RETROVIRAL-MEDIATED TRANSFER OF THE CDNA FOR HUMAN GLUCOCEREBROSIDASEINTO HEMATOPOIETIC STEM-CELLS OF PATIENTS WITH GAUCHER DISEASE - A PHASE-I STUDY

Patients with Gaucher disease suffer from a lack of functional glucoce rebrosidase enzyme (Gc). Disease symptoms are a result of macrophage e ngorgement secondary to this enzyme deficiency. This study is designed to determine if cDNA encoding normal Gc can be introduced into macrop hage precursors using a retroviral vector. CD34(+) cells obtained from G-CSF mobilized peripheral blood stem cells or from bone marrow will be transduced ex vivo using one of the following three methods of tran sduction: 1) (G)lGc retroviral supernatant in the presence of autologo us stroma over a period of 72 hours, 2) GlGc retroviral supernatant in the presence of interleukin-3 interleukin-6, stem cell factor and aut ologous stroma over a 72 hour period, 3) GlGc retroviral supernatant i n the presence of interleukin-3, interleukin-6, and stem cell factor o ver a 72 hour period. These transduced cells will be reinfused into th e patient and the patient monitored for toxicities as well as evidence of successful gene transfer and expression. A total of twenty-four pa tients will be enrolled on the protocol. Patients will be assigned in equal numbers to each of six groups. The two sites participating are t he National Institutes of Health and Childrens Hospital of Los Angeles .