Transplant Research Newsletter – Summer 2016

Transplant Research Newsletter – Summer 2016

Venture Grants Research Program

Your donations at work making a difference to transplant patients

A second chance at life through organ transplantation is an incredible gift – one that has become an effective treatment for end-stage organ failure. But, transplant is not a cure. At least not yet. This is where the Transplant Research Foundation of BC (TRF) and your donations are making a difference!

We interview Lori Lothian, TRF Chair, and Dr. Alice Mui, our Scientific Director, about the Venture Grants research funding program.

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TRF is focused on transplant research. Why is that important?

Alice: Without research, there would be no advances in transplantation medicine. It is only through research that we are able to better address the needs of transplant patients and those facing organ failure. For example, surgeons had already figured out by the 1900s how to stitch blood vessels together, and many attempts were made in the next 50 years to transplant organs (mainly kidneys) into people. These kidneys would inevitably be rejected by the body. Research finally revealed that our body has a system that distinguishes between self and non-self – and we now know this as the immune system. With this realization, the first successful kidney transplant occurred between identical twins in 1954. Subsequent research into developing immune suppressive drugs that can be used for transplants between genetically non-identical individuals made organ transplant a feasible therapy for anyone, even if they didn’t have an identical twin. More research advances now even allow transplant of more complex tissues, such as a hand or uterus, and in 2014 a uterine transplant resulted in a live birth! Without research providing us with an understanding of transplantation, including blood types, rejection, and new technologies to revive dead organs, there would be no transplantation. Even if we solve the problem of shortages in organs available for transplant, without research to understand the complications and challenges of transplanting an organ into a human being, it would be irrelevant.

Lori: I completely agree. I don’t think we, as transplant recipients or as candidates for transplant for that matter, appreciate how much we have benefited from transplant research over the last 50 years. Every year breakthroughs are being made in research that lead to better and better outcomes and longer and longer survival rates. I also don’t think that many of us are well prepared for the challenges that follow our surgery. Even with great outcomes, there will be inevitable bumps in the road, and we rely on the knowledge created through research to help us recover from these and continue to live productive lives.

What is the TRF Venture Grants program?

Lori: The TRF Venture Grants Program provides funding to innovative research projects across British Columbia that have the potential to significantly impact organ transplantation.

Alice: What’s really unique about the Venture Grants competition is that it is focused on supporting new areas of research that are in a pilot/feasibility stage. For example, we might fund projects that have completely new hypotheses, techniques, or ideas that have never been studied.

Lori: The Venture Grants fill a real need in the research community because even though every breakthrough starts with the seed of an idea, it’s not easy for researchers to find the funds they need to get the seed planted and growing. That’s what the Venture Grants do.

How is it funded?

Lori: The Venture Grants program is 100% funded by donations! It is a very unique program in this sense. Our donors know that their money is going directly to fund innovative transplantation research in BC that has the potential to change the lives of people facing organ failure. There are no other programs like this in Canada.

How much money does the TRF give out and how many projects are funded through this program?

Lori: Venture Grants are awarded annually and provide $25,000 per project. This may seem like a small amount, but it’s enough for researchers to test their ideas and generate the data needed to apply for funds from larger granting agencies (such as the Canadian Institutes of Health Research). These larger agencies need more than just a great idea, they need to see data showing an idea is already correct before they will even consider funding it. Although the Venture Grants are small, they deliver a big punch!

Alice: Each year we get eight to ten project proposals and fund between two and four research projects, depending on the recommendations of the  scientific Peer Review committee and TRF’s financial ability.

Lori: Since 2004, TRF has given out over $800,000 in research dollars, funding over 50 transplant research projects in British Columbia!

Alice: It has been exciting to see the impact this program has had on transplant research in BC. Venture Grants have allowed clinicians to develop ideas based on what they see in patients. The grants have also helped them recruit researchers who had not previously applied their expertise towards solving problems in transplantation.

How does the TRF decide what projects to fund?

Alice: This program, like all the research we fund, is peer reviewed. The Peer Review Committee of the Venture Grants Program brings together experts in the field of transplantation to review the applications and then recommends the projects they feel are the strongest scientifically. his ensures that the projects selected for funding will, by their nature and design, contribute to scientific knowledge in the field of transplantation. From this, the TRF board decides how many they can fund. This year we were able to fund three exciting transplant related projects.

What types of projects are funded?

Lori: Projects have ranged from foundational sciences to more clinically-oriented investigations. All have a vision of how the outcome of the research would ultimately apply in clinical practice to improve the lives of transplant recipients. For example, TRF was an early funder of the PROOF (Prevention of Organ Failure) Biomarkers Study (www.proofcentre.ca) to develop a method for detecting organ rejection through a simple blood test as an alternative to traditional biopsies. The Proof Centre of Excellence is now a world class research centre working to produce a new generation of patient-specific biomarker-based blood tests to better guide care for heart, lung and kidney patients.

Alice: Yes, and a number of projects funded have explored the challenges of immunosuppression including how to promote tolerance of transplanted organs and how to deliver immunosuppressant therapy in a more effective, less toxic way.

Lori: Two of the projects we funded last year involved research aimed at increasing the number of organs available for transplant. One project was science based and one targeted clinical practice.

How do the Venture Grant projects contribute to knowledge in transplantation?

Alice: All our projects increase our knowledge in the area of transplantation and at the very minimum lead to new insights. Excitingly, many of our projects have led to advances that are close to being used in human transplant recipients.

Lori: As transplant recipients, we want smart people thinking about our challenges and the Venture Grants encourages and supports the research community to think creatively about problems in transplantation. We’re so fortunate to have a robust environment for transplant research here in BC and I think the Venture Grants have a role in supporting that.

2015-2016 Venture Grant Winners

[gdlr_personnel columns=”1″ type=”static” style=”box-style”]
[gdlr_tab title=”Dr. Kevin Harris” author_image=”https://www.trfbc.org/wp-content/uploads/2016/06/kevinharris.bmp” ]Children who have had a heart transplant are at risk for developing a disease called cardiac allograft vasculopathy (CA V) where their coronary artery walls thicken over time. Sadly, CA V is responsible for 1 in 4 patient deaths. The current way to look for CA V is to use a technique called angiography where dye is injected directly into the coronary arteries and imaged. However, the limitation of angiography is that it can only detect late stage disease and therefore treatment is less likely to work. For this project, Dr. Harris will use a new imaging technique called optical coherence tomograph (OCT) to detect problems developing in children’s heart transplant grafts early enough to treat the problem. OCT is an imaging technique designed for use in adults that is beginning to be used in children. Dr. Harris has already performed a preliminary OCT study and found that OCT detects artery thickening earlier than angiography in pediatric heart transplant recipients. He will now use OCT to follow these children over time in order to establish this technique for reliable, routine use.[/gdlr_tab]
[gdlr_tab title=”Dr. Amee Manges” author_image=”https://www.trfbc.org/wp-content/uploads/2016/06/ameemanges.bmp” ]Organ transplant patients are at increased risk of developing highly antibiotic resistant infections as a result of their transplant surgery, lengthy hospitalization and repeated use of antibiotics during their medical care. The source of these multidrug-resistant bacteria is the patient’s own gut. In this study, Dr. Manges will test whether fecal microbiota transplantation (FMT) can remove highly drug-resistant bacteria from the gut of kidney transplant patients. FMT is a therapy that involves the infusion by enema of well screened, healthy donor stool into a patient’s gut. FMT can replace the gut microbial community containing these drug-resistant bacteria, with a microbial community characterized by more beneficial organisms with lower levels of antibiotic resistance, thereby lowering a kidney transplant patients risk of hard to treat, post-transplant infections. The goals of this study are to confirm that FMT can eliminate drug resistant bacteria from the gut of transplant recipients, and to determine how long the patient remains free of these drug resistant organisms.[/gdlr_tab]
[gdlr_tab title=”Dr. Sam Wiseman”  author_image=”https://www.trfbc.org/wp-content/uploads/2016/06/samwiseman.bmp” ]The thyroid gland makes hormones which control how quickly the body uses energy, makes protein and controls the body’s sensitivity to other hormones. The thyroid is often removed because of cancer or benign disease (several hundred thousand per year in North America), and loss of thyroid function leads to severe illness and disease so these people take thyroid hormone (thyroxine) replacement therapy. But people receiving thyroxine still experience side effects (weight gain, depression, headaches, cardiovascular disease) because taking thyroxine is not the same as having a functional thyroid gland that can monitor the body’s metabolism and produce hormones in real time as it is needed. Transplantation of the thyroid gland back into these people would give better metabolic control. Dr. Wiseman will test whether thyroid glands obtained from deceased donors can be placed inside a special pouch and implanted into a recipient. The pouch will protect the thyroid gland from attack by the immune system so the recipient can live a normal life with a functioning thyroid gland without
having to take anti-rejection drugs.[/gdlr_tab]
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