II. Non-technical Abstract Non-Technical Abstract 
The purpose of this clinical investigation is to determine if gene therapy can be used to cause 
! the development of new blood vessels in legs with blocked arteries, and to further determine if the 
additional blood flow which is provided by such new blood vessels will be sufficient to eliminate leg pain 
present at rest ("rest pain") and/or heal ulcers in the feet and legs. 
While angioplasty techniques and/or surgery may often increase blood flow in patients with 
blocked arteries sufficient to relieve rest pain and/or heal ulcers, the blockages may in some cases be too 
extensive to permit either of these therapies. No medications are currently available that are likely to 
accomplish relief from rest pain or heal ulcers. Accordingly, we are investigating a new strategy, gene 
therapy, which has not been used previously for the treatment of lower extremity arterial insufficiency. 
This therapy has been tested thus far in laboratory animals; the experiments suggest that if one performs 
surgery on the animal (rabbit) to create blockages in the leg arteries, one can use gene therapy to grow new 
blood vessels around the blockages; this treatment is termed "therapeutic angiogenesis." 
The treatment will involve using a catheter - similar to catheters which are used to perform 
balloon angioplasty - to deliver DNA, or genetic material, to one of the arteries which is still open in the 
diseased leg. The DNA is delivered to the wall of the artery from the balloon of the catheter when the 
balloon is inflated. Once in the arterial wall, the DNA then directs the cells of the artery wall to make a 
certain protein, in this case a protein called vascular endothelial growth factor (VEGF). VEGF is a protein 
which has been shown to cause new blood vessels to grow under a variety of conditions, including the 
above-described rabbit experiments in which both the protein and the gene for the protein caused new 
blood vessels to develop in the leg with arterial blockages. 
We are thus investigating the possibilty that by using a catheter to transfer the gene for VEGF 
to the arterial circulation of a leg with blocked arteries , new blood vessels will develop that will reduce 
pain in the leg and/or heal an ulcer. 
Recombinant DNA Research, Volume 20 
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