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Biotech / Medical : Corgentech (CGTK) -- Ignore unavailable to you. Want to Upgrade?

To: tuck who wrote (16)	11/18/2004 7:55:27 PM
From: Archie Meeties	Read Replies (2) \| Respond to of 39

We're talking about three different procedures, two of which CGTK is involved with. 1. CABG 2. Peripheral bypass 3. AV Grafts for Hemodialysis Shared characteristics; The use of a graft designed for low pressure flow in a high pressure system. That is, using a vein where nature intended an artery. The development of intimal hyperplasia as a response to being subject to high pressure. The subsequent development of occlusion, either from the hyperplasia itself, or more likely from the risk it confers for atheromatous plaques. Important Difference; In 3, the purpose is to facilitate hemodialysis. This entails creating a high pressure system (so that the blood flows freely into the hemodialysis machine) and joining it to the venous system. In bypass and cabg, your graft is merely a bridge from artery to artery. "I don't understand the market; are shunts preferable to grafts or fistulae (some patients not suited for one or the other; infection; or?)? In other words, if one solved the problem in grafts, would anybody bother with shunts anymore?" Synthetic grafts (gortex, etc) are second best to veins. They are used only when venous quality is poor to begin with. I brought up the hemodialysis idea because AV grafts are notorious sob's (or a vascular surgeons bread and butter, depending on how you look at it). If a vein could be transfected in vivo, that would be huge. In the current procedure, the cephalic vein is anastamosed to the radial artery. The vein is just mobilized a bit - it never leaves the body.

To: tuck who wrote (16)	11/18/2004 8:07:03 PM
From: SnowShredder	Respond to of 39

Hey Tuck, I can find precious little info about the methodology being used in the trial (I imagine their device using a process of filling up a water balloon with tiny holes in it, where the graft is a balloon with the decoy being in the water...bwdik?) I found a couple things... Best of Luck, SS svmb.org >>>> clinicalcardiology.org PREVENT II (Genetic Manipulation of Vein Graft Remodeling with E2F Decoy® Therapy in CABG patients) Presenter: Eberhard Grube, M.D., at the American Heart Association Scientific Sessions 2001, Anaheim, California. Background: An estimated 30 to 50% of bypass leg and coronary bypass grafts eventually fail. E2F Decoy® (Corgentech, Inc., Palo Alto, Calif.) is an oligonucleotide, or short strand DNA, that binds to and inactivates the pivotal cell-cycle transcription factor E2F. E2F is responsible for activating a dozen or more genes that must be turned on during vascular cell growth and multiplication. Its blockade prevents the proliferation of these abnormal cells (neointimal hyperplasia) that eventually result in atherosclerotic lesions. Objective: PREVENT II tested the hypothesis that ex vivo, intra-operative treatment of vein grafts with E2F Decoy inhibits graft intimal disease and reduces rates of critical graft stenosis and failure. Methodology: After being harvested in the usual manner from the leg or arm, the vein grafts are bathed for about 10 minutes in the E2F Decoy solution outside the body in a proprietary pressure-mediated device. The surgeon then inserts the E2F Decoy-treated graft into the patient. Two hundred CABG patients (mean age 66.5 years, 84% male, 100% Caucasian) who received at least two coronary grafts each were randomized in double-blinded fashion to placebo or E2F Decoy. Primary endpoints in this safety and feasibility trial were toxicity and side effects, graft occlusion, or critical graft stenosis (lumen reduced >75%). Angiography and ultrasound were performed at 12 months. Results: At follow-up in the placebo group, 38.7% of 127 grafts had >75% stenosis. Among 172 grafts treated with E2F Decoy, the rate was 27.3%, a 30% relative reduction (p = 0.03). With grafts with initial flow <25 ml/min excluded, rates were 30.3% for placebo and 18.3% for E2F Decoy (40% reduction, p = 0.03). Major clinical events occurred in 16% of placebo-treated and 12% of E2F Decoy-treated patients, respectively. Among 108 cases with IVUS evaluation at one year, the vascular wall volume/index decrease was highly significant in the E2F Decoy group. The drug was safe and well tolerated. Conclusion: In this first, randomized controlled trial of genetic suppression via transcription factor inhibition in CABG patients, vein graft stenoses and vascular wall volume/index were significantly decreased.