Cardiovascular manifestations of
lysosomal storage disease (
LSD) are a significant health problem for affected patients. Infantile-onset
cardiac disease, because of its rapid progression, is usually treated symptomatically.
Therapy in older patients includes valve replacement and bone marrow (BM)
transplantation, both of which are life threatening in the already debilitated patients.
Enzyme replacement therapy has potential benefit but has not yet been demonstrated to provide long-term relief for
cardiac disease. Here, we demonstrate prevention of severe cardiac manifestations in
beta-glucuronidase (GUSB) null mice BM-transplanted i.v. as neonates without myeloablative pretreatment. The mice, a model of
mucopolysaccharidosis type VII (MPSVII,
Sly syndrome), develop progressive
LSD unless provided with GUSB early in life. The BM recipients retained GUSB+ donor cells in the peripheral blood and heart until necropsy at > or = 11 months of age. The
enzyme beta-hexosamindase increased in tissues of GUSB null MPSVII mice was reduced significantly (P = 0.001) in treated MPSVII hearts. Electrocardiography demonstrated normalization of heart rate, PR, PQ, and QRS intervals in BM recipients. Storage was markedly reduced in the stroma of heart valves, adventitial cells of the aortic root, perivascular and interstitial cells of the myocardium, and interstitial cells of the conduction tissue. Heart/
body weight ratio normalized. The aortic root was still grossly distended, and the conductive myocytes retained storage, suggesting neither plays a major role in ECG normalization. We conclude that
transplantation of MPSVII neonates without toxic intervention can prevent many of the cardiovascular manifestations of
LSD.