title: Plasmatic kinetics of dermatan sulfate during enzyme replacement therapy with iduronate-2-sulfatase in a mucopolysaccharidosis II patient.
abstract: Enzyme replacement therapy (ERT) is the worldwide standard of care for a number of mucopolysaccharidosis (MPS) diseases. We report a kinetic study of plasmatic dermatan sulfate (DS) in a 3-year-old subject affected by a severe form of MPS II during the first 10 months of ERT with Idursulfase. A strong increase in the DS plasmatic concentration was measured immediately after the first enzyme infusion, with a maximum after 3 h, followed by a continuous decrease in the 8-15 days following the beginning of treatment. After this, a constant plasmatic content of DS concentration was observed. Overall, during the 10-month treatment period, ERT reduced the plasmatic concentration of DS up to ~80-85 %, but it was unable to totally remove it from the blood. We can suppose that immediately after the first enzyme administrations, a large amount of abnormal DS is removed from tissues reaching the blood compartment and eliminated via the urine, and thereafter only minimal changes are observed. The persistency of the residual amounts of DS with the actually recommended dosage in our Patient may suggest the opportunity to promote further studies with increased enzyme dosages to completely remove the accumulation of lysosomal DS.
authors.affiliation: Department of Life Sciences, University of Modena & Reggio Emilia, Via Campi 213/D, 41100, Modena, Italy, volpi@unimo.it.
authors.forename: Nicola
authors.initials: N
authors.lastname: Volpi
authors.forename: Lucia
authors.initials: L
authors.lastname: Zampini
authors.forename: Francesca
authors.initials: F
authors.lastname: Maccari
authors.forename: Lucia
authors.initials: L
authors.lastname: Santoro
authors.forename: Fabio
authors.initials: F
authors.lastname: Galeotti
authors.forename: Tiziana
authors.initials: T
authors.lastname: Galeazzi
authors.forename: Orazio
authors.initials: O
authors.lastname: Gabrielli
authors.forename: Giovanni V
authors.initials: GV
authors.lastname: Coppa
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D003871:Dermatan Sulfate / Q000097:blood*; D056947:Enzyme Replacement Therapy; D005260:Female; D006023:Glycoproteins / Q000627:therapeutic use*; D006801:Humans; D007223:Infant; D008297:Male; D016532:Mucopolysaccharidosis II / Q000097:blood* / Q000628:therapy; D055815:Young Adult
chemical_list: D006023:Glycoproteins; C018322:IDS protein, human; D003871:Dermatan Sulfate