Human Gene Therapy Subcommittee - July 29-30, 1991 
I. CALL TO ORDER 
Dr. Walters (Chair) called the meeting to order. He presented a summary of the 
human gene therapy /transfer protocols that had been previously reviewed by the 
HGTS. There have been a total of ten protocols, eight gene marking studies and two 
gene therapy protocols. The HGTS forwarded nine of the ten protocols to the RAC 
for review. Tlie RAC recommended approval of eight of these studies to the NIH 
Director, these eight protocols were approved, published in the Federal Register as 
major actions, and appended to the NIH Guidelines for Research Involving Recombinant 
DNA Molecules. Of the eight NIH-approved protocols, only sk have been reviewed 
and approved by the Food and Drug Administration (FDA). On today's agenda, five 
new gene therapy protocols are to be reviewed. 
II. PROPOSED ADDITION TO APPENDIX D OF THE NIH GUIDELINES 
REGARDING A GENE THERAPY PROTOCOL ENTITLED: GENE THERAPY OF 
FAMILIAL HYPERCHOLESTEROLEMIA 
Dr. Erickson described this protocol as a treatment for severe low density lipoprotein 
(LDL) receptor deficiency or Familial Hypercholesterolemia (FH), by autologous 
reinfusion of hepatocytes that have been transduced with the LDL receptor gene. The 
investigators employed a relevant animal model, the Watanabe rabbit, to generate 
preliminary data that suggests this approach may be effective in the treatment of this 
disorder. He asked the investigators to address whether autologous infusion of 
hepatocytes in humans would have the same success rate that has been seen in rabbits. 
There is a considerable amount of experimental data in mice and in rabbits. Minimal 
data are available from rats, and only one baboon study has been performed. 
However, one cannot assume that this approach will work as well in humans as it has 
in the animal models. The choice of the portal vein as the site of injection may also be 
problematic. 
Dr. Erickson said that patient selection is a point of concern. He explained that the 
choice is between treating receptor-negative children with life expectancies of 
approximately 10 years or treating adults that have low levels of receptor, longer life 
expectancies, and alternative therapies available to them. The investigators could start 
with the adult patients. However, the Watanabe rabbit model suggests that therapy 
would be more effective in children. This is an excellent protocol with good 
preliminary data. 
Dr. Mclvor stated that this was an excellent protocol. There are substantial preclinical 
data generated using the rabbit model, and gene transfer and expression in human 
hepatocytes has been sufficiently demonstrated. The plan is to resect a portion of the 
liver, isolate hepatocytes from that tissue, introduce the gene for the LDL receptor into 
the hepatocytes, and then to reinfuse this material into the liver through the portal 
[882] 
Recombinant DNA Research, Volume 14 
