VEGF shows promise in speeding wound healing

New London, N.H. - Vascular endothelial growth factor (VEGF) appears useful as an agonist in accelerating wound healing, according to a leading pharmaceutical company executive.

"VEGF is an important signaling protein that's involved in a wide variety of biological systems," says Charles P. Semba, M.D., F.A.C.R., group director, vascular, neurology and ophthalmology, Genentech. "This particular protein was discovered by one of our scientists, Napoleone Ferrara, M.D.(Genentech fellow, molecular oncology), who isolated and cloned VEGF and led us down the path in the arena of angiogenesis and subsequent anti-angiogenesis research."

Dr. Ferrara's work provided a basis for a major breakthrough in cancer research - the development of an antibody against VEGF in the treatment of lung and colorectal cancer (Avastin, bevacizumab, Genentech), Dr. Semba says. Presently, this drug has Food and Drug Administration approval for treating metastatic colorectal cancer.

VEGF

As for VEGF itself, he reports that Genentech already has studied this molecule in the clinic, particularly in the arena of cardiac disease, focusing on patients with severe blood vessel damage who were not candidates for traditional percutaneous therapies or open-heart surgery.

"The phase 2 trial for coronary artery disease did not achieve its primary endpoint, which was exercise tolerance compared to placebo (Henry TD et al. Circulation. 2003;107:1359-1365)," Dr. Semba says.

Animal studies

In the search for other uses for VEGF, "Further animal experiments led us to the idea that it might be a useful agonist in accelerating the rate of wound healing, particularly for diabetic patients," he tells Dermatology Times.

In preclinical models, Dr. Semba says, "We looked at this (therapy) in both diabetic and non-diabetic animal models. One of the compelling factors we know in humans is that diabetics don't produce VEGF in normal stress situations as do non-diabetics. Perhaps this is one of the reasons why diabetics get such a poor wound-healing response. It's clear from basic science that to get adequate healing of tissue, one needs a good oxygen supply, hence a good vascular supply.

"Our premise, which was confirmed in animal models, is that topically-applied VEGF results in a robust development of vascular tissue in the wound bed and can accelerate the rate of wound healing relative to placebo treatment (Daugherty A. "Clinical Development of VEGF for Healing Diabetic Foot Ulcers." Presented at the Gordon Research Conference "Tissue Repair and Regeneration," Colby-Sawyer College, New London, N.H., June 19-24, 2005)."

Potent pathway

Over the past couple years, he says, "We have embarked upon a developmental initiative looking at topically applied VEGF for chronic refractory diabetic foot ulcers, which are among the leading risk factors for limb loss in diabetic patients worldwide."

Currently, Dr. Semba says one agent is approved for wound healing in diabetics - Regranex (becaplermin, Ortho-McNeil), a recombinant platelet-derived growth factor.

"We believe that the VEGF biology provides a far more potent pathway to accelerate wound healing. Subsequently, late last year we completed a preliminary phase 1 program to examine the safety of topically applied VEGF in patients with diabetic wounds. We will be embarking upon a more robust efficacy trial probably in the first half of 2006," he says.