VEGF111, a novel naturally occurring isoform of human VEGF-A, was recently cloned. VEGF111 is active in terms of activation of VEGF receptors, induction of endothelial cells multiplication and stimulation of vascularisation in vitro and in vivo. As r

A newly described human VEGF-A isoform (VEGF111) has been cloned from UV-B treated cells. The protein lacks the sequence encoded by exon 5, which contains the main site of cleavage by plasmin. Recombinant VEGF111 retains full biological activity and is resistant to degradation by plasmin and wound fluid exudates collected from chronic ulcers. In nude mice, the effect of local expression of various isoforms of VEGF-A was investigated by subcutaneous injection of HEK293 cells expressing VEGF111, VEGF121 or VEGF165. Expression of the three isoforms resulted in an intense angiogenesis. Of particular interest, VEGF111 was able to induce a dense network of functional capillaries in a much larger area than VEGF165 and VEGF121. It also resulted in enlargement of the diameter of the existing vasculature at distance of the site of injection of the cells.

In the past, the use of VEGF has been investigated for the treatment of severe burns and chronic wounds as venous, pressure and diabetic ulcers. Increased proteolytic degradation of VEGF in chronic wounds is regarded as one of the reasons of unsatisfactory results. Our data suggest that VEGF111 should allow overcoming these limitations, due to both its high resistance to proteolysis and its capability of inducing angiogenesis.

Taking advantage of the properties of VEGF-111 could also benefit to the treatment of other pathologies for which the use VEGF has already been reported (cardiovascular diseases such as angina pectoris, intermittent claudication) or is under investigation (erectile dysfunctions, amyotrophic lateral sclerosis and hair loss).

Early Stage

Patent application under prosecution WO 2007/083246A2

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