Femoral Structure and Biomechanical Characteristics in Sanfilippo Syndrome Type-B Mice
Sanfilippo syndrome Type-B, also known as mucopolysaccharidosis IIIB (MPS IIIB), accounts for approximately one-third of all Sanfilippo syndrome patients and is characterized by a similar natural history as Type-A. Patients suffer from developmental regression, bone malformation, organomegaly, GI di...
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MDPI AG
2023-09-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/18/13988 |
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| author | Frederick James Ashby Evelyn J. Castillo Yan Ludwig Natalia K. Andraka Cong Chen Julia C. Jamieson Nadia Kabbej John D. Sommerville Jose I. Aguirre Coy D. Heldermon |
| author_facet | Frederick James Ashby Evelyn J. Castillo Yan Ludwig Natalia K. Andraka Cong Chen Julia C. Jamieson Nadia Kabbej John D. Sommerville Jose I. Aguirre Coy D. Heldermon |
| author_sort | Frederick James Ashby |
| collection | DOAJ |
| description | Sanfilippo syndrome Type-B, also known as mucopolysaccharidosis IIIB (MPS IIIB), accounts for approximately one-third of all Sanfilippo syndrome patients and is characterized by a similar natural history as Type-A. Patients suffer from developmental regression, bone malformation, organomegaly, GI distress, and profound neurological deficits. Despite human trials of enzyme replacement therapy (ERT) (SBC-103, AX250) in MPS IIIB, there is currently no FDA approved treatment and a few palliative options. The major concerns of ERT and gene therapy for the treatment of bone malformation are the inadequate biodistribution of the missing enzyme, N-acetyl-α-glucosaminidase (NAGLU), and that the skeleton is a poorly hit target tissue in ERT and gene therapy. Each of the four known human types of MPS III (A, B, C, and D) is usually regarded as having mild bone manifestations, yet it remains poorly characterized. This study aimed to determine bone mineral content (BMC), volumetric bone mineral density (vBMD), and biomechanical properties in femurs MPS IIIB C57BL/6 mice compared to phenotypic control C57BL/6 mice. Significant differences were observed in MPS IIIB mice within various cortical and cancellous bone parameters for both males and females (<i>p</i> < 0.05). Here, we establish some osteogenic manifestations of MPS IIIB within the mouse model by radiographic and biomechanical tests, which are also differentially affected by age and sex. This suggests that some skeletal features of the MPS IIIB mouse model may be used as biomarkers of peripheral disease correction for preclinical treatment of MPS IIIB. |
| first_indexed | 2024-03-10T22:40:23Z |
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| language | English |
| last_indexed | 2024-03-10T22:40:23Z |
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| publisher | MDPI AG |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-824cbd65d6b748d0b4b34c94206bdd1c2023-11-19T11:06:12ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-09-0124181398810.3390/ijms241813988Femoral Structure and Biomechanical Characteristics in Sanfilippo Syndrome Type-B MiceFrederick James Ashby0Evelyn J. Castillo1Yan Ludwig2Natalia K. Andraka3Cong Chen4Julia C. Jamieson5Nadia Kabbej6John D. Sommerville7Jose I. Aguirre8Coy D. Heldermon9Department of Medicine, University of Florida, Gainesville, FL 32611, USADepartment of Physiological Sciences, University of Florida, Gainesville, FL 32611, USADepartment of Medicine, University of Florida, Gainesville, FL 32611, USADepartment of Medicine, University of Florida, Gainesville, FL 32611, USADepartment of Orthopaedic Surgery & Sports Medicine, University of Florida, Gainesville, FL 32611, USADepartment of Medicine, University of Florida, Gainesville, FL 32611, USADepartment of Medicine, University of Florida, Gainesville, FL 32611, USADepartment of Medicine, University of Florida, Gainesville, FL 32611, USADepartment of Physiological Sciences, University of Florida, Gainesville, FL 32611, USADepartment of Medicine, University of Florida, Gainesville, FL 32611, USASanfilippo syndrome Type-B, also known as mucopolysaccharidosis IIIB (MPS IIIB), accounts for approximately one-third of all Sanfilippo syndrome patients and is characterized by a similar natural history as Type-A. Patients suffer from developmental regression, bone malformation, organomegaly, GI distress, and profound neurological deficits. Despite human trials of enzyme replacement therapy (ERT) (SBC-103, AX250) in MPS IIIB, there is currently no FDA approved treatment and a few palliative options. The major concerns of ERT and gene therapy for the treatment of bone malformation are the inadequate biodistribution of the missing enzyme, N-acetyl-α-glucosaminidase (NAGLU), and that the skeleton is a poorly hit target tissue in ERT and gene therapy. Each of the four known human types of MPS III (A, B, C, and D) is usually regarded as having mild bone manifestations, yet it remains poorly characterized. This study aimed to determine bone mineral content (BMC), volumetric bone mineral density (vBMD), and biomechanical properties in femurs MPS IIIB C57BL/6 mice compared to phenotypic control C57BL/6 mice. Significant differences were observed in MPS IIIB mice within various cortical and cancellous bone parameters for both males and females (<i>p</i> < 0.05). Here, we establish some osteogenic manifestations of MPS IIIB within the mouse model by radiographic and biomechanical tests, which are also differentially affected by age and sex. This suggests that some skeletal features of the MPS IIIB mouse model may be used as biomarkers of peripheral disease correction for preclinical treatment of MPS IIIB.https://www.mdpi.com/1422-0067/24/18/13988Sanfilippo syndromeMPS IIIBlysosomal storage diseasebonemodel |
| spellingShingle | Frederick James Ashby Evelyn J. Castillo Yan Ludwig Natalia K. Andraka Cong Chen Julia C. Jamieson Nadia Kabbej John D. Sommerville Jose I. Aguirre Coy D. Heldermon Femoral Structure and Biomechanical Characteristics in Sanfilippo Syndrome Type-B Mice International Journal of Molecular Sciences Sanfilippo syndrome MPS IIIB lysosomal storage disease bone model |
| title | Femoral Structure and Biomechanical Characteristics in Sanfilippo Syndrome Type-B Mice |
| title_full | Femoral Structure and Biomechanical Characteristics in Sanfilippo Syndrome Type-B Mice |
| title_fullStr | Femoral Structure and Biomechanical Characteristics in Sanfilippo Syndrome Type-B Mice |
| title_full_unstemmed | Femoral Structure and Biomechanical Characteristics in Sanfilippo Syndrome Type-B Mice |
| title_short | Femoral Structure and Biomechanical Characteristics in Sanfilippo Syndrome Type-B Mice |
| title_sort | femoral structure and biomechanical characteristics in sanfilippo syndrome type b mice |
| topic | Sanfilippo syndrome MPS IIIB lysosomal storage disease bone model |
| url | https://www.mdpi.com/1422-0067/24/18/13988 |
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