ENZYME REPLACEMENT AND GENE-THERAPY FOR GAUCHERS-DISEASE

The lipid storage disorders have long been considered primary candidat es for enzyme replacement therapy. This goal has been achieved with a remarkable degree of success in Gaucher's disease. Among the accomplis hments that were important to obtain clinical benefit were the develop ment of a large-scale procedure to purify human placental glucocerebro sidase and a method to target this enzyme to lipid-storing macrophages through glycoform modification. In addition, the effectiveness of rec ombinantly produced macrophage-targeted glucorerebrosidase has recentl y been demonstrated. Because macrophages originate from stem cells in the bone marrow, ex vivo transduction of these cells with retroviral v ectors containing the cDNA for human glucocerebrosidase is being explo red for the genetic therapy of Gaucher's disease.