Alterations of Plasmatic Biomarkers of Neurodegeneration in Mucopolysaccharidosis Type II Patients Under Enzyme Replacement Therapy

Mucopolysaccharidosis type II (MPS II) is a disorder caused by a deficient activity of iduronate-2-sulfatase, a lysosomal enzyme responsible for degrading glycosaminoglycans (GAGs). The abnormal storage of GAGs within lysosomes disrupts cellular homeostasis and leads to a severe symptomatology. Pati...

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Published in:Cell biochemistry and biophysics 2023-09, Vol.81 (3), p.533-542
Main Authors: Jacques, Carlos Eduardo Diaz, Guerreiro, Gilian, Lopes, Franciele Fatima, de Souza, Carolina F. Moura, Giugliani, Roberto, Vargas, Carmen Regla
Format: Article
Language:English
Subjects:
Biochemistry
Biological and Medical Physics
Biomarkers
Biomedical and Life Sciences
Biophysics
Biotechnology
Body weight
Brain-derived neurotrophic factor
Cell adhesion
Cell adhesion molecules
Cell Biology
Cognition
Enzymes
Genetic disorders
Glycosaminoglycans
Growth factors
Homeostasis
Intellectual disabilities
Life Sciences
Lysosomes
Medical imaging
Metabolic disorders
Mucopolysaccharidosis
Neural cell adhesion molecule
Neurodegeneration
Neuroimaging
Original Paper
Pharmacology/Toxicology
Platelet-derived growth factor
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Summary:Mucopolysaccharidosis type II (MPS II) is a disorder caused by a deficient activity of iduronate-2-sulfatase, a lysosomal enzyme responsible for degrading glycosaminoglycans (GAGs). The abnormal storage of GAGs within lysosomes disrupts cellular homeostasis and leads to a severe symptomatology. Patients present neuropsychiatric impairment characterized by mental retardation and impaired cognition. The aim of this study was to quantify four neurodegeneration biomarkers in plasma: brain-derived neurotrophic factor (BDNF), platelet-derived growth factor (PDGF-AA), neural cell adhesion molecule (NCAM) and cathepsin-D, as well as to identify possible correlations with urinary GAGs in seven patients undergoing treatment with ERT (Elaprase® 0.5 mg/kg of body weight). Patients with both severe and attenuated forms of MPS II showed signs of neurodegeneration in neuroimaging exams. Patients have a decrease in BDNF and PDGF-AA concentrations, and an increase in NCAM level compared to controls. No alterations in cathepsin-D concentration were seen. GAGs levels were higher in patients than in controls, but no significant correlations between GAGs and biomarkers were observed. These results evidence that patients have neurodegeneration and that monitoring these biomarkers might be useful for assessing this process. To this date, this is the first work to analyze these plasmatic markers of neurodegeneration in patients.
ISSN:1085-9195
1559-0283
DOI:10.1007/s12013-023-01149-w