Gene transfer therapy of gaucher disease

Abstract

Gaucher disease is a hereditary disorder of glycosphingolipid metabolism caused by deficiency of lysosomal glucocerebrosidase (GBA) and characterized by accumulation of glucocerebroside in macrophages of the mononuclear phagocyte system (MPS; also called the reticuloendothelial system). Enzyme replacement treatment of the disease is highly effective; however, it is extremely expensive and inconvenient. Attempts at genetic correction by gene transfer therapy in patients with Gaucher disease are currently under investigation. All recently approved clinical trial protocols involve ex vivo transduction of hematopoietic stem cells by murine retrovirus vectors containing human GBA cDNA. We are currently exploring the potential efficacy of in vivo gene transfer strategies for correction of the defect in Gaucher disease, using GBA incorporated into cationic liposomes and infused intravenously in mice.