Recombinant DNA Advisory Committee - 12/3-4/92 
assay be performed? Dr. Crystal stated that 10 6 cells will be used with a MOI of 1000. 
Dr. D. Miller explained that the assay described by Dr. Crystal reflects 10 9 particles. 
Since some patients will receive 10 11 particles, how will less than 1 replication-competent 
particle in 10 be determined? Dr. Crystal agreed that this determination would have to 
be made on a cell line, not fresh human epithelial cells. Dr. Ginsberg noted that there 
are existing cell lines that are actually more sensitive that human epithelial cells. 
Committee Motion 
A motion was made by Dr. Parkman and seconded by Dr. Schaechter that Dr. Crystal's 
protocol be approved with following stipulations: (1) the title of the protocol and 
informed consent document should be changed as suggested by Dr. Walters, (2) the 
informed consent document should include a statement that there is no expected long- 
term clinical benefit from this treatment, and this statement should be included at the 
beginning of the benefit section, (3) individuals will not be excluded from participation in 
this protocol based on their fertility status, and (4) demonstrate that there is less than 1 
replication-competent adenovirus helper particle in 20 ml of the highest vector 
concentration. The motion to approve the protocol with the aforementioned stipulations 
was approved by a vote of 17 in favor, 0 opposed, and no abstentions. 
VI. MINOR MODIFICATION AND SUMMARY PRESENTATION OF THE PROTOCOL 
ENTITLED: EX VIVO GENE THERAPY OF FAMILIAL 
HYPERCHOLESTEROLEMIA t /DR. WILSON 
Presentation— Dr. Wilson 
Dr. Murray called on Dr. James Wilson of the University of Michigan Medical Center, 
Ann Arbor, Michigan, to present an update on his approved human gene therapy 
protocol. Dr. Wilson explained that familial hypercholesterolemia (FH) is an autosomal 
dominant disease in which patients inherit two defective genes. One of these genes is 
the gene that encodes for the low-density lipoprotein (LDL) receptor; therefore, patients 
are either homozygous or compound heterozygotes. The function of the LDL receptor is 
to metabolize LDL. A deficiency in this gene, results in the accumulation of LDL 
cholesterol levels between 500 and 1,000 milligrams per deciliter. For reasons that are 
unclear, FH patients exhibit diminished levels of high-density lipoprotein (HDL). These 
individuals have elevated LDL cholesterol levels from birth and eventually develop 
xanthomas and premature coronary artery disease. Patients who are completely void of 
the LDL receptor are called receptor negatives. This population has an average survival 
of approximately 10 years of age due to the sequelae of coronary artery disease. Patients 
who possess residual receptor function survive into their 20s. 
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