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Gene therapy ameliorates cardiovascular disease in dogs with mucopolysaccharidosis VII.

M M Sleeper1, B Fornasari, N M Ellinwood

  • 1Department of Clinical Studies, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. sleeper@vet.upenn.edu

Circulation
|August 4, 2004

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View abstract on PubMed

Summary

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  • Agricultural, Veterinary And Food Sciences
  • Veterinary Sciences
  • Veterinary Medicine (excl. Urology)
  • Gene Therapy Ameliorates Cardiovascular Disease In Dogs With Mucopolysaccharidosis Vii.
    • This summary is machine-generated.

    Gene therapy using a retroviral vector (RV) significantly improved cardiac function in dogs with Mucopolysaccharidosis VII (MPS VII). RV treatment reduced glycosaminoglycan (GAG) accumulation, improving heart valve and aortic health in MPS VII dogs.

    Area of Science:

    • Biochemistry
    • Genetics
    • Veterinary Medicine

    Background:

    • Mucopolysaccharidosis VII (MPS VII) is a genetic lysosomal storage disease due to beta-glucuronidase (GUSB) deficiency.
    • GAG accumulation in cardiovascular cells causes severe cardiac disease, a primary cause of mortality in MPS VII.
    • Previous studies showed neonatal retroviral vector (RV) gene therapy transduced hepatocytes, leading to systemic GUSB secretion.

    Purpose of the Study:

    • To evaluate the efficacy of RV-mediated GUSB gene therapy on cardiac manifestations in MPS VII dogs.
    • To assess the impact of GUSB gene therapy on GAG levels in cardiac tissues.

    Main Methods:

    • Six MPS VII dogs received intravenous administration of an RV expressing canine GUSB.
    • Echocardiographic parameters, cardiovascular lesions, and biochemical markers were compared between treated MPS VII dogs, untreated MPS VII dogs, and normal dogs.

    Main Results:

    • RV-treated MPS VII dogs showed marked improvement in cardiac function compared to untreated controls.
    • Mitral regurgitation and mitral valve thickening significantly improved or resolved over time in treated dogs.
    • Aortic dilation and aortic valve thickening were prevented, and myocardial and aortic GAG levels were reduced.

    Conclusions:

    • Intravenous RV gene therapy is effective in ameliorating cardiac disease in MPS VII.
    • The treatment leads to sustained GUSB expression and GAG reduction in cardiac tissues.
    • This approach offers a promising therapeutic strategy for MPS VII-related cardiac complications.

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