Recombinant DNA Advisoiy Committee - 10/7-8/91 
involves taking a receptor-negative patient from zero to 5 %. The receptor-negatives, 
whatever their age, are more important in terms of potential benefit. A younger group 
of patients is preferable because it is easier to isolate, propagate, and more importantly 
to transduce younger hepatocytes. This is true in the limited human experiments, as well 
as in the animal studies. The analysis of the immunologic consequences is one of the 
most important aspects in the treatment of these patients. This information would be 
extremely helpful in the subsequent design of other experiments. He pointed out that 
the University of Michigan's transplant immunologists will participate in the protocol 
because it is possible that the receptor-negatives will develop an immune response. 
Ms. Buc asked if the reduction of cholesterol levels from 900 mg/dl to 700 mg/dl would 
be of any benefit to the patient particularly when the remaining level would still be so 
high. Dr. Wilson stressed that the therapy is not going to be a cure. But pharmacology 
and plasmapheresis, the currently available treatments for FH, only accomplish a 
transient decrease that eventually goes back to baseline. The hope is that the proposed 
therapy will diminish the baseline and allow the patients to better participate in the 
other therapies. The problem with drug treatment in the receptor-negative patients is 
that the pharmacology is based on up-regulating the LDL receptor. These homozygous 
patients do not have receptor, but gene therapy could give them a receptor level of 
approximately 5 %. 
Dr. Gellert asked Dr. Wilson to comment on the issue of telling patients that they should 
not withdraw after resection and before reinfusion. Dr. Gellert asked Dr. Wilson if he 
was comfortable with withdrawing that as part of the design. Dr. Wilson said a 
statement has been included indicating explicitly that the patient can withdraw at any 
time. Dr. Gellert said that there is an explicit statement that it would be critical for 
patients not to withdraw at this particular time. He said that a patient should always be 
free to withdraw regardless of the fact that they have taken the risk and are not deriving 
benefit. He asked Dr. Wilson to modify the protocol to reflect that stance. Dr. Wilson 
said he would make the changes. 
Dr. Leventhal moved to approve the protocol, for the treatment of three patients as 
requested by Dr. Wilson. Dr. Kelley seconded the motion. 
Mr. Barton moved that the treatment be restricted to adults. Dr. Leventhal refused to 
accept the amendment, because she said that the treatment should be available to 
patients on the basis of symptoms, not age. 
Mr. Barton stated concern about small children not being of age to consent to these 
experiments where risk is involved. There is an adequate adult patient population 
available for the initial three treatments in which expected and unexpected risks can be 
assessed. After the first three patients, the age limit could be removed. 
Recombinant DNA Research, Volume 15 
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