title: Enhanced brain distribution of modified aspartoacylase.
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.
authors: Department of Chemistry and Biochemistry, University of Toledo, Toledo, OH 43606, USA.
authors: Nitesh K
authors: NK
authors: Poddar
authors: Department of Chemistry and Biochemistry, University of Toledo, Toledo, OH 43606, USA.
authors: Stephen
authors: S
authors: Zano
authors: Department of Neurosciences, University of Toledo, Toledo, OH 43614, USA.
authors: Reka
authors: R
authors: Natarajan
authors: Department of Neurosciences, University of Toledo, Toledo, OH 43614, USA.
authors: Bryan
authors: B
authors: Yamamoto
authors: Department of Chemistry and Biochemistry, University of Toledo, Toledo, OH 43606, USA. Electronic address: ron.viola@utoledo.edu.
authors: Ronald E
authors: RE
authors: Viola
mesh_terms: D000581:Amidohydrolases / Q000276:immunology / Q000493:pharmacokinetics*; D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D017825:Canavan Disease / Q000188:drug therapy; D004353:Drug Evaluation, Preclinical; D056947:Enzyme Replacement Therapy; D006801:Humans; D008297:Male; D011092:Polyethylene Glycols / Q000493:pharmacokinetics*; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
chemical_list: D011092:Polyethylene Glycols; D000581:Amidohydrolases; C019751:aspartoacylase
keywords: Aspartoacylase; Blood–brain barrier; Canavan disease; Enzyme replacement therapy; PEGylation