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GTI 0101 (04/08/93) 
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PROTOCOL SYNOPSIS 
Retroviral Mediated Transfer of the cDNA for Human Glucocerebrosidase into 
Hematopoietic Stem Cells of Patients with Gaucher Disease 
Genetic Therapy, Inc. 
This is a Phase I Study to investigate the feasibility and safety of transferring 
glucocerebrosidase (GC) cDNA into hematopoietic stem cells of patients with 
Gaucher disease which is a genetic disorder characterized by the accumulation of 
glucocerebroside. 
Patients J> 18 years of age with Gaucher disease. 
10 evaluable patients 
A. First treatment cycle consists of bone marrow (BM) harvest OR mobilized 
peripheral blood stem cell (PBSC) harvest. 
1. Conventional marrow harvest is used; OR 
2. PBSC harvest: 
a. G-CSF: 10 /xg/kg/day (IX) SQ for 7 days 
b. PBSC harvested days 5, 6, and 7 from patient and processed. 
B. BM or PB cells enriched for CD34 + cells enriched with immunoabsorption 
column (CellPro Inc.) 
C. Cells transduced with Gc vector-containing supernatant. 
D. Cells reinfused into patient. 
E. <_ 4 cycles of PBSC transduced cells, no more frequent than every 2 months. 
No further cycles if first cycle was bone marrow harvest. 
1. Development of high grade toxicities or intolerances. 
2. Expression of GC enzyme levels equivalent to normal patients 
• To investigate whether the cDNA encoding human glucocerebrosidase can be 
safely transferred to hematopoietic stem cells by retroviral mediated gene transfer. 
• To determine the extent of engraftment after autologous transplantation of 
transduced hematopoietic stem cells into individuals with Gaucher disease without 
prior ablation (partial or complete) of endogenous marrow. 
• To investigate whether the transferred human glucocerebrosidase cDNA will 
be expressed in monocytes/macrophages at levels that might be expected to be 
beneficial. 
• To investigate the effect of repeated transplantation of transduced PBSC into 
Gaucher disease patients on the fraction of monocyte/macrophages containing and 
expressing glucocerebrosidase. 
Donald Kohn, MD, Stefan Karlsson, MD 
[790] 
Recombinant DNA Research, Volume 17 
