Mucopolysaccharidosis VII (MPS VII) is due to deficient activity of the 
lysosomal enzyme β-glucuronidase (GUSB) and results in the accumulation of 
glycosaminoglycans (GAGs). This study determined the long-term effect of 
neonatal intravenous injection of a gamma retroviral vector (RV) on cardiac 
valve disease in MPS VII dogs. Transduced hepatocytes secreted GUSB into the 
blood for up to 11 years at levels similar to or greater than those achieved 
with enzyme replacement therapy (ERT). Valve regurgitation and thickening were 
scored from 0 (normal) to +4 (severely abnormal). At 1 year, untreated MPS VII 
dogs had mitral regurgitation, mitral valve thickening, aortic regurgitation, 
and aortic valve thickening scores of 2.3 ± 0.7, 2.3 ± 0.6, 1.8 ± 0.5, and 1.6 ± 
0.7, respectively, which were higher than the values of 0.6 ± 0.1, 0.1 ± 0.4, 
0.3 ± 0.8, and 0.1 ± 0.4, respectively, in treated MPS VII dogs. Treated MPS VII 
dogs maintained low aortic regurgitation and aortic valve thickening scores in 
their lifetime. Although mitral regurgitation and mitral valve thickening scores 
increased to 2.0 at ≥ 8 years of age in the treated MPS VII dogs, older normal 
dogs from the colony had similar scores, making it difficult to assess mitral 
valve disease. Older treated dogs had calcification within the mitral and the 
aortic valve annulus, while GUSB staining demonstrated enzyme activity within 
the mitral valve. We conclude that neonatal RV-mediated gene therapy reduced 
cardiac valve disease in MPS VII dogs for up to 11 years, and propose that 
neonatal initiation of ERT should have a similar effect.