rAAV.MRTF-A-based vascular gene therapy in chronic hindlimb ischemia

Though narrowing or complete occlusion of a large artery is nowadays treatable by surgical or interventional means (bypasses or ballon angioplasty and stenting, respectively), smaller arteries are not amenable for these techniques. We propose a complementary treatment by growth and maturation of small vessels which are often rarefied or absent due to prolonged hypoxia and /or microvascular inflammation caused by cardiovascular risk factors (diabetes, hyperlipidemia). As an agent to regrow functional microvessel networks, we propose long expressing adeno-associated viral vectors encoding for MRTF-A, a signaling co-factor in the SRF-pathway, which promotes both: proliferation of the microvessels and their stabilisation. This agent will be tested in a pig model of femoral artery occlusion in control and diabetic/hyperlipidemic pigs. An accompanying program is studying side-effects (biodistribution and toxicology).