Preventing neointimal hyperplasia in arteriovenous fistulas and grafts through viral-mediated TIMP-3 overexpression (PREVENT)

Arteriovenous fistulas (AVF) or grafts (AVG) are the cannulation points for haemodialysis machine connections in patients with end-stage renal disease. The venous lumen of these vascular access sites narrows through intimal hyperplasia, thereby reducing blood flow and leading to failure of the AVG or AVF. Although stenosis caused by intimal hyperplasia can be easily treated by percutaneous balloon angioplasty, the underlying haemodynamic disturbances remain and stenosis tends to recur within months. This project will assess whether a gene therapy approach that overexpresses human TIMP-3 is a novel and clinically relevant approach to treating AVF and AVG to prevent neointimal hyperplasia. This is a new collaboration between partners Maastricht University, the University of Glasgow and Batavia Biosciences Bv.

If successful, this project will lead to subsequent in vivo experiments in pigs to select the most effective viral vector to use in the next clinical phase. Eventually, viral TIMP-3 overexpression may become a gene therapy to complement AVF and AVG surgery which would have a major benefit to society for this unmet clinical need.

The consortium will develop a biobank of tissues and create a novel virus expressing the therapeutic gene. They will assess its expression and function using cell culture models that mimic the disease processes.

By the end of the project, they will know whether the new gene therapy is worthy of developing into a clinical therapy and moving to the next stage of development.