Recombinant DNA Advisory Committee - 12/2-3/93 
(GC) production results in the accumulation of glucocerebrosides. Current therapy 
consists of periodic injections of the purified human enzyme. This enzyme is found 
principally in small amounts in the placenta. The cost of treatment for a typical affected 
adult approaches $400,000 per year. Since enzyme replacement therapy has been 
demonstrated to alleviate symptoms in Gaucher patients, gene therapy is a logical next 
approach. The investigators propose to collect autologous peripheral blood cells, isolate 
CD34( + ) stem cells (which are capable of repopulating bone marrow), and transduce 
these cells with a retroviral vector containing the human GC gene. These transduced 
cells will then be reinfused into the patient. Dr. Haselkom asked the investigators to 
provide additional information about the level of GC expression by transduced CD34( + ) 
cells. How does the level of GC expression observed by the investigators compare to the 
levels of expression observed by Drs. Barranger (University of Pittsburgh) and Karlsson 
(NIH)? Have experiments been performed comparing the proposed vector with the 
other two RAC-approved GC vectors? Commercial considerations should be ignored so 
that the optimum vector is proposed for all trials. Dr. Haselkom expressed concern 
about the RACs recommendation for approval of 3 simultaneous trials for the same 
disease. Preferably, the RAC should wait to obtain results from the ongoing studies 
before approving additional trials. Dr. Haselkom noted that Dr. Schuening has not 
accmed any patients onto either of his previously approved trials for breast cancer and 
lymphoid malignancies. 
Review-Dr. Brinckerhoff 
Dr. Brinckerhoff stated that the current forms of therapy for Gaucher's disease, enzyme 
replacement and bone marrow transplantation, have shortcomings. Therefore, there is 
significant rationale for proposing gene therapy as a treatment for this disease. Although 
the investigators have conducted several preliminary in vivo and in vitro experiments, the 
data are diffuse and inconclusive. Dr. Brinckerhoff asked about the level of gene 
expression necessary to demonstrate efficacy in the humans. Although the investigators 
have demonstrated GC gene expression in fibroblasts, it is unclear how this data 
extrapolates to humans. Preliminary data does not demonstrate the duration and level of 
GC expression. Although long-term expression of the neomycin resistance (neo R ) gene 
was demonstrated using the proposed vector, the investigators were unable to co- 
transfect the ADA gene. Data has not been provided demonstrating long-term GC 
expression. Although the murine data were encouraging, the canine experiments were 
inadequate. Quality assurance data on the modified retrovirus vector, LgGC, and the 
packaging cells are inadequate. Is a 15 to 20% correction of the GC enzyme activity in 
these patients sufficient to alleviate the clinical symptoms? Will the investigators be able 
to achieve the proposed level of gene expression? Dr. Brinckerhoff recommended 
deferral of this protocol until the RAC has had the opportunity to review additional 
expression data. 
Review-Dr. Carmen 
Dr. Carmen stated that the only novel feature about this study over the previously 
approved Gaucher's disease protocols is that a new retrovirus vector, LgGC, is being 
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Recombinant DNA Research, Volume 18 
