careful pretreatment evaluation that may include cardiac catheterization. Patients will be 
excluded from the protocol if 1) cardiac evaluation indicates a relatively good prognosis, 2) 
operative risks are too great, and 3) a second dyslipidemia or concurrent hepatobiliary disease 
is present. Children and adults will be considered potential candidates. 
The important steps in the evaluation and treatment of the patients are summarized in 
Table 5. The indicated time frame is based on defining Day 0 as the time of liver resection. 
Table 5 
Events 
Time 
1 . Begin diet, withdraw drugs, receive last plasma exchange (-) 6 weeks 
2. Admit to CRC for 2-3 days (-) 4 weeks 
Initial evaluation will include physical exam, history, 
blood work, echo with doppler, and possibly ETT or 
cardiac catheterization 
3. Biweekly blood draws to establish metabolic baselines 
(-) 4 weeks to (-) 1 week 
4 . Admit to CRC for gene therapy 
(-) day 7 to (-) day 10 
A. 
Preoperative evaluation 
(-) day 7 to (-) day 1 
B. 
Liver resection 
day 0 
C. 
Hepatocyte infusion 
(+) day 3 
D. 
Post operative evaluation 
(+) day 3 to (+) day 10 
Post treatment evaluations as outpatient 
A. 
Biweekly blood work x 4 weeks 
(+) day 10 to (+) week 4 
B. 
Weekly blood work x 6 months 
(+) week 4 to (+) month 
C. 
Resume pretreatment therapies 
(+) week 6 
D. 
Percutaneous liver biopsy 
(+) month 3 
The patient will undergo preliminary evaluation during a 6 week period prior to the 
treatment to assess their suitability for the procedure and establish metabolic baselines. The 
patient will then be admitted to the hospital for the gene therapy which will include the 
following procedures. The patient will be subjected to partial hepatectomy to remove the left 
lateral segment of the liver. This biopsy represents approximately 20% of the total liver by 
mass and weighs approximately 70 gm if removed from a 4 year old. Approximately 5 x 10 9 
hepatocytes will be isolated from the biopsy and the cells will be plated in primary culture. 
Recombinant retroviruses capable of transducing the gene for human LDL receptor will be 
exposed to the cells for a 12-16 hour period approximately 48 hours after the initial plating. 
Following exposure to virus (60 hours after partial hepatectomy) the cells will be harvested, 
washed, and infused into the portal circulation of the patient via a percutaneous catheter 
inserted at the time of the partial hepatectomy. 
The patient will be analyzed for engraftment of functionally corrected hepatocytes at 
several levels. A series of measurements will be performed to assess the effect of hepatocyte 
engraftment on cholesterol metabolism in vivo. In addition, liver tissue will be harvested 3 
months after the gene therapy by percutaneous liver biopsy and will be analyzed for the 
Recombinant DNA Research, Volume 15 
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