کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10833005 | 1065780 | 2013 | 11 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
The effect of neonatal gene therapy on skeletal manifestations in mucopolysaccharidosis VII dogs after a decade
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کلمات کلیدی
human α1-antitrypsin(SD)(MMP)(TNFα)(IV)β-glucuronidase - β-گلوکورونیدازenzyme replacement therapy - آنزیم جایگزین درمانstandard deviation - انحراف معیارRetroviral vector - بردار RetroviralDegenerative joint disease - بیماری مفصلی تخریب شدهtumor necrosis factor α - تومور نکروز عامل αLong-terminal repeat - تکرار طولانی مدتIntravenous - داخل وریدیDog - سگHepatocyte growth factor - عامل رشد هپاتوسیتmatrix metalloproteinase - ماتریکس متالوپروتئینازmannose 6-phosphate - مانوس 6-فسفاتMucopolysaccharidosis - موکوپلیساکاریدوزHematopoietic stem cell transplantation - پیوند مغز استخوانdysostosis multiplex - چندتایی دیستواستاتGene therapy - ژن درمانیGlycosaminoglycans - گلیکوز آمینو گلیکان هاToll-like receptor 4 - گیرنده تله مانند 4
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله

چکیده انگلیسی
Mucopolysaccharidosis (MPS) VII is a lysosomal storage disease due to deficient activity of β-glucuronidase (GUSB), and results in glycosaminoglycan accumulation. Skeletal manifestations include bone dysplasia, degenerative joint disease, and growth retardation. One gene therapy approach for MPS VII involves neonatal intravenous injection of a gamma retroviral vector expressing GUSB, which results in stable expression in liver and secretion of enzyme into blood at levels predicted to be similar or higher to enzyme replacement therapy. The goal of this study was to evaluate the long-term effect of neonatal gene therapy on skeletal manifestations in MPS VII dogs. Treated MPS VII dogs could walk throughout their lives, while untreated MPS VII dogs could not stand beyond 6 months and were dead by 2 years. Luxation of the coxofemoral joint and the patella, dysplasia of the acetabulum and supracondylar ridge, deep erosions of the distal femur, and synovial hyperplasia were reduced, and the quality of articular bone was improved in treated dogs at 6 to 11 years of age compared with untreated MPS VII dogs at 2 years or less. However, treated dogs continued to have osteophyte formation, cartilage abnormalities, and an abnormal gait. Enzyme activity was found near synovial blood vessels, and there was 2% as much GUSB activity in synovial fluid as in serum. We conclude that neonatal gene therapy reduces skeletal abnormalities in MPS VII dogs, but clinically-relevant abnormalities remain. Enzyme replacement therapy will probably have similar limitations long-term.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Molecular Genetics and Metabolism - Volume 109, Issue 2, June 2013, Pages 183-193
Journal: Molecular Genetics and Metabolism - Volume 109, Issue 2, June 2013, Pages 183-193
نویسندگان
Elizabeth M. Xing, Van W. Knox, Patricia A. O'Donnell, Tracey Sikura, Yuli Liu, Susan Wu, Margret L. Casal, Mark E. Haskins, Katherine P. Ponder,