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Serum MIP‐1 α level: a biomarker for the follow‐up of lentiviral therapy in mucopolysaccharidosis IIIB mice
Author(s) -
Di Natale Paola,
Di Domenico Carmela,
Di Napoli Daniele
Publication year - 2010
Publication title -
journal of inherited metabolic disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 102
eISSN - 1573-2665
pISSN - 0141-8955
DOI - 10.1007/s10545-010-9051-4
Subject(s) - medicine , mucopolysaccharidosis , biomarker , genetic enhancement , cytokine , neurotrophic factors , enzyme replacement therapy , immunology , disease , gene , biology , receptor , biochemistry
Mucopolysaccharidosis (MPS) IIIB is an inherited lysosomal storage disorder caused by deficiency of alpha‐N‐acetylglucosaminidase (NAGLU). The disease is characterized by mild somatic features and severe neurological involvement, with high mortality rates. Although some therapeutic approaches have been applied to the murine model of the disease, no effective therapy is available. Moreover, assessing therapeutic efficacy is challenged by the lack of markers to for progression and severity. In this study, we examined the effect of brain‐directed lentiviral (LV) gene therapy on serum levels of macrophage inflammatory protein 1 alpha (MIP‐1α) and brain‐derived neurotrophic factor (BDNF) proteins in the murine model of MPS IIIB to identify novel serum biomarkers. The cytokine MIP‐1α was elevated in MPS IIIB mouse serum, and following gene therapy, it was reduced to normal levels. For neurotrophin BDNF, the difference in serum levels between MPS IIIB and normal mice was not statistically significant; after LV gene therapy, an increase in protein was found in treated mice, although the values were not statistically significant. Our studies suggest MIP‐1α as the first serum biomarker that could be used to monitor disease progression and treatment for MPS IIIB disease.