Recombinant DNA Advisory Committee - 06/7-8/93 
to assess the success of engraftment. Animal studies indicate that a small correction of 
functional GC enzyme activity results in a therapeutic response. Dr. Smith asked 
whether the results obtained from two patients will conclusively indicate whether 
myeloablation is necessary for the remaining patients. Dr. Barranger responded that the 
first two patients will be evaluated after the first transplantation with CD34( + ) cells; and 
if necessary, the procedure will be repeated until sufficient GC expression is 
demonstrated. Animal experiments demonstrate engraftment without myeloablative 
therapy. Dr. Barranger stated that he plans to treat patients without myeloablation. 
Several RAC members questioned whether this stopping rule is explicitly written in the 
protocol. Dr. Barranger clarified the flow sheet in the protocol and said that if the first 
two patients succeed in the transplant, then the remaining patients will not receive 
myeloablation. 
Responding to Ms. Meyers' question about the exclusion of children. Dr. Barranger said 
that it is desirable to obtain results in adult patients first before considering the 
treatment of children. Dr. Barranger agreed to revise the Informed Consent document 
regarding contraception for men and women, a request for autopsy, and other minor 
changes suggested by Ms. Meyers. 
Dr. Barranger stated that some patients will receive GC enzyme replacement therapy. 
The exogenous enzyme will not interfere with measurement of the gene-expressed 
enzyme level in the peripheral blood. He agreed to include a statement in the protocol 
explaining that the enzyme therapy will not be terminated until engraftment has been 
demonstrated. Dr. Krogstad asked whether anti-GC antibodies will react with the 
enzyme produced by genetically corrected leukocytes? Dr. Barranger responded that this 
issue has not been addressed and agreed to revise the protocol to exclude patients who 
have anti-GC antibodies. Dr. Miller was concerned that if myeloablation is to be 
considered for this protocol, large animal experiments should be performed. Dr. Smith 
suggested that the protocol should be amended to eliminate the myeloablation 
procedure. The PI should resubmit a request for RAC review if myeloablation is to be 
considered. Dr. Barranger agreed to this stipulation. 
Committee Motion 
A motion was made by Dr. Haselkorn and seconded by Dr. Motulsky to approve the 
protocol with the following stipulations: (1) a maximum of 5 patients will be entered 
onto the study, (2) patients will not receive cyclophosphamide ablation of bone marrow, 
(3) patients who demonstrate antibodies against GC will not be eligible for the protocol, 
(4) GC enzyme replacement therapy will not be discontinued until cytochemical evidence 
of engraftment is demonstrated, and (5) the Informed Consent document will be revised 
to include a recommendation that male/female patients use contraception and females 
not be pregnant or plan to become pregnant while participating in the study, an 
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Recombinant DNA Research, Volume 17 
