Recombinant DNA Advisory Committee- 9/12-13/94 
on gene therapy for arterial restenosis. 
Mr. Capron pointed out that the statement in Paragraph E about withdrawal from the 
study in the Informed Consent document, is repeated in Paragraph G regarding long-term 
follow-up. He asked about the reason for the repetitive statements. Paragraph F on 
angioplasty intervention was confusing. 
Dr. Isner said that repetitive statement resulted from adding additional statements to the 
standard Informed Consent document of the hospital. He was willing to revise it. 
Regarding the angioplasty statement, Dr. Isner said it is a statement suggested by his IRB 
so that patients are not confused when they consent to a standard angioplasty procedure. 
He agreed to revise the statement to avoid ambiguity. 
Responding to Dr. Straus’s question on retinopathy, Dr. Isner said that retina was not 
examined in the rabbit experiment. In another animal experiment with 22 rabbits, no 
neovascularization was observed in many different organs after gene transfer or 
administration of recombinant VEGF. He appreciated Dr. Straus’s concern, and 
funduscopic examination will be performed on the subjects before and after gene transfer. 
This risk in Type II diabetics is considered to be very low according to the advice received 
from ophthalmologic and endocrinologic consultants. It is unreasonable to exclude 
patients who have serious risk of limb loss. 
Dr. Straus suggested a complete ophthalmologic examination before and after gene 
transfer. The issue of retina involvement should be addressed in the future animal 
studies. Dr. Motulsky said funduscopic photography of each patient will be useful. Dr. 
Isner agreed to the suggestions. 
Dr. Parkman asked if observation has been carried beyond 30 days in animals for 
collateral neovascularization. Dr. Isner said his colleagues have observed the animals for 
90 days, and there is no further vessel growth after 30 days. 
Dr. Isner used a slide to show data on the time course of transgene expression. 
Expression peaks on day 14 and day 20, declines on day 21, and disappears by day 30. 
Responding to Dr. Saha’s question on comparison of the present study to that of Dr. 
Nabel’s Science article, Dr. Isner said that the two approaches are very different 
applications of gene therapy for vascular disease. Dr. Nabel’s study involved application 
of an adenovirus encoding the Herpes simplex thymidine kinase gene to artery endothelium 
after balloon angioplasty to prevent restenosis. It is a very different approach from the 
present study to stimulate new vessel growth. 
Regarding the suggestion of pain scale, Dr. Isner said that there is a pain scale developed 
by the European Consensus Document, and it can be used as a valid endpoint to measure 
the effects of pain medication. He will incorporate that pain scale in the protocol. He 
will require the subjects to keep a diary about pain and medication, as suggested by Dr. 
Parkman. 
[70] 
Recombinant DNA Research, Volume 20 
