Ana Fernandes

UHN and U of T receive $24-million federal grant for transplant research

Christopher.Sorensen — Thu, 13 Jan 2022 18:44:18 +0000

UHN and U of T receive $24-million federal grant for transplant research

Christopher.Sorensen Thu, 01/13/2022 - 13:44

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Led by Shaf Keshavjee, a research team at UHN and U of T received $24 million from Canada's New Frontiers in Research Fund to advance technology to repair and rebuild organs for transplant (photo by Tim Fraser)

Ana Fernandes

Topic

Breaking Research

Temerty Faculty of Medicine

Toronto General Hospital

Research and Innovation

University Health Network

Researchers at University Health Network (UHN) and the ��Ƶ have received $24 million to advance technology to repair and rebuild organs outside the body for patients in need.

The project, led by Shaf Keshavjee, is one of only seven across Canada selected to receive funding in the Government of Canada New Frontiers in Research Fund (NFRF) – Transformation competition, following an international consultation.

"The Ex Vivo Lung Perfusion (EVLP) system we developed here in Toronto has revolutionized lung transplantation in the past decade. Now, it's been translated around the world to increase lung transplant access and it's being extended to other organs," says Keshavjee, a professor and vice-chair for innovation in the department of surgery in U of T’s Temerty Faculty of Medicine who is surgeon-in-chief at UHN and a senior scientist at Toronto General Hospital Research Institute.

"With this transformative grant, we now have the opportunity to take ex vivo technology to the next level, where we can repair and rebuild organs for transplant."

Atul Humar, director of the Ajmera
Transplant Centre
(photo by Tim Fraser)

Over 4,500 people in Canada are currently waiting for an organ transplant, and more than 270 die each year as the need for transplant greatly exceeds availability.

Ex vivo perfusion systems use specialized machines to maintain, evaluate and treat organs before transplant. They have a huge impact on increasing the number of organs that can be considered for transplant.

The Toronto Lung Transplant Program, led by Keshavjee, has used this technology to double the number of lung transplants performed and lives saved at UHN.

"The New Frontiers grant will allow us to advance applications for lungs and further develop ex vivo systems for other organs, such as liver, kidney, heart and pancreas," says Atul Humar, a co-principal investigator on the project, professor in the department of medicine at U of T and director of the Ajmera Transplant Centre at UHN.

Funding ground-breaking innovation

Brad Wouters, UHN's executive vice president, science and research, notes that this major grant will enable multidisciplinary teams to develop new, cutting-edge approaches to extend the time that donated organs can be used, and also enable treatment and repair of unsuitable organs to allow treatment of more patients.

It will also help the teams refine and improve equitable organ allocation guidelines for all patients, he adds.

“The advancements that this team has made and their continued success is made possible by support from provincial and federal governments, industry partners, external charitable agencies, generous philanthropy from the UHN Foundation and our incredible patient partners,” says Wouters, who is also a professor in the department of radiation oncology at U of T. “This award recognizes the tireless efforts of the team, and this support, which have been key to achieving global impact.”

The New Frontiers Research Fund was designed to support large-scale, Canadian-led interdisciplinary research projects with the potential to realize real and lasting change.

The fund falls under the strategic direction of the Canada Research Coordinating Committee and is administered by the Tri-Agency Institutional Programs Secretariat on behalf of Canada's three research granting agencies: the Social Sciences and Humanities Research Council, the Canadian Institutes of Health Research and the Natural Sciences and Engineering Research Council.

Personalized medicine for every organ and beyond

Over the course of this project, the team of over 20 researchers at U of T, UHN, national and international partner sites will develop sophisticated ex vivo platforms to:

Increase organ preservation from hours to days
Improve the immune response and organ tolerance for transplant recipients
Advance precision medicine to customize organs to each individual patient's needs

Longer ex vivo preservation prior to transplant will enable many world-first therapeutic applications that will, ultimately, create more organs for clinical transplant.

One example is to use gene therapy to make an organ more like the recipient's cells and help to address the current hurdle of organ rejection by the immune system. Researchers at UHN are also working on changing an organ's blood type so the sickest people can get access to the next available organ, instead of waiting for one that exactly matches their blood – a delay that currently can take several months before a match is found.

Another transformative goal is to use medicines and light therapies in the ex vivo circuit to eliminate viral or bacterial infections that previously prevented an organ to be considered for transplant.

"This grant gives us a unique opportunity to extend personalized medicine to every organ group," says Marcelo Cypel, a professor in the department of surgery at U of T and surgical director of the Ajmera Transplant Centre, who is also a co-principal investigator on the project.

"Not only will it enable longer preservation, this research will let us treat and improve organs. It has the potential to change the paradigm in the field of transplantation."

The change will include several advanced applications, such as the engineering of new organs using stem cells with the goal to make organs available for all in need. Significant progress has already been made in generating new kidneys, lungs and tracheae (windpipe), and their applications will be tested further during the six-year project term.

With the involvement of a multidisciplinary team housed in a world-class centre at UHN, the project will bring personalized medicine to transplant, and go beyond solid organs.

Siba Haykal (photo by Rob Caruso)

Siba Haykal, plastic and reconstructive surgeon and project co-principal investigator, will lead research involving vascularized composite allotransplantation – the transplant of limbs, face, trachea and composite tissues, such as skin and muscles.

"These are very delicate tissues that can't survive outside the body for very long and are very susceptible to rejection," she explains, adding that the current treatment involves high doses of life-long anti-rejection medication for transplant recipients.

Haykal and the team want to develop a system to preserve limbs and tissues out of the body without blood flow for longer periods. This will enable the application of new cell therapies to ‘adapt’ these tissues to the recipient prior to surgery.

"Whether they have been disfigured by burns or from trauma or cancer, if they've had an amputation and need prosthetic limbs or if they require a new airway, transplantation provides hope for these patients who currently don't have many options," says Haykal, who is an assistant professor in the department of surgery at U of T.

"If we can use techniques that reduce the amount of anti-rejection medication and maybe one day get to a stage where they don't need it anymore, that would have a huge impact on the patient's quality of life."

Humar adds, "I have seen so many people who have literally been at death's door and have been completely turned around by transplant and live a full and healthy life. If we can offer that to more patients, then for me that would be an incredible achievement.

"This funding will also help us disseminate our knowledge, and facilitate other hospitals across Canada and around the world build upon what we're doing at UHN."

This story was originally posted on the University Health Network website.

Interferon speeds recovery in some COVID-19 patients, U of T and UHN study finds

Christopher.Sorensen — Tue, 16 Feb 2021 17:49:01 +0000

Interferon speeds recovery in some COVID-19 patients, U of T and UHN study finds

Christopher.Sorensen Tue, 02/16/2021 - 12:49

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(photos courtesy of UHN)

Ana Fernandes

Topic

Breaking Research

Coronavirus

Temerty Faculty of Medicine

Research & Innovation

University Health Network

A clinical study led by ��Ƶ researcher Jordan Feld and colleagues has shown that an experimental antiviral drug can significantly speed up recovery for some COVID-19 patients.

The treatment could become an important intervention for infected patients who don't need to be hospitalized and help curb community spread, while vaccines are rolled out this year.

“This treatment has large therapeutic potential, especially at this moment as we see aggressive variants of the virus spreading around the globe which are less sensitive to both vaccines and treatment with antibodies,” says Feld, an associate professor of medicine in the Temerty Faculty of Medicine at U of T and a liver specialist at the Toronto Centre for Liver Disease, University Health Network.

The study, published in Lancet Respiratory Medicine, found patients who received a single injection of peginterferon-lambda were over four times more likely to have cleared the infection within seven days, when compared to a group treated with a placebo.

“People who were treated cleared the virus quickly, and the effect was most pronounced in those with the highest viral levels. We also saw a trend towards quicker improvement of respiratory symptoms in the treatment group,” says Feld, who translated his knowledge of peginterferon-lambda usage for viral hepatitis to research on COVID-19 treatment.

Dr. Jordan Feld at UHN's Francis Family Liver Clinic

Participants with higher viral levels (above one million copies per millilitre) were much more likely to clear infection with treatment than placebo: 79 per cent in the treatment group compared to 38 per cent in the placebo group, and virus levels decreased quickly in everyone in the treatment group.

Rapid clearance has many benefits, particularly in those with high viral levels as those cases are associated with more severe disease and a higher risk of transmission to others. Among the 60 patients followed in the study, five went to emergency departments with deteriorating respiratory symptoms. Of those, four were in the placebo group, while only one was in the group which received the actual drug.

“If we can decrease the virus level quickly, people are less likely to spread the infection to others and we may even be able to shorten the time required for self-isolation,” says Feld, who is also co-director of the Schwartz Reisman Liver Research Centre and the R. Phelan Chair in Translational Liver Research at UHN.

Interferon-lambda is a protein produced by the body in response to viral infections. It has the ability to activate a number of cellular pathways to kill invading viruses.

The coronavirus that causes COVID-19 prevents the body from producing interferons, which is one way it avoids being controlled by the body's immune system. Treatment with interferon-lambda activates those same virus-killing pathways in the cells.

Because interferon activates many virus-killing pathways, resistance due to variants of the virus – which could be an issue with some therapies – is not a concern with interferon-lambda.

Interferon-lambda is different from other interferons because it uses a receptor that is only present in some tissues in the body. It is very active in the lung, the liver and the intestine – where the virus behind COVID-19 is able to replicate – but it is not active in other places leading to a lot fewer side effects than other interferons. In the trial, those treated with interferon-lambda had similar side effects to those who received placebo.

Peginterferon-lambda is a long-acting version developed by EigerBioPharma, which can be given as a single injection under the skin with a tiny needle like the ones used to inject insulin.

This phase two, double-blind randomized study was done in Toronto with a total of 60 participants – half of whom received the drug and the rest a placebo. The study was conducted from May to November of last year, with referrals from six outpatient assessment centres.

Additional studies are ongoing at U of T, Harvard University and Johns Hopkins University with peginterferon-lambda in hospitalized patients, and in settings where it can be used to prevent infection in those who have been exposed.

The clinical trial was co-led by Mia Biondi, nurse practitioner and researcher at UHN, Christopher Kandel, infectious disease specialist at Michael Garron Hospital and trainee in U of T's Temerty Faculty of Medicine, and Bettina Hansen, of U of T's Institute for Health Policy, Management and Evaluation in the Dalla Lana School of Public Health and senior statistician at UHN.

The study was supported by the Toronto General & Western Hospital Foundation, U of T's Toronto COVID-19 Action Fund and the Ontario First COVID-19 Rapid Research Fund. Medication was supplied by EigerBioPharma.

This article was originally published by the University Health Network.