APPENDIX E: Scientific Abstract 
Scientific Abstract 
Gaucher’s disease is the most frequent sphingolipid storage disorder and affects about 
30,000 patients in the United States. It is an autosomal recessive hereditary deficiency of a 
lysosomal enzyme, glucocerebrosidase, required for glycolipid degradation. The absence of a 
functional glucocerebrosidase leads to accumulation of glucosylcerebroside in macrophages 
throughout the reticular endothelial system. This lipid storage typically leads to 
hepatosplenomegaly, hypersplenism and lytic bone lesions. 
The purpose of this study is to investigate whether ex vivo retrovirus-mediated transfer 
of the cDNA for human glucocerebrosidase into peripheral blood repopulating cells of patients 
with Type 1 Gaucher’s disease followed by infusion of the transduced cells into the patient is 
safe and able to improve or cure the disease. Peripheral blood repopulating cells will be 
mobilized by treatment of the patient with recombinant human granulocyte colony-stimulating 
factor collected by repeated leukapheresis and selected for CD34 positive cells by 
avidin-biotin-immunoadsorption. CD34 positive cells will then be transduced ex vivo over a 
5-day period in a long-term marrow culture system containing medium with retrovirus 
supernatant. After transduction, cells will be infused into the patient without myeloablative 
treatment. Collection, transduction and infusion of transduced peripheral blood cells will be 
repeated two times at 2-month intervals to increase the amount of transduced repopulating cells 
transplanted. 
The primary endpoint of this study is to examine the safety of infusing peripheral blood 
repopulating cells transduced with the human glucocerebrosidase cDNA. The persistence and 
expression of the glucocerebrosidase gene in hematopoietic cells after infusion will also be 
studied. 
Recombinant DNA Research, Volume 18 
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