Enhanced brain distribution of modified aspartoacylase

Nitesh K. Poddar, Stephen Zano, Reka Natarajan, Bryan Yamamoto, Ronald E. Viola

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Canavan disease is a fatal neurological disorder caused by defects in the gene that produces the enzyme aspartoacylase. Enzyme replacement therapy can potentially be used to overcome these defects if a stable enzyme form that can gain access to the appropriate neural cells can be produced. Achieving the proper cellular targeting requires a modified form of aspartoacylase that can traverse the blood-brain barrier. A PEGylated form of aspartoacylase that shows dramatic enhancement in brain tissue access and distribution has been produced. While the mechanism of transport has not yet been established, this modified enzyme is significantly less immunogenic than unmodified aspartoacylase. These improved properties set the stage for more extensive enzyme replacement trials as a possible treatment strategy.

Original languageEnglish (US)
Pages (from-to)219-224
Number of pages6
JournalMolecular Genetics and Metabolism
Volume113
Issue number3
DOIs
StatePublished - Nov 1 2014
Externally publishedYes

Fingerprint

Brain
Enzymes
Canavan Disease
Enzyme Replacement Therapy
Tissue Distribution
Nervous System Diseases
Blood-Brain Barrier
Defects
Genes
aspartoacylase
Tissue
Therapeutics

Keywords

  • Aspartoacylase
  • Blood-brain barrier
  • Canavan disease
  • Enzyme replacement therapy
  • PEGylation

ASJC Scopus subject areas

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

Cite this

Enhanced brain distribution of modified aspartoacylase. / Poddar, Nitesh K.; Zano, Stephen; Natarajan, Reka; Yamamoto, Bryan; Viola, Ronald E.

In: Molecular Genetics and Metabolism, Vol. 113, No. 3, 01.11.2014, p. 219-224.

Research output: Contribution to journalArticle

Poddar, Nitesh K. ; Zano, Stephen ; Natarajan, Reka ; Yamamoto, Bryan ; Viola, Ronald E. / Enhanced brain distribution of modified aspartoacylase. In: Molecular Genetics and Metabolism. 2014 ; Vol. 113, No. 3. pp. 219-224.
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