Angiogenesis represents an emerging therapeutic target which by 2006, is expected to command a market of $1.75 billion. A growing component of this market centers on the use of stimulators of angiogenesis for the treatment of ischemic diseases. Considerable evidence supports the use of the prototypic angiogenic growth factor, VEGF for the treatment of various related conditions including angina, myocardial infarction, stroke and peripheral artery occlusive disease (PAOD). Together, preventing the occurrence and reoccurrence of these conditions remain a pressing clinical priority. Well over 12.5 million people in the US suffer from one or more of these conditions resulting in around 1 million deaths each year and a health care expenditure of over $US100 billion each year. Thrombolytic, antithrombotic and anticoagulant treatments represent the major acute therapeutic options for the treatment of ischemic disorders (click here for "Heart/ Cardiovascular Disease 2002" an analysis of future directions in cardiovascular therapeutics). However, stimulating angiogenesis in ischemic tissue would carry significant advantages.

A number of clinical studies have demonstrated that VEGF gene therapy can be beneficial in patients with myocardial disease or PAOD. The therapeutic utility of recombinant human VEGF (rhVEGF) has now also been validated. VIVA (Vascular endothelial growth factor in Ischemia for Vascular Angiogenesis) is a double-blind, placebo-controlled trial that was designed to evaluate the safety and efficacy of intracoronary and intravenous infusions of rhVEGF. This study involved 178 patients with stable exertional angina, unsuitable for standard revascularization who received rhVEGF by intracoronary infusion for one day followed by intravenous infusions over the next 9 days. Exercise treadmill tests, angina class, and quality of life assessments were performed at 60 and 120 days later. Myocardial perfusion imaging was performed 60 days later.

This study reported that rhVEGF is safe and well tolerated and furthermore that it significantly improved angina class by day 120. There was also a trend towards improved performance on exercise treadmills and reduced angina frequency. This study paves the way for larger trial that evaluate the efficacy of rhVEGF as well as the development of similar approaches that may further optimize the use of VEGF or its mimics.

Entry date Tuesday, April 22, 2003

Adapted from Henry et al, Circulation 2003 Mar 18;107(10):1359-65- Interested in collaborating with this group? Contact LeadDiscovery or the authors direct.

Interested in collaborating with this group? Contact leaddiscovery@bioportfolio.co.uk