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It is not anticipated that this study will have a sufficient therapeutic benefit to the patient 
to permit the removal of enzyme replacement therapy immediately, but it is possible that 
the Gaucher disease patients involved in the study will express significant amounts of 
glucocerebrosidase to permit the consideration of discontinuing enzyme replacement 
therapy. The study is expected to assist in the development of gene therapy for Gaucher 
disease so it will be unnecessary to continue enzyme replacement therapy. This study 
represents a step towards reaching that goal. 
1.51 Biology of reconstitution following autologous transplantation of bone marrow or 
peripheral blood stem cells 
As is true in all genetic marking protocols or gene therapy protocols, very little can be 
learned if marking is completely unsuccessful, and no transduced cells can be identified 
either short or long term after transplantation and engraftment. The previously described 
experimental data imply that significant transduction will occur. What is not as fully 
tested in humans is the ability to engraft early hematopoietic progenitor and stem cells 
in individuals without prior ablative therapy. The ability to perform autologous marrow 
transplantation with gene altered marrow without ablative therapy would greatly enhance 
the use of gene transfer techniques to study and treat human disease. The proposed 
protocol is designed to provide information about the biology of reconstitution following 
autologous transplantation. 
1.6 Objectives 
1.61 To investigate whether the cDNA encoding human glucocerebrosidase can be 
safely transferred to hematopoietic stem cells by retroviral mediated gene transfer. 
1.62 To determine the extent of engraftment after autologous transplantation of 
transduced hematopoietic stem cells into Gaucher disease patients without prior 
ablation (partial or complete) of recipient marrow. 
1.63 To investigate the whether the transferred human glucocerebrosidase cDNA will 
be expressed in monocytes/macrophages at levels that might be expected to be of 
therapeutic benefit. 
1 .64 To investigate the effect of repeated transplantation of transduced peripheral blood 
stem cells into individuals with Gaucher disease upon the fraction of 
monocyte/macrophages containing and expressing glucocerebrosidase. 
Recombinant DNA Research, Volume 17 
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