The VISICORT consortium partners met in Edinburgh, UK on Thursday, April 27th and Friday, April 28th to review progress towards the project’s major goals following three years of collaborative research. The meeting was jointly hosted at Nine, Edinburgh BioQuarter by VISICORT partners Fios Genomics Ltd. and University of Edinburgh’s SynthSys Laboratory and was attended by 25 team members from 10 partner sites.
The group was also joined by Scientific Advisory Group member, Prof. John Forrester who is Cockburn Professor of Ophthalmology University of Aberdeen and is an internationally recognised leader in immune-mediated eye disease and corneal transplantation.
The meeting focused on the consortium’s progress and future plans in its two main research activities:
Biological profiling of immune complications in corneal transplantation
Over the past three years VISICORT has successfully developed a multi-site clinical research network involving five centres of excellence for corneal transplantation (Aarhus, Berlin, Bristol, Dublin and Nantes); a central logistics and sample collection facility (Biostór Ireland, Ltd.) and specialised profiling technology / bioinformatics laboratories (Edinburgh and Nantes). To date, this network has enrolled almost 1000 corneal transplant recipients and control patients into three separate observational studies which uniquely link their biological profiles with current and future transplant outcomes.
During the first year of the project, a specially-designed secure database – VISICORT Information Management System (VIMS) – was developed by team members at Biostór Ireland Ltd. and Aarhus University Hospital in collaboration with Belfast-based company PathXL (now part of Philips Digital Pathology Solutions). VIMS has uniquely facilitated the flow of samples and linked clinical information across project sites while ensuring the highest level of data protection for study participants. This has allowed us to reach an exciting milestone in the project at which gene expression, protein abundance and blood immune cell profiles have been generated for a large number of European corneal transplant recipients and are now being linked to complications such as acute and chronic rejection.
Over the next year, much of this profiling information will be analysed in detail to reveal new details about the immunological processes that drive transplant rejection and to identify new approaches to testing for rejection risk. We will also continue to longitudinally follow over 300 recently transplanted recipients to learn more about the individual factors that contribute to the development of complications.
Development of an early-phase clinical trial of stromal stem cells in high risk corneal transplantation
One of the greatest remaining challenges to successful corneal transplantation is the safe prevention of rejection and transplant failure in those whose cornea is already inflamed or who have previously rejected a transplant. Under these “high immunological risk” conditions, rejection commonly occurs and extended use of strong immune suppressive medications is frequently necessary.
Laboratory research carried out over the past 3 years by VISICORT researchers at the National University of Ireland, Galway and Orbsen Therapeutics Ltd. has now shown that stromal stem cells (often called mesenchymal stem cells or MSCs) from an unrelated donor given intravenously in the week before a high-risk corneal transplant greatly reduce the frequency of rejection by modulating the anti-donor immune response. We are now excited to have begun the process of testing the safety and feasibility of this new treatment approach in an early-phase clinical trial involving patients who will be receiving a second or greater corneal transplant at the Charité University Hospital in Berlin.
Development of the clinical trial protocol and procedures will be a major part of the VISICORT research agenda for the next 6 months. This will bring together expertise in therapeutic stromal cell manufacture at NUI Galway’s Centre for Cell Manufacture Ireland (CCMI); in early-phase clinical trial and regulatory affairs at Charité University Hospital and in clinical high-risk corneal transplantation at Charité, Aarhus University Hospital, Royal College of Surgeons of Ireland, University of Bristol and Centre Hospitalier Universitaire de Nantes.
Reflecting on the meeting, VISICORT coordinator, Prof. Matt Griffin of NUI Galway’s Regenerative Medicine Institute (REMEDI) commented: “It has been an exciting journey to reach the point at which we are now in a position to drive toward the major goals of the project that was conceived over three years ago. Our greatest resources have been the diverse expertise and, especially, the energy and collaborative spirit among the research teams that we have built at each partner site. I am greatly looking forward to keeping our momentum going in the same fashion over the next year so that we can deliver strongly on the promise of this project.”