June 1, 1990, Human Gene Therapy Subcommittee Minutes 
ADA bone marrow and the only cells which will be normalized will be the T and B cells; 
the red cells, monocytes, and everything everywhere else in the body remains ADA- 
deficient. By detoxifying the entire body pool of deoxyadenosine, the levels inside the T 
cells are lowered. Therefore, the most direct method for treatment is to put the enzyme 
directly into cells since that is most analogous to successful transplantation. 
Dr. R. Murray said he agreed with Dr. Epstein. Dr. R. Murray made a motion that the 
period remaining before lunch recess should be used to formulate specific questions. He 
asked that the recess be extended by 15 or 20 minutes to allow subcommittee members a 
chance to finish reading some of the material. 
Dr. Epstein said he did not believe it required a motion but that the Chair could take 
this under advisement. Dr. Walters said it seemed like a very good strategy. Ms. Areen 
said she agreed with that strategy of using this time to formulate questions. She said the 
two areas she felt were important to discuss were the issues of patient selection and the 
communication of risk to the parents. Dr. Leventhal added that she wanted more 
quantitative data on immune function and achievable levels of ADA and was interested 
in knowing what rules had been put in place for an early cessation of the study. 
Dr. Parkman said that patient selection should fall into two groups, stable and non-stable 
patients. As far as outcome variables, they should be assessed at the cellular and 
molecular level, similar to the studies performed in Milan, looking at level of function 
and whether the production of IL-2 by the cells is relevant. Dr. Parkman felt it was 
important for the subcommittee to decide whether the Milan data would have to be 
reproduced by the investigators. Lastly, he said long-term variables are important and 
need to be clearly defined. 
Dr. Neiman said he would like to have a response from the investigators on whether 
transduced cells that are infused can be followed for periods of time and whether this 
should be set up in the form of an oncogenicity testing system. 
Dr. Kelley said that half-life of the transduced cell was important and wanted to know 
the half-life of the ADA genetically modified cells in circulation. 
Dr. Zallen said that she felt it was important to communicate to patients the implications 
of the long-term treatment in relation to costs that the patient would have to absorb in 
terms of travel or availability to investigators over time. Also, patients entered into the 
protocol would be followed indefinitely. If long-term provision of PEG-ADA was being 
proposed, she wondered how firm such a promise should be in light of future advances 
which could make this technique less desirable. Conceivably there are circumstances 
which could lead to the discontinuation of such an option for patients. 
Dr. R. Murray called attention to the statement on page 88 of the protocol relevant to 
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Recombinant DNA Research, Volume 14 
