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Alpha-N-Acetylglucosaminidase

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Paola Di Natale – 1st expert on this subject based on the ideXlab platform

  • Intracranial gene delivery of LV-NAGLU vector corrects neuropathology in murine MPS IIIB.
    American journal of medical genetics. Part A, 2020
    Co-Authors: Carmela Di Domenico, Daniele Di Napoli, Guglielmo R D Villani, Edoardo Nusco, Gaetano Calì, Lucio Nitsch, Paola Di Natale

    Abstract:

    Mucopolysacccharidosis (MPS) IIIB is an inherited lysosomal storage disorder caused by the deficiency of Alpha-N-Acetylglucosaminidase (NAGLU). The disease is characterized by mild somatic features and severe neurological involvement with high mortality. Although several therapeutic approaches have been applied to the murine model of the disease, no effective therapy is available for patients. In this study, we used the lentiviral-NAGLU vector to deliver the functional human NAGLU gene into the brain of young adult MPS IIIB mice. We report the restoration of active enzyme with a sustained expression throughout a large portion of the brain, and a significantly improved behavioral performance of treated animals. Moreover, we analyzed the effect of therapy on the expression profile of some genes related to neurotrophic signaling molecules and inflammatory cytokines previously found altered in MPS IIIB mice. At 1 month from treatment, the level of cerebellin 1 (Cbln1) was decreased while the brain-derived neurotrophic factor (Bdnf) expression was increased, both reaching normal values. At 6 months from treatment a significant reduction in the expression of all the inflammation- and oxidative stress-related genes was observed, as well as the maintenance of the correction of the Bdnf gene expression. These results indicate that NAGLU delivery from intracerebral sources has the capacity to alleviate most disease manifestations in MPS IIIB mice; furthermore, Bdnf might be a response-to-therapy biomarker for MPS IIIB.

  • Serum MIP-1 α level: a biomarker for the follow-up of lentiviral therapy in mucopolysaccharidosis IIIB mice
    Journal of Inherited Metabolic Disease, 2010
    Co-Authors: Paola Di Natale, Carmela Di Domenico, Daniele Di Napoli

    Abstract:

    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.

  • Intracranial gene delivery of LV-NAGLU vector corrects neuropathology in murine MPS IIIB.
    American Journal of Medical Genetics Part A, 2009
    Co-Authors: Carmela Di Domenico, Daniele Di Napoli, Guglielmo R D Villani, Edoardo Nusco, Gaetano Calì, Lucio Nitsch, Paola Di Natale

    Abstract:

    Mucopolysacccharidosis (MPS) IIIB is an inherited lysosomal storage disorder caused by the deficiency of Alpha-N-Acetylglucosaminidase (NAGLU). The disease is characterized by mild somatic features and severe neurological involvement with high mortality. Although several therapeutic approaches have been applied to the murine model of the disease, no effective therapy is available for patients. In this study, we used the lentiviral-NAGLU vector to deliver the functional human NAGLU gene into the brain of young adult MPS IIIB mice. We report the restoration of active enzyme with a sustained expression throughout a large portion of the brain, and a significantly improved behavioral performance of treated animals. Moreover, we analyzed the effect of therapy on the expression profile of some genes related to neurotrophic signaling molecules and inflammatory cytokines previously found altered in MPS IIIB mice. At 1 month from treatment, the level of cerebellin 1 (Cbln1) was decreased while the brain-derived neurotrophic factor (Bdnf) expression was increased, both reaching normal values. At 6 months from treatment a significant reduction in the expression of all the inflammation- and oxidative stress-related genes was observed, as well as the maintenance of the correction of the Bdnf gene expression. These results indicate that NAGLU delivery from intracerebral sources has the capacity to alleviate most disease manifestations in MPS IIIB mice; furthermore, Bdnf might be a response-to-therapy biomarker for MPS IIIB. © 2009 Wiley-Liss, Inc.

Carmela Di Domenico – 2nd expert on this subject based on the ideXlab platform

  • Intracranial gene delivery of LV-NAGLU vector corrects neuropathology in murine MPS IIIB.
    American journal of medical genetics. Part A, 2020
    Co-Authors: Carmela Di Domenico, Daniele Di Napoli, Guglielmo R D Villani, Edoardo Nusco, Gaetano Calì, Lucio Nitsch, Paola Di Natale

    Abstract:

    Mucopolysacccharidosis (MPS) IIIB is an inherited lysosomal storage disorder caused by the deficiency of Alpha-N-Acetylglucosaminidase (NAGLU). The disease is characterized by mild somatic features and severe neurological involvement with high mortality. Although several therapeutic approaches have been applied to the murine model of the disease, no effective therapy is available for patients. In this study, we used the lentiviral-NAGLU vector to deliver the functional human NAGLU gene into the brain of young adult MPS IIIB mice. We report the restoration of active enzyme with a sustained expression throughout a large portion of the brain, and a significantly improved behavioral performance of treated animals. Moreover, we analyzed the effect of therapy on the expression profile of some genes related to neurotrophic signaling molecules and inflammatory cytokines previously found altered in MPS IIIB mice. At 1 month from treatment, the level of cerebellin 1 (Cbln1) was decreased while the brain-derived neurotrophic factor (Bdnf) expression was increased, both reaching normal values. At 6 months from treatment a significant reduction in the expression of all the inflammation- and oxidative stress-related genes was observed, as well as the maintenance of the correction of the Bdnf gene expression. These results indicate that NAGLU delivery from intracerebral sources has the capacity to alleviate most disease manifestations in MPS IIIB mice; furthermore, Bdnf might be a response-to-therapy biomarker for MPS IIIB.

  • Serum MIP-1 α level: a biomarker for the follow-up of lentiviral therapy in mucopolysaccharidosis IIIB mice
    Journal of Inherited Metabolic Disease, 2010
    Co-Authors: Paola Di Natale, Carmela Di Domenico, Daniele Di Napoli

    Abstract:

    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.

  • Intracranial gene delivery of LV-NAGLU vector corrects neuropathology in murine MPS IIIB.
    American Journal of Medical Genetics Part A, 2009
    Co-Authors: Carmela Di Domenico, Daniele Di Napoli, Guglielmo R D Villani, Edoardo Nusco, Gaetano Calì, Lucio Nitsch, Paola Di Natale

    Abstract:

    Mucopolysacccharidosis (MPS) IIIB is an inherited lysosomal storage disorder caused by the deficiency of Alpha-N-Acetylglucosaminidase (NAGLU). The disease is characterized by mild somatic features and severe neurological involvement with high mortality. Although several therapeutic approaches have been applied to the murine model of the disease, no effective therapy is available for patients. In this study, we used the lentiviral-NAGLU vector to deliver the functional human NAGLU gene into the brain of young adult MPS IIIB mice. We report the restoration of active enzyme with a sustained expression throughout a large portion of the brain, and a significantly improved behavioral performance of treated animals. Moreover, we analyzed the effect of therapy on the expression profile of some genes related to neurotrophic signaling molecules and inflammatory cytokines previously found altered in MPS IIIB mice. At 1 month from treatment, the level of cerebellin 1 (Cbln1) was decreased while the brain-derived neurotrophic factor (Bdnf) expression was increased, both reaching normal values. At 6 months from treatment a significant reduction in the expression of all the inflammation- and oxidative stress-related genes was observed, as well as the maintenance of the correction of the Bdnf gene expression. These results indicate that NAGLU delivery from intracerebral sources has the capacity to alleviate most disease manifestations in MPS IIIB mice; furthermore, Bdnf might be a response-to-therapy biomarker for MPS IIIB. © 2009 Wiley-Liss, Inc.

Daniele Di Napoli – 3rd expert on this subject based on the ideXlab platform

  • Intracranial gene delivery of LV-NAGLU vector corrects neuropathology in murine MPS IIIB.
    American journal of medical genetics. Part A, 2020
    Co-Authors: Carmela Di Domenico, Daniele Di Napoli, Guglielmo R D Villani, Edoardo Nusco, Gaetano Calì, Lucio Nitsch, Paola Di Natale

    Abstract:

    Mucopolysacccharidosis (MPS) IIIB is an inherited lysosomal storage disorder caused by the deficiency of Alpha-N-Acetylglucosaminidase (NAGLU). The disease is characterized by mild somatic features and severe neurological involvement with high mortality. Although several therapeutic approaches have been applied to the murine model of the disease, no effective therapy is available for patients. In this study, we used the lentiviral-NAGLU vector to deliver the functional human NAGLU gene into the brain of young adult MPS IIIB mice. We report the restoration of active enzyme with a sustained expression throughout a large portion of the brain, and a significantly improved behavioral performance of treated animals. Moreover, we analyzed the effect of therapy on the expression profile of some genes related to neurotrophic signaling molecules and inflammatory cytokines previously found altered in MPS IIIB mice. At 1 month from treatment, the level of cerebellin 1 (Cbln1) was decreased while the brain-derived neurotrophic factor (Bdnf) expression was increased, both reaching normal values. At 6 months from treatment a significant reduction in the expression of all the inflammation- and oxidative stress-related genes was observed, as well as the maintenance of the correction of the Bdnf gene expression. These results indicate that NAGLU delivery from intracerebral sources has the capacity to alleviate most disease manifestations in MPS IIIB mice; furthermore, Bdnf might be a response-to-therapy biomarker for MPS IIIB.

  • Serum MIP-1 α level: a biomarker for the follow-up of lentiviral therapy in mucopolysaccharidosis IIIB mice
    Journal of Inherited Metabolic Disease, 2010
    Co-Authors: Paola Di Natale, Carmela Di Domenico, Daniele Di Napoli

    Abstract:

    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.

  • Intracranial gene delivery of LV-NAGLU vector corrects neuropathology in murine MPS IIIB.
    American Journal of Medical Genetics Part A, 2009
    Co-Authors: Carmela Di Domenico, Daniele Di Napoli, Guglielmo R D Villani, Edoardo Nusco, Gaetano Calì, Lucio Nitsch, Paola Di Natale

    Abstract:

    Mucopolysacccharidosis (MPS) IIIB is an inherited lysosomal storage disorder caused by the deficiency of Alpha-N-Acetylglucosaminidase (NAGLU). The disease is characterized by mild somatic features and severe neurological involvement with high mortality. Although several therapeutic approaches have been applied to the murine model of the disease, no effective therapy is available for patients. In this study, we used the lentiviral-NAGLU vector to deliver the functional human NAGLU gene into the brain of young adult MPS IIIB mice. We report the restoration of active enzyme with a sustained expression throughout a large portion of the brain, and a significantly improved behavioral performance of treated animals. Moreover, we analyzed the effect of therapy on the expression profile of some genes related to neurotrophic signaling molecules and inflammatory cytokines previously found altered in MPS IIIB mice. At 1 month from treatment, the level of cerebellin 1 (Cbln1) was decreased while the brain-derived neurotrophic factor (Bdnf) expression was increased, both reaching normal values. At 6 months from treatment a significant reduction in the expression of all the inflammation- and oxidative stress-related genes was observed, as well as the maintenance of the correction of the Bdnf gene expression. These results indicate that NAGLU delivery from intracerebral sources has the capacity to alleviate most disease manifestations in MPS IIIB mice; furthermore, Bdnf might be a response-to-therapy biomarker for MPS IIIB. © 2009 Wiley-Liss, Inc.