Recombinant DNA Advisory Committee - 10/7-8/91 
Dr. Kelley noted for the record that Dr. Wilson got his Ph.D. in his laboratory and is a 
close personal friend. With regards to the treatment of children, there are a number of 
pediatricians on the subcommittee who thought that it is not appropriate to exclude 
children if there is reason to believe that they would be good candidates for the protocol. 
Secondly, there was concern expressed at the subcommittee meeting about restricting the 
kinds of patients who would be able to participate in this protocol. Too much restriction 
would make the treatment less likely to be successful. Thirdly, there was a discussion 
that children may be better candidates since their average life expectancy is only 10 or 
12 years; the sick patients are children. Fourthly, there was discussion that the livers 
from the younger children might actually respond better to this therapy than the livers of 
older patients. 
Dr. Miller stated that it would be interesting to look at an analogous situation, that of 
human growth hormone deficiency. In his work at the FDA, he faces a dilemma when 
overseeing the testing of the recombinant human growth hormone. In patients who are 
completely deficient in the gene for growth hormone, neutralizing antibodies are 
produced to the recombinant human growth hormone. It is likely that a spectrum of 
immune responses to the LDL receptor protein will also occur in the FH patients. That 
has implications for the question of whether to use receptor deficient or receptor 
negative patients. Those who are receptor negative are likely never to have seen the 
LDL receptor protein and are more likely to mount an immune response. However, 
negative patients are likely to have the greatest clinical benefit and whose mortality and 
morbidity would be the greatest. He suggested that the investigators include both groups 
because of the potential knowledge to be gained. However, keep them statistically 
separate so that any differential effects, both in efficacy and in immune response, can be 
observed. 
Dr. Leventhal said this disease should be thought of as a childhood disease, i.e., like 
Adenosine Deaminase (ADA) deficiency. If one insisted on doing ADA deficiency 
experiments in adults, one would never be able to do the experiments. The risk in a 
child with FH, who has a lot of stigmata of the disease at age 4, of having this procedure 
done is a great deal less than by the time the child reaches the age of 12 or 13, when 
coronary artery disease is pronounced. The risk of anesthesia and the procedure itself 
goes up with each year that one lives with the disease. The committee could place a 
medical restriction on the protocol that the serum cholesterol be a certain level for a 
certain number of years before the procedure can be initiated. Such a disease severity 
criterion instead of age criterion is reasonable. 
Dr. Wilson responded that FH is a devastating disease that has encouraged the 
development of gene therapy technology. He described a patient, Stormy Jones, a young 
girl who had FH. Homozygous FH is extremely rare; there are approximately 100 
Recombinant DNA Research, Volume 15 
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