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This summer, we worked very hard to ensure each dollar donated towards the Enduring Hearts mission was spent in the best way possible to help improve and save the lives of children who need a new heart.

Enduring Hearts has funded three new ideas, two are new and safer ways to diagnose rejection and one is a way to help our kids graduate from childhood to adulthood. Two of these funded ideas could even lead to ways to reduce rejection and reduce the uncertainty of whether our kids are taking just the right medications to prevent rejection. For those of you who would like a few more details, let’s borrow a few highlights from these three teams’ descriptions.

New knowledge from the team from Emory University is that our bodies have a type of cell that have a label on them, CD122, that are found in hearts undergoing rejection. Over the next 2 years, this team will use an experimental model of rejection following heart transplantation to determine if increased numbers of CD122 cells can be detected in rejecting hearts from outside the body. The same tool used to detect CD122, an antibody, will also be tested to see if giving that antibody will prevent later rejection.

A team from Children’s Hospital Wisconsin has early indications that the circulating blood cells will tell us when there is an increased risk for rejection. Enduring Hearts will fund the Team to test these cells when our kids are having a heart biopsy to see if the gene activity in the cells can correctly identify if there is rejection on the heart biopsy. This same approach could also be applied as a test to tell us if the immunosuppressive medications that our kids take every day are at the correct dose to prevent rejection, not too much and not too little.

Enduring Hearts is funding a team from Toronto, Canada to try out a new way to help our pre-teens and teens safely grow up. Pediatric heart transplant recipients deal with considerable psychological and social stress from living with a chronic disease that requires daily medications and continuous medical supervision. When these patients do not adhere to treatment, they may be admitted to the hospital more often, experience organ rejection or graft loss and even death. To lessen these treatment-related burdens, new research-based practices promoting self-management and social support should be sought. The iPeer2Peer program is one such intervention that could improve patient-care management, adherence with treatment, social isolation and other health outcomes. iPeer2Peer is an online peer support mentorship program that would improve access to health information and social support.

We will learn how these work in practice over the next two years and we will share these findings with you.

For a more detailed description of each grant, read below.

Toronto, Canada Investigators - Implementation and Effectiveness Evaluation of the iPeer2Peer Support Mentorship Program within Pediatric Heart Transplantation

EH Priorities:
Development of evidence-based strategies to improve adherent behaviors, including medication adherence, especially in adolescent recipients.

Pediatric heart transplant recipients deal with considerable psychological and social stress from living with a chronic disease that requires daily medications and continuous medical supervision. When these patients do not adhere to treatment, they may be admitted to the hospital more often, experience organ rejection or graft loss and even death. To lessen these treatment-related burdens, new research-based practices promoting self-management and social support should be sought. The iPeer2Peer program is one such intervention that could improve patient-care management, adherence with treatment, social isolation and other health outcomes. iPeer2Peer is an online peer support mentorship program that would improve access to health information and social support. The proposed trial testing the iPeer2Peer program would evaluate the way the program is implemented to make sure it is feasible, adoptable, acceptable, and appropriate. The program will also be evaluated to see if it improves participant self-management skills, adherence with treatment, quality of life, social support, stress and coping. This research has a strong focus on involving patients, improving their health, and making it easier to access self-management and social support interventions. The results of this research have the ability to improve the lives of children and youth with a heart transplant.

Emory University Investigators - CD122 Directed Therapy and Non-invasive Diagnostic ImmunoPET for Heart Allograft Rejection

EH Priorities:
(1) Non-Invasive & Early Detection of Rejection
(2) Novel Targeted Immunotherapy for Heart Transplant Rejection

After heart transplantation, one of the most important and immediate threats to the success of the transplant is rejection. While all patients are at risk of rejection, usually 20-30% of patients experience rejection. The highest risk of rejection is during the first two years after transplantation and the risk decreases significantly after that time but never goes away. What is rejection? Rejection is the recipient’s immune system’s recognition and destruction of the donated heart transplant. It is characterized by the immune system’s cells moving into the transplanted tissue and killing the transplanted heart’s cells. Today, pediatric heart transplant recipients undergo endomyocardial biopsy (EMB) in order to monitor for rejection. This is a procedure where a catheter with a needle is introduced into one of the large veins of the body, and then advanced into the heart, and then the needle cuts small pieces of the heart and retrieves these samples for pathologists to review. Pathologists then make a determination of whether or not the sample shows evidence of rejection, primarily by looking for immune cells moving into the transplanted heart; they also evaluate the health of the heart cells. EMB is currently the gold standard, but there are some drawbacks. First, it is invasive, meaning patients have to be sedated and we have to introduce a catheter and needle into their body and drive it into their heart. There is a risk of injury, infection, bleeding and there can be significant radiation exposure if these procedures are done with the help and guidance of X-rays. Also, if 5 pathologists are shown the same heart sample slide, 1 or 2 of them may disagree with the other 5 on whether or not a given sample even shows rejection. Finally, because the sample only shows a small sliver of the heart, it is possible that the sample does not represent what is happening to the whole heart, and so rejection could be missed or misdiagnosed.

In this study, we propose to use ImmunoPET to detect heart rejection first in mice. ImmunoPET stands for Immuno-Positron Emission Tomography. This is an imaging test that uses a specialized probe that gives off small amounts of radiation, similar to a CT scan. The radiation is detected and turned into an image by the PET scanner. In these studies, we will perform heart transplants in animals which will then experience rejection, and we will use a radiolabeled CD122 antibody, a small protein that is highly specific and can tag the immune cells involved in rejection, as our probe. Once these cells are tagged with the CD122 probe, we will perform the PET imaging and evaluate whether or not we can detect rejection. At the time of the scans, we will correlate the scans with the same tissue analysis used in EMB, which is looking at the whole heart tissue for immune cell infiltration and rejection, and other techniques to evaluate whether or not ImmunoPET was successful in detecting rejection. We predict that ImmunoPET will be as effective or more effective than biopsy, and that we will be able to detect rejection with ImmunoPET before the transplant is fully rejected.

Furthermore, we propose to investigate whether or not CD122 can be a therapeutic target. During previous studies, we have noted that cells that infiltrate and cause skin and kidney rejection express high levels of CD122, and in those models when we blocked  CD122 with a therapeutic antibody, we were able to successfully prolong transplant survival. Given our preliminary data and prior studies with CD122, we predict detect ImmunoPET will detect rejection early before the heart shows any signs of dysfunction. Furthermore, we hypothesize that treatment with an anti-CD122 antibody will lead to a prolonged heart transplant.

Children's Hospital of Wisconsin Investigators - Plasma Induced Transcription Analysis in Pediatric Heart Transplantation as an Assessment of Rejection

EH Priorities:
Early identification of the onset of rejection through the further development of accurate non-invasive methods and strategies to detect acute cellular and antibody-mediated rejection and cardiac allograft vasculopathy.

Summary:
Children undergoing heart transplantation are at risk of developing rejection. Rejection is the process by which the body’s immune system attacks the donor heart, which may lead to heart failure and sometimes death. To help reduce the risk of rejection, all transplant recipients have to take medications to suppress their immune system. Currently, the best way of diagnosing rejection is with a heart catheterization procedure that involves taking a heart biopsy (collecting tissue samples). Catheterization based procedures are costly and have associated risks.

Our goal is to develop a blood test that reliably identifies the presence of rejection in children without the need for a catheterization procedure.

Our proposal focuses on collecting blood at the time of a heart biopsy and using that blood sample to perform an analysis on genes regulating the immune system. The results of the analysis are then compared to the results of the heart biopsy. The presence of rejection should be identified by a specific pattern of activation in immune-related genes. Other advantages of our proposed study are that it may help identify children at risk of developing rejection, help monitor the treatment of rejection, foster creation of individualized medication regimens, and expand our knowledge and understanding of the mechanisms involved in rejection.