Recombinant DNA Advisory Committee - 2/10-11/92 
the investigators decided it would be inappropriate to use a different patient population, 
especially given the small number of children with this disease. 
Dr. Mclvor said that the preclinical data provided by the investigators does not really 
address gene transfer into stem cells, which are supposed to generate lymphocyte lineage. 
Further, there was no information on expression of the ADA gene. Dr. Anderson agreed 
that there are no conclusive animal data, but that any corrected cell that is inserted into a 
patient would have a positive advantage. The only real data would come from patients. 
ADA patients constitute the only real model system because there is no animal model for 
ADA deficiency. 
Dr. Leventhal stated that the investigators were decreasing their chances of determining 
efficacy by continuing to use the original patients and by continuing to use the peripheral 
T lymphocytes to which these patients have already responded. This procedure should be 
used in patients whose immune system has not already been reconstituted. Dr. Anderson 
stated that this protocol is intended for new patients, and requested the RAC not to 
restrict the investigators by demanding that the previously treated two patients not be 
treated until the protocol is completed on other new patients. The clinical process is one 
that involves incremental steps of increasing knowledge. 
Dr. Culver stated that the original ADA protocol was designed around many of the same 
dilemmas. The investigators did not know if the transduced T lymphocytes would function 
since the patients were on PEG-ADA. When the investigators suggested terminating the 
PEG- ADA and examining how the T lymphocytes functioned alone, the RAC would not 
approve this proposed change. This amended protocol will raise the same issues. If there 
are patients that respond to treatment with stem cells, T lymphocytes, or both, the 
investigators will ask the RAC for permission to terminate PEG-ADA treatment. Since 
there is not a large pool of patients with ADA deficiency, the investigators are limited to 
studying each patient and his/her immunologic reconstitution over time. This disease is a 
heterogeneous disorder. 
Committee motion 
Dr. Carmen moved to approve the amendment to Appendix D-XV of the NIH Guidelines. 
Dr. Post seconded the motion. 
Dr. Mclvor stated that he was not going to vote in favor of the motion since he had 
concerns about insufficient evidence that the ADA gene would be expressed in the cell 
lineages as predicted by the investigators. Dr. Hirano asked if the investigators would be 
able to obtain this expression data. Dr. Mclvor said the investigators should demonstrate 
that gene transfer into the cell population has been effectively achieved, and that this 
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