Recombinant DMA Advisory Committee- 9/12-13/94 
the assay systems that are currently in use? Unfortunately, Dr. Temin has died since he 
submitted his letter, and there was no opportunity to involve him in further discussion. 
There was background information in the meeting materials, and the subject has been 
informally discussed and recorded in the minutes of June 9-10, 1994, RAC meeting. The 
conclusion of the discussion is as follows: The assays which are currently in place and 
accepted by both the RAC and FDA for detection of RCR are adequate, irrespective of 
the mechanisms by which these recombinant RCR are generated. In view of this, the 
consensus of the Working Group members was that further discussions of this subject was 
not necessary. 
Dr. Walters noted no further comment from participants of this telephone conference. 
XVII. ADDITION TO APPENDIX D OF THE NIH GUIDELINES REGARDING A HUMAN 
GENE TRANSFER PROTOCOL ENTITLED: ARTERIAL GENE TRANSFER FOR 
THERAPEUTIC ANGIOGENESIS IN PATIENTS WITH PERIPHERAL ARTERY 
DISEASE/DRS. ISNER AND WALSH 
Review-Dr. Parkman 
Dr. Walters called on Dr. Parkman to present his primary review of the protocol 
submitted by Drs. Jeffrey M. Isner and Kenneth Walsh of St. Elizabeth’s Medical Center, 
Tufts University, Boston, Massachusetts. Dr. Parkman said that this protocol is exciting 
because it deals with the very common disease of atherosclerosis. Instead of focusing on 
the heart, it is directed toward disease of the peripheral arteries. Patients with peripheral 
artery disease (PAD) have pain upon walking due to compromised blood flow to their 
muscles, particularly in their lower extremities. When the blood flow is severely 
compromised, they begin to have pain at rest and develop skin ulcers. The basis for the 
decreased blood supply is the presence of atherosclerotic plaques in their arteries. No 
drugs are now available that significantly reduce the symptomatology of patients who have 
muscle pain at rest. If the PAD becomes severe enough, patients may have portions of 
their extremities amputated. Such amputation, however, does not result in long-term 
clinical stabilization. 
The investigators propose to test a new therapy in patients with PAD. This therapy is 
based upon the observation of Dr. Judah Folkman about 20 years ago that angiogenic 
growth factors are able to stimulate the production of new blood vessels. A series of 
angiogenic growth factors have been identified. The investigators propose to use a factor 
termed vascular endothelial growth factor (VEGF) which was initially isolated as a 
heparin binding factor secreted by bovine pituitary cells. It has been shown that VEGF 
stimulates angiogenesis in vivo in rats and rabbits. The investigators have performed a 
preclinical study in rabbits who have had ischemic injury induced by ligation of iliac 
arteries. The VEGF-cDNA is expressed in a plasmid DNA vector under the control of a 
CMV promoter. The plasmid DNA was introduced by an arterial catheter into the iliac 
artery. The cardiac balloon was expanded resulting in the transduction of a small 
percentage of the arterial cells. The treated animals had significantly increased collateral 
vessel growth. The use of the arterial catheters is based upon pre-clinical studies in which 
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Recombinant DNA Research, Volume 20 
