#838.0 
FRED HUTCHINSON CANCER RESEARCH CENTER 
UNIVERSITY OF WASHINGTON SCHOOL OF MEDICINE 
DEPARTMENT OF MEDICINE, DIVISION OF ONCOLOGY 
(10/05/93) 
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1. Retrovirus-Mediated Transfer of the cDNA for Human Glucocerebrosidase into Peripheral 
Blood Repopulating Cells of Patients with Gaucher’s Disease. 
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Principal Investigator: Friedrich Schuening, M.D., Assistant Member, FHCRC (667-4410). 
1 Associates: Jean Sanders, M.D., Professor of Pediatrics, UW, Member, FHCRC (667-4348); C. Ronald 
Scott, M.D., Professor of Pediatrics, UW (548-3370); Rainer Storb, M.D., Professor of Medicine, UW, 
Member, FHCRC (667-4407); A. Dusty Miller, Ph.D., Affiliate Associate Professor of Pathology, UW, 
Member, FHCRC (667-2890); John A. Barranger, M.D., Ph.D., Professor of Pediatrics, University of 
i Pittsburgh; William Bensinger, M.D., Associate Professor of Medicine, UW, Associate Member, 
FHCRC; Scott Rowley, M.D., Associate Member, FHCRC; Ted Gooley, Ph.D., Assistant Member, 
FHCRC; Hans-Peter Kiem, M.D., Fellow, FHCRC; Christof von Kalle, M.D., Visiting Scientist, 
! FHCRC; Fred Appelbaum, M.D., Professor of Medicine, Member/Clinical Director, FHCRC. 
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Phone: Working Hours (206) 667-4410; Emergency (24 hour) Phone: 667-5001 
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2. Introduction 
The purpose of this study is to investigate whether ex vivo retrovirus-mediated transfer of the 
cDNA for human glucocerebrosidase (GC) 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 (PBRC) will be mobilized by 
treatment of the patient with recombinant human granulocyte colony stimulating factor (rhG-CSF), 
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. 
3. Background 
A. Pathophysiology of Gaucher’s Disease 
Gaucher’s disease, the most frequent sphingolipid storage disorder, is an autosomal 
recessive hereditary deficiency of a lysosomal enzyme required for glycolipid degradation 
(1-3). The absence of a functional glucocerebrosidase (or beta glucosidase or 
glucosylceramidase), which cleaves the glucosyl group from the ceramide, leads to 
accumulation of this glucosylcerebroside in macrophages throughout the reticular 
endothelial system (RES) (4). This lipid storage typically leads to hepatosplenomegaly, 
hypersplenism and lytic bone lesions. Incidence, age of onset and clinical course 
differentiate three major types of Gaucher’s disease: the chronic adult type (type 1) that 
usually spares the CNS, the neuronopathic varieties of the acute infantile type 2 and the 
subacute type 3 disease. In contrast to type 1, types 2 and 3 manifest in infancy and 
early childhood with a rapidly deteriorating, eventually fatal course. While types 2 and 3 
occur sporadically and are extremely rare, the non-neuronopathic type 1 has an 
approximate frequency of the heterozygous state of 1 in 37 in the Ashkenazi Jewish 
Recombinant DNA Research, Volume 18 
[661] 
