzyme, aspartoacylase, has been cloned, expressed and purified, and the surface lysyl groups modified through PEGylation. Fully active modified enzymes were administered to mice that are defective in this enzyme and that show many of the symptoms of Canavan disease. Statistically significant increases in brain enzyme activity levels have been achieved in this animal model, as well as decreases in the elevated substrate levels that mimic those found in Canavan disease patients. These results demonstrate that the modified enzyme is gaining access to the brain and functions to correct this metabolic defect. The stage is now set for a long term study to optimize this enzyme replacement approach for the development of a treatment protocol.

Original languageEnglish (US)
Pages (from-to)176-180
Number of pages5
JournalMolecular Genetics and Metabolism
Issue number2
StatePublished - Feb 2011


  • Animal model
  • Aspartoacylase
  • Canavan disease
  • Enzyme replacement therapy
  • PEGylation

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Endocrinology


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