Human Gene Therapy Subcommittee - July 29-30, 1991 
will be dealt with should they occur. A stopping rule should be imposed to prevent 
reintroduction of transduced cells into patients if problems in quality control are 
encountered. Dr. Erickson accepted the amendments to his motion. 
Dr. Walters restated the motion to approve the protocol with the stipulations that: (1) 
the protocol is to be limited to receptor-negative patients, (2) the consent form should 
be separated and subsequently reviewed by select RAC members, (3) additional 
information must be provided on the vector construction and quality control of the 
virus, the packaging cell line, and the transduction process, and (4) a stopping rule 
should be included. 
Dr. Epstein disagreed with the stipulation which limited the treatment to receptor- 
negative patients. The short-term goal of this experiment is the reduction of LDL 
cholesterol, and this is independent of the age of the patient. Because the receptor- 
deficient patients have some endogenous receptor activity, they have lower cholesterol 
levels than the receptor-negative patients. Given the incremental increase in the level 
of receptor, these patients may do better over time. Since the patient population is 
rare, an arbitrary restriction may be more severe than necessary. 
Dr. Erickson said he would not remove the stipulation limiting the treatment to 
receptor-negative patients. Dr. Epstein moved that the motion be amended to have 
this stipulation removed. Mr. Capron seconded the motion. 
Dr. H. Miller noted that the investigators' intention was to include patients who were 
severely affected, even if they did not meet the strict definition of receptor-negative. 
He urged that the protocol be left open to receptor-deficient patients. 
Dr. Parkman noted that the 2% receptor level cut-off used to define the receptor- 
negative patients was arbitrary. Actually it is a continuum, and patients in the 
advanced stages of the disease will be treated. 
Mr. Capron favored Dr. Epstein's proposal. On the therapeutic level, one hypothesis is 
that the treatment is more likely to clinically benefit the receptor-deficient patients 
than the receptor-negative patients. The implication is that if the treatment is limited 
to receptor-negative patients, it will only be children who are treated. He stressed that 
there are patients old enough to consent who would qualify for this protocol. 
Dr. Erickson said the chance of determining if the treatment has had a significant 
effect is much greater in the receptor-negative patients who have not already had many 
of the clinical manifestations of the disease. 
Dr. Leventhal said it would be wrong for the subcommittee to limit the patients who 
could go on this study. It is a rare disease; and if patient selection is limited too 
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