Recombinant DNA Advisory Committee - 10/7-8/91 
it will be decided if the patient would be a possible candidate. The patient would be 
brought to the University of Michigan four to six weeks before the procedure for a two 
to three day visit in the University Clinical Research Center at the Center's expense. 
The patient will be informed about the procedure. Dr. Wilson said he will personally 
talk to patients about the protocol. There will be a non-invasive evaluation of their 
eligibility; and if selected, therapy will be offered. After therapy, the patient will be 
discharged within ten days, and there will be subsequent follow-up with respect to the 
metabolic analysis. 
Dr. Wilson said that experiments had been also performed in one baboon. The goals of 
the baboon experiment were to demonstrate the feasibility of the surgical and logistic 
issues of the procedure. They also wanted to look at issues of short-term toxicity, 
specifically issues that relate to harvesting and growing the cells as well as any 
complications of the reinfusion and of the catheter insertion. The therapy was 
administered, and the animal subjected to a laparotomy. The animal was checked for 
patency of the portal circulation, and a liver biopsy was performed. In the long-term 
follow-up, the animal was clinically normal, and the chemistry and hematology were 
within normal limits. 
Dr. Wilson addressed patient selection issues. First, the receptor status is checked. If 
the patients are receptor-negative, they have a poor prognosis. Whereas if they are 
receptor-defective, some patients have a poor prognosis; but it is difficult to stratify that 
group. Thus, their disease status will be carefully evaluated. The patients will be 
evaluated by history and physical exam, echo with Doppler, and an exercise test to 
identify those who have absolute contraindications. At that point if they have acceptable 
risks, they would be considered as candidates for therapy. 
Dr. Leventhal asked if there is a reasonable alternative therapy for this group of 
patients. Dr. Wilson said most of these patients are followed by a lipid center and are 
being managed either by plasmapheresis, drugs, or both. In terms of his own clinical 
interest, he would like to have the opportunity to manage some homozygotes by 
whatever means appropriate. Treatment has to be individualized; there is no standard 
therapy because nothing seems to work. If and when a liver transplant becomes 
indicated, it would be offered to the patients. 
Mr. Capron said there is a potential problem whenever rare diseases are studied, and 
people are transported to a center for only that purpose. He asked what could be done 
to have more of the education and the real decision-making, including Dr. Wilson's 
conversations with the patient's, occur in the patient's local clinical center before coming 
to the University of Michigan. Dr. Wilson replied it is possible, given the quality of 
some of the local clinicians, but it is equally possible that the patient may gain additional 
insight from in conversations with the investigators at their first meeting in Michigan. 
Recombinant DNA Research, Volume 15 
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