Why our work is important
Transplantation is an effective treatment for patients with established organ failure, but rejection by the immune system remains a major challenge. Clinical success in preventing and treating transplant rejection is achieved using increasingly potent immunosuppressive drugs to inhibit the immune response.
Using combinations of immunosuppressive drugs can be effective, at least in the early period after transplantation. The problem is that transplant recipients have to take these drugs for the rest of their life and most of the immunosuppressive drugs available at the moment suppress the entire immune system, not just the part that is trying to destroy the transplant. As a result, transplant recipients have an increased risk of infection and cancer and they can also suffer from side-effects associated with the long term use of these drugs. To make sure that the right balance between under and over immunosuppression is achieved and maintained, transplant recipients have to see their doctor frequently.
Interestingly, different types of transplant, for example kidney compared to a liver transplant or composite vascularised transplant, trigger a different set of responses from the immune system. Understanding the diversity of the mechanism of rejection and actually seeing how rejection damages the transplant will help us to develop more specific therapies to control post-transplant immune reactions.
In any normal immune response, for example when we fight a virus infection, the correct level of control of the response is essential. A half-hearted response will not clear the infection, while one that is excessive will lead to unwanted tissue damage. Understanding how the immune system is controlled and how it promotes the development of specialised cells that can regulate its activity holds the key to the development of novel approaches to manipulate immune responses more selectively after transplantation.
Our research addresses the current unmet needs in clinical transplantation including
* The shortage of organs available for transplantation
– Many more patients are waiting for a transplant than will receive a transplant this year (view the statistics on organ donation at: http://www.organdonation.nhs.uk/ukt/newsroom/fact_sheets/transplants_save_lives.jsp)
* Preventing and predicting transplant rejection
- Each time rejection happens, the transplant is damaged. If we could completely prevent rejection or at least predict when it was going to happen more accurately, the length of time a transplant survives would increase
* Improving long term outcomes – quantity of life
- Finding ways to control the immune system more selectively would also increase the length of time each transplant survives.
* Reducing the side effects of immunosuppressive drugs – quality of life
- Non-specific immunosuppressive drugs give rise to other medical conditions including infection, cancer, hyperlipidemia etc. Controlling the immune response to a transplant more selectively will also reduce these side effects.
We are investigating how to :
(i) increase the selectivity of immunosuppression such that only the destructive responses the immune system makes against the transplant are suppressed
(ii) predict the when rejection is going to happen more reliably to enable anti-rejection treatment to be started before the transplant has actually been damaged by the immune response
Advances in each of these areas would allow immunosuppressive drug therapy to be tailored to the specific needs of the individual transplant recipient. In other words, the development of personalised medicine for each individual transplant patient
For more information about the Organ Donation Scheme please see the link below: