Project Summary
Tailored Gene Therapeutic Strategies for Peripheral Vascular Disease (PVD).
What is the issue for NSW?
The issue this research addresses is PVD, the prevalence of which is increasing globally with 1 in 5 Australians affected. PVD carries a poor prognosis, reduced life expectancy and risk of amputation. Of PVD patients in NSW hospitals, 34% of patients discharged experienced at least one complication while 35% of patients were re-admitted to hospital within one month of leaving hospital.
PVD requires endovascular repair (i.e. mending inside the blood vessel) with drug-coated stents or balloons or bypass grafting of narrowed arteries. However, graft failure and restenosis (i.e. renarrowing of the blood vessel) in PVD is observed in 30-40% of patients within 2 years due to re-occlusion and blood clots (thrombosis); pathologic features of failed haemodialysis arteriovenous fistulae where overall primary patency rate at two years is only 55%. Re-occlusion and thrombosis occurs because cells called smooth muscle cells (SMC) grow aggressively while endothelial cells (EC) grow poorly.
What does the research aim to do and how ?
This project aims to develop a novel cell selective gene therapeutic (YY1B) to prevent complications in PVD treatment (post-intervention restenosis, graft stenosis and fistula failure) using tailored AAV selection strategies bringing together world leaders in gene therapy, PVD and translational research.
There are four aims: first, construct and test novel viral constructs of YY1B with vascular cells and human veins; second, to investigate the protective of viral YY1B in 2 animal models of graft stenosis; third, determine the inhibitory effects of viral YY1B in a diabetic model of in-stent restenosis; and finally, to understand how YY1B works.