Recombinant DNA Advisory Committee- 9/12-13/94 
in the study. One of the reasons in deciding to include children was to assess the dose 
effect. The laboratory capacity is limited to the production of enough transduced cells to 
provide 20% of a normal circulating lymphocyte enzyme level in an adult patient. Similar 
doses of cells would have a better effect on a child since the body weight is much smaller. 
If children are treated early, there is better chance of preventing complications. 
Considering that this is a Phase I study, Dr. Whitley said he would agree to limit the 
present study to 2 adults for a 1 year period and to evaluate the data at the end of the 
study. 
This initial study is limited due to the constraint posed by the limited resources available 
to the investigators at their institution. 
Responding to Dr. Saha’s question on vector rearrangement, Dr. Whitley said Southern 
blot analysis of vector structure in transduced lymphoblastoid cell line was included in the 
submitted materials. No vector rearrangement has been observed in this system. There is 
a technical problem in performing similar analysis in the transduced peripheral blood 
lymphocytes since these cells cannot be established as cell lines for this kind of analysis. 
Regarding the Informed Consent document, revisions will be made according to the RAC 
suggestions, including clarification of the barrier contraception statement, and a clear 
statement on the 1 year limit to the study. No firm funding is yet available for the present 
study. All the testings for vector preparations are very expensive. 
Dr. Whitley agreed to limit this study to 2 adult patients, although some of his minor 
patients will be disappointed by excluding them in the trial. 
Dr. Straus inquired about patient follow-up particularly in terms of assessing how long the 
transgene will persist and what proportion of the circulating white blood cells will have the 
transgene. Dr. Whitley agreed to do so. 
Dr. Chase asked about the cost of performing this study. Dr. Whitley said that just vector 
production and testing would cost $1.6 million to treat 4 patients, and additional $200,000 
to hire a personnel to transduce the cells. Dr. Chase commented that the prohibitive cost 
of gene therapy would be a problem for wide-scale application of this form of treatment. 
Dr. Parkman said the cost would be less if a single bone marrow stem cell protocol is 
proposed. The investigators chose to perform the peripheral blood cell study first to avoid 
the anticipated tough questions of attempting a bone marrow study with children. 
Dr. Walters remarked on the cost of gene therapy. As the gene transfer technology is 
improved, it is hoped that simplified and cost effective methods will emerge out of this 
effort. 
Dr. Whitley said that patients will be informed as soon as the study information is 
obtained regarding the results of RCR testings. 
Recombinant DNA Research, Volume 20 
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