The leadership of MNIT Research has been assumed by Ian Hutchinson, PhD. Ian is the Director of Research and holds the S. Mark Taper Research Chair at MNIT. His guidance and experience has been instrumental in raising the quality and quantity of MNIT Research.
Research at the Mendez National Institute of Transplantation can be divided broadly into three areas:
1. Studies of the diseases that lead to end-stage organ failure.
The notion driving this work is that prevention of organ failure will serve the transplant community by saving some patients from transplantation at all, reducing transplant waiting lists and reducing the gap between the number of patients who need a transplant and the availability of suitable organs.
In the case of kidney transplantation, this overlaps with research in Nephrology and the MNIT seeks to build strong ties with colleagues in that specialty.
The MNIT is unique among other institutes of its kind in that it has access to samples and clinical information on about 4,000 patients whose kidneys failed, mainly as a consequence of diabetes or hypertension.
Researchers at the MNIT recently discovered a genetic link between hypertension and renal failure. Such insights may guide treatment to prevent renal failure in patients who are at risk because of their underlying disease.
2. Studies of the donor organ and transplant function after transplantation.
There is a grave shortage of suitable organs for transplantation. Organs that could and should have been transplanted are discarded while some organs that are transplanted function only after a period of delay or never function. There are three factors that affect successful transplantation:
- the use of ‘extended criteria donors'
- the determination of the quality of the organ about to be transplanted
- the passage of infectious disease from donor to recipient with the grafted organ.
Nowadays, organs are harvested from donors who would previously have been considered unsuitable. Extended criteria include age, cause of death and any underlying medical condition.
Researchers at the Mendez National Institute of Transplantation study genetic profiles associated with delayed graft function and research organ perfusion to develop a set of biomarkers that indicate likely graft function after transplantation.
The MNIT also strives to develop new methodologies to detect infectious agents in donors, to eliminate the transfer of disease from donor to recipient and to monitor infection and its treatment after transplantation.
3. Studies of the recipient response to transplantation.
The outcome of transplantation depends on the type and strength of the immune response against the transplanted organ and the way the recipient absorbs and handles the drugs given to suppress transplant rejection.
The graft is seen as foreign by the recipient because protein molecules, the so-called ‘transplantation antigens’ or HLA molecules, on the surface of graft cells are recognized as being different or mismatched.
The rejection response is under genetic control, so the strength of the recognition and reaction to the graft can be predicted before transplantation. Furthermore, the most appropriate drug therapy is influenced by genetic differences in the way the drugs are absorbed, broken down or work in individual patients.
Work at the Mendez National Institute of Transplantation includes a novel technology to reduce the presence of transplantation antigens on the graft, leading to less incidence of rejection. This project is at the proof of concept stage.
Access to the thousands of samples that the Institute has from past transplant recipients facilitates research into the genetics of graft rejection and differences in response to immunosuppression.
Researchers aim to develop a genetic profile predicting the optimal treatment of each and every transplant recipient.
Researchers at the Mendez National Institute of Transplantation have identified a genetic profile that predicts the development of post-transplant diabetes. Having identified patients at risk, researchers plan to test a prophylactic protocol avoiding diabetogenic drugs and giving pre-emptive anti-diabetes medications.
This approach will be extended to the other side effects of transplantation and immunosuppression. Researchers are working on some new genetic variants they have found to be associated with leukopenia (bone marrow suppression).
One of the major problems in treating transplant recipients is to know whether they are mounting a sub-clinical response to their graft. This has been termed ‘smouldering rejection’ and is a part of the process of chronic rejection to which the majority of transplants succumb.
The principal difficulties with past and present attempts to monitor graft rejection are the lack of specificity and sensitivity of the assay methods.
A new approach is being developed at the Mendez National Institute of Transplantation that will enable the monitoring of immune responses at the single cell level. This enables researchers to both follow the course of events and select the optimal therapeutic options to manipulate the immune response accordingly.