To mark Organ Donation Week, the NIHR Biomedical Research Centre (BRC) at Guy’s and St Thomas’ NHS Foundation Trust and King’s College London is sharing a series of articles and videos which explore our research in the field of organ donation, rejection and tolerance in transplantation.
Professor Steven Sacks leads the BRC’s Transplant research theme and is the Director of the MRC Centre for Transplantation, Head of Division of Transplantation and Mucosal Biology at King’s College London.
Can you tell us about how your research aims to improve the life span of transplant patients?
When the kidney is transferred from the donor to the recipient, it undergoes an inflammatory reaction caused by the transplant procedure. A major part of this comes from within the kidney itself. Our research has been to identify targets to stop inflammatory activity using specially designed therapeutics.
Here at King’s, we are building therapeutic inhibitors out of natural proteins that protect our cells with the aim of reducing the inflammatory response. These are modified by attaching a tail so that after being introduced into the blood circuit of the donor kidney they remain in the organ in the critical week after transplantation to maintain the effect.
The first of this new class of drugs is being tested in a clinical trial to see if the recovery of the transplanted kidney is improved. A second therapeutics NB word missing here? Doesn’t make sense designed to coat the blood vessels of the kidney and prevent clotting of organs transplanted into high risk patients.
The concept is that by protecting the donor kidney at the time of transplantation, the treated kidney will make a more effective recovery and be less likely to trigger rejection by the immune system of the recipient. Therefore there will be greater hope for long term survival of the transplant and of thepatient, and less need for immunosuppressive drugs.
These approaches are also being taken up by King’s College London colleagues working on liver cell transplantation in children and on pancreatic islet transplantation to cure diabetes. Although at an early stage of development, these projects show promise to overcome some of limitations in current clinical practice related to over-activity of the inflammatory and clotting systems.
The long-term goal is to combine these protective therapies with tolerance inducing therapies, which are designed to coax the immune system into accepting the foreign organ as ‘self’. It is likely that both will work better together than if used independently.
How can research impact on the life of future transplant patients?
Our research aims to extend the life of the transplant, and therefore the patient, by improving immediate recovery and inducing a state of long-term graft acceptance without the need for the immunosuppressant drugs which can have serious side effects.
Some of the methods we employ could make it possible to increase the number of donor organs who are considered suitable for transplantation, so more people can benefit from successful organ donations.
Can you describe some of the other interesting collaborations you have formed working at King’s College London?
The main collaborations have come through links with the Department of Genetics, the Department of Imaging Sciences and the Stem Cell Centre.
Colleagues in Genetics have enabled members of the Transplant research theme to examine whether genetic markers can help read, or even predict, the inflammatory and immune response, with a view to adjusting patient decisions accordingly. This joint effort has enabled the theme to create and lead a UK and Ireland network of transplant centres, which together have conducted a genome-wide search for markers associated with different transplant outcomes, including rejection and graft loss. The internal biomarker team, supported by the Genetics team, has been able to launch immune monitoring studies that have highlighted some promising results. In particular, we are now able to identify markers of immune tolerance and therefore conduct drug-minimisation trials in kidney and liver transplant patients.
Collaboration through the Imaging department has produced new methods for tracking the inflammatory and immune responses by external body imaging. This has helped to detect the inflammatory ( in particular the ‘complement’) system when it has been activated. This will be useful for monitoring the effect of treatment, as well as disease activity in different organs including heart transplants. Their efforts have also helped design imaging tools to follow the fate of regulatory T cells, a type of helpful white blood cell of the immune system given for therapy to prevent rejection. New imaging tools have also made it possible for other researchers to visualise the architecture of the immune system, and understand from where it mounts an attack on the transplant organ.
Looking ahead to the future of organ repair and replacement through stem cell approaches, we have formed a research collaboration with the Centre for Regenerative Medicine and Stem Cells. Together we have formed the immunology hub of the ‘UK Regenerative Medicine’ programme, with outreach to centres in Oxford, UCL, Imperial, Birmingham and Newcastle. The centre brings together expertise in inflammation and immunity with experts in retinal, cardiac and liver repair.
Finally, what are the challenges of having a demanding schedule as both a researcher and a clinician?
The main challenge is to handle multiple tasks well. This works when the tasks are inter-related and complement each other. The main pleasure, help, chore and solution rolled into one is to work and lead in coherent teams. This is a coping and productive strategy, which relies almost entirely on a group of creative, responsive and responsible colleagues with a unified vision. Thus the challenge and fulfilment are part of the same entity. The centre and theme concept is what brings these together.
Find out more about the BRC’s work in the field of organ donation, rejection and tolerance in transplantation.
There are a series of events taking place at Guy’s and St Thomas’ to celebrate Organ Donation Week which runs from Monday 5 to Sunday 11 September. Visit the Trust’s website to find out more.
Further reading: Hundreds saved by transplants at Guy’s