A Preclinical Trial of Therapeutic Angiogenesis Plus Angioplasty and Stenting for Renal Vascular Disease

Abstract Chronic kidney disease CKD is a progressive disorder affecting almost of the general population and this disease has shown a relentless growth over the past decades Patients with CKD have higher rates of hospitalization greater mortality shorter life expectancy and their healthcare costs are up to times more expensive than non CKD patients Thus treatments to slow halt or reverse the progression of CKD could have a significant financial and clinical impact Chronic renal vascular disease RVD often associated with renal artery stenosis can deteriorate renal function and lead to CKD and end stage renal disease in up to of patients Despite the availability of treatments for RVD including drugs and percutaneous transluminal renal angioplasty PTRA renal function does not improve or even deteriorates in over half of the patients undergoing these treatments Leflore Technologies has developed a biopolymer stabilized form of vascular endothelial growth factor VEGF with high renal binding This Phase I STTR will test the feasibility of PTRA and stenting plus therapeutic renal angiogenesis with our biopolymer stabilized VEGF in a preclinical trial using a swine model of chronic RVD Recently we have demonstrated that our biopolymer fusion greatly stabilizes the growth factor from degradation and plasma or tissue clearance and mediates deposition in the kidney following intrarenal administration Furthermore we have compelling preliminary evidence that our biopolymer delivered VEGF is highly efficacious for restoring renal function in the swine model The proposed Phase I studies will carry out preclinical efficacy and safety trials of PTRA and stenting in combination with our biopolymer delivered VEGF compared to PTRA and stenting alone or PTRA and stenting with standard of care pharmacotherapy These studies will examine the efficacy of this strategy relative to current clinical standard of care the efficacy of this strategy at early middle and late stage RVD and the long term efficacy and safety of the intervention Future Phase II studies will involve good manufacturing and practice GMP production of our recombinant biological agent chemistry manufacturing and controls testing and expanded preclinical IND enabling toxicology Narrative Chronic renovascular disease can deteriorate renal function leading to the need for dialysis and it increases the risk of heart attacks strokes and death Current treatment for renovascular disease involving renal angioplasty and stenting combined with pharmacotherapy with anti angiotensin agents and statins are ineffective in up to half of the patients The goal of this Phase I STTR is to test the efficacy and safety of a novel biopolymer stabilized vascular endothelial growth factor to recover the kidney after renal angioplasty using a swine model of chronic renal vascular disease that is very similar to human disease