Human Gene Therapy Subcommittee - July 29-30, 1991 
these patients first. Obviously, when the treatment proves to be efficacious and 
reasonably safe, treatment would be made available to children with FH. The consent 
form is not clear and needs to be revised. The investigator may want to consider a 
serial process of consent. 
Ms. Meyers stated that the children's consent form is very negative. It explains why a 
child should not participate, and it does not supply any information regarding the 
possible benefits. She suggested that the following phrase be added: "We do hope that 
you will benefit and that other patients may benefit in the future," so that the patients 
may feel that their participation in this study will be of benefit to others. This is a very 
rare disease, and many of the patients die before they reach adolescence. To deny 
children the opportunity for this treatment would not be reasonable. 
Dr. D. Miller said that hepatocytes from children are more likely to be transduced than 
hepatocytes from adults. Mr. Capron said that because this disease affects children as 
well as adults, the safety and efficacy of the treatment first should be determined in 
adults. Dr. Parkman said that treating adults before children is discriminatory against 
children. Dr. Leventhal added that the children selected for this protocol should be as 
sick as adults. Patients need to be symptomatic before they are selected. The only 
other option for these children might be a liver transplant. However, they might not 
receive the transplant because of the cost issue, whereas they could participate in this 
clinical protocol free of charge. There are very strong positive pressures for 
symptomatic children entering into this study. 
Mr. Capron said if markedly beneficial results are achieved in adults, the treatment of 
children could be initiated. If it takes 10 or 15 years to obtain results, this would be a 
different situation. He asked Dr. Wilson to explain the results he expects if the 
treatment is successful in relation to the issue of patient selection. 
Dr. D. Miller said that the data on the packaging cell line should be supplied to the 
HGTS prior to the FDA review. He added that the subcommittee should not have 
such a cavalier attitude toward this new vector. The Points to Consider for the Design 
and Submission of Protocols for the Transfer of Recombinant DNA into the Genome of 
Human Subjects requires a construction scheme, as well as information on how these 
vectors were derived, where the sequences came from, and the sequence of the final 
product. The investigators did not supply the sequence information. Dr. Wilson 
replied that the entire vector is currently being sequenced by an FDA-approved 
laboratory as part of the evaluation process. 
Dr. Mclvor agreed that it is necessary to have sequence information on the different 
elements of a vector that is under consideration. Once a virus is integrated into the 
target cell, the hkelihood of insertional mutagenesis must be determined. Since it is a 
new cell line, the investigators should provide a list of assays that have been performed 
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Recombinant DNA Research, Volume 14 
