Molecular markers for the follow-up of enzyme-replacement therapy in mucopolysaccharidosis type VI disease.
MPS VI (mucopolysaccharidosis type VI) is a lysosomal storage disease in which deficient activity of the enzyme N-acetylgalactosamine 4-sulfatase [ASB (arylsulfatase B)] impairs the stepwise degradation of the GAG (glycosaminoglycan) dermatan sulfate. Clinical studies of ERT (enzyme replacement therapy) by using rhASB (recombinant human ASB) have been reported with promising results. The release of GAG into the urine is currently used as a biomarker of disease, reflecting in some cases disease severity and in all cases therapeutic responsiveness. Using RNA studies in four Italian patients undergoing ERT, we observed that TNFalpha (tumour necrosis factor alpha) might be a biomarker for MPS VI responsive to therapy. In addition to its role as a potential biomarker, TNFalpha expression could provide insights into the possible pathophysiological mechanisms underlying the mucopolysaccharidoses.
Di Natale
Paola
P
Department of Biochemistry and Medical Biotechnologies, University of Naples Federico II, Naples, Italy. dinatale@unina.it
Villani
Guglielmo R D
GR
Parini
Rossella
R
Scarpa
Maurizio
M
Parenti
Giancarlo
G
Pontarelli
Gianfranco
G
Grosso
Michela
M
Sersale
Giovanna
G
Tomanin
Rosella
R
Sibilio
Michelina
M
Barone
Rita
R
Fiumara
Agata
A
D015415:Biomarkers / Q000032:analysis / Q000652:urine; D002648:Child; D002675:Child, Preschool; D015870:Gene Expression / Q000187:drug effects; D006025:Glycosaminoglycans / Q000652:urine; D006801:Humans; D009087:Mucopolysaccharidosis VI / Q000188:drug therapy / Q000235:genetics* / Q000503:physiopathology / Q000652:urine; D009154:Mutation; D020051:N-Acetylgalactosamine-4-Sulfatase / Q000235:genetics / Q000627:therapeutic use*; D012313:RNA / Q000235:genetics; D011994:Recombinant Proteins / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*; D016138:Walking
D015415:Biomarkers; D006025:Glycosaminoglycans; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D012313:RNA; D020051:N-Acetylgalactosamine-4-Sulfatase; C508864:galsulfase