Gene therapy ameliorates cardiovascular disease in dogs with mucopolysaccharidosis VII.
Circulation
; 110(7): 815-20, 2004 Aug 17.
Article
em En
| MEDLINE
| ID: mdl-15289379
ABSTRACT
BACKGROUND:
Mucopolysaccharidosis VII (MPS VII) is a lysosomal storage disease caused by deficient beta-glucuronidase (GUSB) activity resulting in defective catabolism of glycosaminoglycans (GAGs). Cardiac disease is a major cause of death in MPS VII because of accumulation of GAGs in cardiovascular cells. Manifestations include cardiomyopathy, mitral and aortic valve thickening, and aortic root dilation and may cause death in the early months of life or may be compatible with a fairly normal lifespan. We previously reported that neonatal administration of a retroviral vector (RV) resulted in transduction of hepatocytes, which secreted GUSB into the blood and could be taken up by cells throughout the body. The goal of this study was to evaluate the effect on cardiac disease. METHODS ANDRESULTS:
Six MPS VII dogs were treated intravenously with an RV-expressing canine GUSB. Echocardiographic parameters, cardiovascular lesions, and biochemical parameters of these dogs were compared with those of normal and untreated MPS VII dogs.CONCLUSIONS:
RV-treated dogs were markedly improved compared with untreated MPS VII dogs. Most RV-treated MPS VII dogs had mild or moderate mitral regurgitation at 4 to 5 months after birth, which improved or disappeared when evaluated at 9 to 11 and at 24 months. Similarly, mitral valve thickening present early in some animals disappeared over time, whereas aortic dilation and aortic valve thickening were absent at all times. Both myocardium and aorta had significant levels of GUSB and reduction in GAGs.
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Base de dados:
MEDLINE
Assunto principal:
Doenças Cardiovasculares
/
Terapia Genética
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Mucopolissacaridose VII
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Vetores Genéticos
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Glucuronidase
Idioma:
En
Ano de publicação:
2004
Tipo de documento:
Article