Transatlantic research partnership has diabetes-related blindness in its sights

Research funding of €2.25m was received through the US-Ireland R&D Partnership Programme, a single-proposal, single-review mechanism, which supports tri-jurisdictional projects and which are jointly funded by the National Institutes of Health (NIH) in the USA, Science Foundation Ireland (SFI) and HSC R&D in Northern Ireland.

The five year programme will commence in April 2016.

Globally, 285 million individuals have diabetes mellitus, a figure expected to rise dramatically over the next 15-20 years, forecasting significant healthcare and socio-economic challenges.

One such challenge is diabetic retinopathy (DR), a widespread complication of diabetes and now the leading global cause of new blindness cases in working age adults. DR is caused by chronically elevated blood glucose levels which can severely damage the blood vessels in the retina at the back of the eye. Existing DR therapies, however, have significant limitations, such as laser photocoagulation which can reduce visual performance, or anti-VEGF drugs which only have a 30% success rate amongst patients.

A new US-Ireland R&D partnership will bring together a unique team of scientists and clinicians led by Professor Bala Ambati (University of Utah Moran Eye Centre), Dr Phil Cummins and Dr Niall Barron (Dublin City University School of Biotechnology), and Dr Tim Curtis, Professor Alan Stitt and Dr Reinhold Medina (Queen’s University Belfast Centre for Experimental Medicine), to develop an improved gene therapy based on a modified form of human angiopoietin-1 (COMP-Ang-1) to potentially reverse blood vessel damage during diabetes and ultimately restore visual function.

The research team will develop an improved gene delivery approach based on the well-established adeno-associated virus (AAV) system to improve delivery of the drug directly to the retina. It will also investigate how the drug can prevent inflammation and improve the function of cells within the retina. Finally, it will investigate the ability of the drug to mobilise stem cells to facilitate the reversal and repair of diabetic damage to the retina.

The DCU team will focus on how to optimise and improve the delivery of COMP-Ang-1 into retinal cells by manipulating the AAV delivery system. Dr Phil Cummins explained,

“The DCU team are established experts in the fields of cell engineering and vascular biology, and are delighted to be part of this tripartite consortium addressing a major global health challenge. Up to 12 different AAV serotypes have been used for gene delivery studies. Our aim is to identify, manipulate and utilise AAV serotypes that will significantly improve COMP-Ang-1 delivery into retinal cells in order to combat diabetic retinopathy. ”

The Queen’s University partners will model diabetes in stem cells and test the effect of the drug. Dr Tim Curtis said,

“During diabetes, the ability of circulating stem cells to repair damaged blood vessels in the retina is impaired. Our aim is to examine whether treatment of these cells with COMP-Ang-1 is capable of preventing or reversing diabetic retinopathy by improving vascular repair and blood flow in the retina.”

At the University of Utah, researchers will ascertain how the drug prevents inflammation in DR using the smallest possible drug dose to achieve optimal long-term effect while minimising side-effects of toxicity. Prof Bala Ambati explained,

“We will explore whether combining stem cells with COMP-Ang1 treatment can reverse blood vessel damage and protect nerve cells in advanced diabetic retinopathy associated with Type 1 diabetes. This will establish the concept of treating retinal damage in diabetic retinopathy, the leading cause of blindness in the working-age population around the world.”

About US-Ireland R&D Partnership Programme

The US-Ireland Research and Development Partnership, launched in July 2006, is a unique initiative involving funding agencies across three jurisdictions: United States of America (USA), Republic of Ireland (RoI) and Northern Ireland (NI). Under the US-Ireland R&D Partnership programme, a ‘single-proposal, single-review’ mechanism is facilitated by the National Science Foundation (NSF) and National Institutes of Health (NIH) who accept submissions from tri-jurisdictional (USA, NI and ROI) teams to a number of their existing funding programmes. All proposals submitted under the auspices of the Partnership must have significant research involvement from researchers in all three jurisdictions. As part of this funding process, the governments and relevant research funding agencies within the Partnership contribute to the research costs of researchers based in their jurisdictions.