Gene therapy for cardiovascular manifestations of lysosomal storage diseases.

Cardiac disease causes morbidity in several lysosomal storage diseases, which are the result of deficient activity of lysosomal enzymes. Mucopolysaccharidosis (MPS) causes aortic and valvular disease, Pompe disease causes cardiac muscle weakness, and Fabry disease causes left ventricular hypertrophy. Enzyme replacement therapy involves intravenous injection of enzyme modified with mannose 6-phosphate, which can be taken up by cells, and is currently approved for some lysosomal storage diseases. Gene therapy can result in secretion of mannose 6-phosphate-modified enzyme into blood, from where it can; similarly, be taken up by cells. Gene therapy has been effective in animal models of lysosomal storage disease, and holds great promise.