Recombinant DNA Advisory Committee - 12/3-4/92 
uptake and expression of the gene, and assayed for LDL receptor activity. LDL receptor 
activity was assessed by incubating the cells with fluorescent labelled LDL ligand and 
analyzing by fluorescent microscopy. A plate-to-plate variation of between 5 and 25% 
positive cells were observed. 
Visualization procedures indicated an even distribution of the infused cells into the 
intrahepatic circulation. The patient demonstrated no evidence of clotting or 
intraluminal thrombus. 
Three months following the treatment, the patient returned for clinical evaluation. 
Following a liver biopsy, the patient demonstrated no evidence of gross pathology. Her 
liver function tests were normal. Immediately following the cell infusion, the patient's 
LDL cholesterol decreased to approximately 180 milligrams per deciliter. Since the 
patient most likely had LDL receptors at this point, she was given medications to lower 
her cholesterol. Her LDL cholesterol levels continued to drop slightly; however, this 
may be due to fluctuations. The patient's HDL cholesterol level, which was originally 
very low, is increasing. The combination of increasing HDL and decreasing LDL has 
decreased her cardiac risk factor from 10 to 5. 
Dr. Wilson described numerous patients who have been evaluated. A second patient 
from Costa Rica has been identified and evaluated. Recently, 3 additional patients have 
been identified who are eligible and would likely benefit from this treatment. However, 
due to the limitation on the number of patients, he requested a minor modification to his 
previously approved protocol. This minor modification would extend the number of 
eligible patients from 3 to 5. Increasing the number of patients would allow the 
investigators to treat 2 brothers from Cyprus ages 8 and 12, who have severe coronary 
artery disease and a 7 year old girl from the United States whose sister died at age 3 of 
severe coronary artery disease. 
Committee Motion 
A motion was made by Dr. Leventhal and seconded by Ms. Buc to extend the patient 
enrollment for this protocol from 3 to 5 patients. The motion to approve the minor 
modification was approved by a vote of 16 in favor, 0 opposed, and no abstentions. 
VII. ADDITION TO APPENDIX D OF THE NIH GUIDELINES REGARDING A HUMAN 
GENE THERAPY PROTOCOL ENTITLED: GENE THERAPY OF CYSTIC FIBROSIS 
LUNG DISEASES USING El DELETED ADENOVIRUSES: A PHASE I TRIAL /DR. 
WILSON 
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Recombinant DNA Research, Volume 16 
