The Regenerative Medicine Institute (REMEDI) at NUI Galway was delighted to host a visit by winning essay writers from St Nathy’s College, Ballaghdereen, Co. Roscommon. Each of the winning students had written an essay on the topic of stem cell, outlining the history of their discovery, and their potential to revolutionise the treatment of a range of medical conditions. The winning students – Michael Raleigh (1st), Tom Murray (2nd), Mohammad Hamid (3rd), and Annie Quinlan (3rd) – and John Guilfoyle, their teacher, were treated to a tour of REMEDI’s facilities. The competition was initiated by Oonagh Redmond, a teacher at St Nathy’s, and was organised by members of the ADIPOA-2 team. Prizes were sponsored by ADIPOA-2, VISICORT, and REDDSTAR.
VISICORT has produced a new brochure to promote the project, and to explain its aims, objectives, and approach to a general audience. Copies of the brochure can be downloaded here.
A recently published study in Transplantation Proceedings presents changing trends in corneal transplantation (CT) from Italy. The Corneal Transplant Epidemiological Study (CORTES) presents seven years of data, 2002 to 2008, from a prospective study which included over 13,000 CT. In general, trends were driven by changing clinical practise and mirrored similar trends observed in Western countries over the same period. The study demonstrated the marked transformation in surgical approach to CT from Penetrating Keratoplasty to Endothelial Keratoplasty in recent years. Of particular relevance to VISICORT is the 20% increase observed in re-grafts over the period; regraft was the second highest indication for corneal transplant over the study period. Regrafts are considered as high-risk transplants and VISICORT’s immunomodulatory stem cell therapy aims to provide novel treatment for high-risk transplant recipients.
A recent study from one of the five clinical sites for VISICORT, Bristol Eye Hospital, reports that systemic immunosuppression appears to improve long-term graft survival in corneal transplants at high risk of rejection.1
Lead author of the study, Dr Sing-Pey Chow, reports: Immunological graft rejection remains the leading cause of graft failure in corneal transplantation. Systemic immunosuppression with medications such as tacrolimus and mycophenolate mofetil has been successfully used in renal and liver transplantation to improve graft survival. They are also used in corneal transplants at high rejection risk to prevent graft rejection, with the aim of improving graft survival.
This retrospective study reported graft and visual outcomes from 35 full-thickness corneal transplants at high risk of rejection in 29 patients receiving systemic immunosuppression, mainly with tacrolimus or mycophenolate mofetil as monotherapy. With the longest follow-up duration reported to date in high-risk keratoplasty recipients on systemic immunosuppression, 5-year graft survival in this cohort was 73.5%. Rejection episodes occurred in 14 grafts (40%), and episodes were reversible in 10 (71%) grafts. Average time to first rejection episode was 9.9 months, ranging from 1.2 to 15.2 months.
Severe systemic side effects occurred in 3 patients (10%), necessitating cessation of their systemic immunosuppression. This highlights the importance of diligently monitoring patients while they remain on these medications, as well as working closely with physician colleagues to optimise patient outcomes.
Along with co-authors Stuart Cook and Derek Tole, Dr Chow states: Over the next few years, VISICORT will generate a better understanding of adverse immune reactions to tissue transplants as biological samples from over 700 corneal transplant recipients in Europe and the UK is systematically profiled. This will in turn lead to new developments in surveillance, prevention and management of corneal transplantation, particularly for those at high risk of rejection.
This study was presented at World Cornea Congress 2015 in San Diego.
1 Chow S-P, Cook SD, Tole DM. Long-Term Outcomes of High-Risk Keratoplasty in Patients Receiving Systemic Immunosuppression. Cornea 2015, forthcoming.
New data from UK Transplant Registry shows similar 2-year rejection rates for full thickness and endothelial corneal transplants in first-time recipients
Corneal transplantation involves the replacement of damaged cornea with donor tissue. For some of the commonest forms of corneal disease, there are currently two primary approaches to transplantation: Full-thickness, or penetrating keratoplasty (PK), which involves the replacement of the entire cornea, and endothelial keratoplasty (EK), which involves the selective replacement of the diseased layer of the cornea, leaving healthy areas intact. Over the past 15 years, EK has emerged as the preferred form of transplantation in cases of visual loss due to endothelial dysfunction. EK offers a number of advantages, by comparison with PK, including possible lower incidence of transplant rejection.
However, the theoretical advantages of EK have not always been reflected in the clinical data. To date, published studies have reported widely variable rates of rejection and subsequent graft failure following EK.
Newly published data from the UK Transplant Registry has provided further evidence that EK does not result in a lower incidence of transplant rejection and graft failure. The authors of ‘Transplant Rejection Following Endothelial Keratoplasty and Penetrating Keratoplasty in the United Kingdom: Incidence and survival’ report the results of 3,486 corneal transplants carried out in the UK for two specific corneal diseases and conclude that ‘there is no significant difference in rejection-free survival between EK and PK.’ They also report that the presence of inflammation can be an important risk factor for rejection suggesting that attention to its control before and following surgery is important. This finding highlights the importance of VISICORT’s work to investigate the markers of transplant rejection and to develop new therapies to control post transplant inflammation.
Prof. Jesper Hjortdal (Aarhus University Hospital), who leads the VISICORT Clinical Study Group comments: Immune reactions (rejection episodes) towards transplanted corneal tissues are common and a rejection episode often results in failure of the corneal graft. In the UK study follow-up was missing for 10-20% of the operated patients, which actually is superior compared with many other registries. Smaller, single clinic studies have been in-line with the UK Transplant Registry Study, although a tendency to lower rejection rates for EK was found in patients with Fuchs endothelial dystrophy (1,2). Prospective, longer-term studies extending beyond a 2-year follow-up are needed to further evaluate risk factors for immune reactions. VISICORT will provide such data within the coming years.
1. Hjortdal J, Pedersen IB, Bak-Nielsen S, Ivarsen A. Graft rejection and graft failure after penetrating keratoplasty or posterior lamellar keratoplasty for fuchs endothelial dystrophy. Cornea. 2013 May;32(5):e60-3.
2. Pedersen IB, Ivarsen A, Hjortdal J. Graft rejection and failure following endothelial keratoplasty (DSAEK) and penetrating keratoplasty for secondary endothelial failure. Acta Ophthalmol. 2015 Mar;93(2):172-7.
VISICORT partners NUI Galway, Orbsen, and Pintail are involved in NEPHSTROM, a new European project, which was launched last week. NEPHSTROM involves eleven partners from Ireland, the UK, Germany, and the Netherlands, and has received €6 million funding under the European Union’s Horizon 2020 funding programme. NEPHSTROM will evaluate the clinical safety and efficacy of a next-generation cell therapy discovered by Galway-based Orbsen Therapeutics, to combat diabetic kidney disease. Find out more about the project at www.nephstrom.eu.
Our sister project REDDSTAR and Leiden University Medical Center are co-organizing EU MSC2 2015, a meeting in Leiden, NL on September 7th and 8th to bring together nine EU-funded, mesenchymal stromal cell-focussed consortia. Projects include: REDDSTAR, REACH, RETHRIM, Stellar, MERLIN, Nephstrom, SCIENCE, VISICORT and Adipoa-2. This two day, interactive meeting will be held at the Stadsgehoorzaal Leiden.
The objectives of the meeting are to:
- Enhance knowledge-sharing between EU research groups working in the mesenchymal stromal cell biology domain
- Engage with European Commission Project Officers and other stakeholders from International Society of Cellular Therapy, stem cell ethicists and the European Medicines Agency (EMA)
- Assemble trans-disciplinary research groups working across the global health spectrum but with a common focus of mesenchymal stromal cell biology
- Bring up-and-coming researchers together for networking purposes, and to explore future consortium building and international funding application opportunities
Expected impacts and outcomes:
- Provide opportunities to develop new mesenchymal stromal cell networks
- Disseminate the findings and challenges between MSC-focussed consortia
- Improve the communication potential of research, outcomes and the value of the research
- Explore potential for new commercial technologies
- Collectively enhance the quality and impact of planned clinical trials
These EU projects are:
- Boosting human capital: 20-30 positions created
- Improving the quality of life for European citizens
- Progressing the clinical translation of MSC research and developments
For queries: LeidenRM@gmail.com
Danielle Nicholson, Orbsen Therapeutics, NUI Galway and Brigitte Wieles, Project Manager LUMC
The VISICORT project marked the end of the first year of its work with a plenary meeting at the Charité Campus Virchow Klinikum in Berlin on Friday, May 29. Following an overview of the management of the project, scientists involved in the project’s preclinical workpackages reported on the research carried out in the six months since the last plenary. The meeting also heard updates on recruitment for VISICORT’s clinical trial, and the development of the sample tracking system that will allow researchers to manage the movement of thousands of samples between clinical sites, storage facilities, and research laboratories. An afternoon breakout session, held in Charité’s Eye Clinic Laboratory, provided training in sampling protocols for the clinical researchers involved in the project. The meeting concluded with a discussion on dissemination and exploitation of the project’s results.
This project has received funding from the European Union’s Seventh Framework Programme for research, technological development and demonstration under grant agreement no 602470. The material presented and views expressed here are the responsibility of the author(s) only. The EU Commission takes no responsibility for any use made of the information set out.