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New research at UHN shows light could be the answer to get rid of virus infections in donor organs – a milestone with the potential to dramatically increase access to life-saving transplants.
A pre-clinical study is showing for the first time the effectiveness of using light-based therapies to inactivate hepatitis C virus in a donor organ – in this case in donor lungs – meaning the virus from an infected donor organ becomes unable to infect a patient during the transplantation process.
When translated to clinical practice in the future, these findings could mean regularly accepting organs without concerns of transmission, which universally occurs without any treatment.
This innovative research was a collaborative work between UHN and University of Sao Paulo (USP), in Brazil, and revealed that therapies using Ultraviolet C (UVC) light and Photodynamic Therapy (PDT) may completely inactivate the virus before transplantation.
The results were published online today in
"We observed that light therapies have the ability to lower the viral load and make it non-infectious," says Dr. Marcos Galasso, a PhD student at the Latner Thoracic Surgery Laboratory and first author of the study. "Although you can still detect fragments of the virus after the treatment, we showed after exposure to the light therapies, the virus could no longer infect liver cells."
The research team was led by Dr. Marcelo Cypel, Surgical Director of the UHN Transplant Program and scientist at Toronto General Hospital Research Institute (TGRI).
The team treated nine rejected human lungs that were infected with hepatitis C, using light therapies and the
Toronto Ex Vivo Lung Perfusion System (EVLP) – technology developed at TG in 2008, which perfuses organs outside of the body and allows for further assessment of organ suitability for transplant.
They showed that virus exposed to the light therapy could not infect liver cells, work carried out in the laboratory of Dr. Jordan Feld, R. Phelan Chair in Translational Liver Research and an expert on hepatitis C treatment.
A customized device was developed to deliver the light therapies into the EVLP circuit.
The results showed PDT was the most effective therapy to clear the virus from the lungs. However, the researchers also concluded that the remaining virus left after UVC treatment was inactivated, meaning both therapies could be successful in completely avoiding infection to a transplant recipient.
"Although PDT was more successful in the lab in lowering the virus count, both PDT and UVC were able to completely inactivate the virus and prevent it from infecting cells," says Dr. Galasso. "Our study also shows both therapies are safe for patients waiting for a transplant.
"Since UVC is a simpler therapy, we decided to start the next phase there."
PDT requires the use of medication which is activated by light (in this project methylene blue was used). On the other hand, UVC is a therapy that only requires direct irradiation of the liquid going through the EVLP system.
Based on this study, Dr. Cypel's team has recently started to apply UVC treatment clinically to donor lungs with hepatitis C. The initiative is part of
an ongoing clinical trial which is a first in the world in assessing the safety of transplanting hepatitis positive organs to non-infected patients using the ex vivo technology.
"If we can find a way of 'curing' these lungs before transplantation, we won't even need to treat the recipients because they will never get infected," he says.
"We can lower the risks for the patients and the costs to the healthcare system."
Waiting for a life-saving transplant
Dr. Cypel explains that being able to use hepatitis C positive organs would have a high impact in transplant waiting times.
With the opioid crisis, he says, clinical teams across North America have observed a spike in organ donors that test positive for the virus. Dr. Cypel estimates that regularly accepting hepatitis C positive donor organs would increase the number of lungs available for transplant by 1,000 per year in the North America.
Currently, approximately 2,600 lung transplants are done per year in Canada and the United States.
"This study is a first step in assessing how light therapies can potentially clear donor organs from viral infections," he says. "If we are able to routinely translate this to clinical use, this could help reduce waiting times for organs considerably."
As of 2017, more than 240 patients were waiting for a lung transplant in Canada.
This work was supported by the Canadian Institutes of Health Research (CIHR Project Grant), Medicine-by-Design Cycle 1 Team Projects Award (# C1TPA-2016–07), Toronto General & Western Hospital Foundation (Grant # 1013612, UHN Transplant Program, and XVIVO Perfusion. The research team also thanks the efforts and support of Trillium Gift of Life, which co-ordinates organ and tissue donation across Ontario and without whom these studies would not have been possible.
Dr. Cypel is a founders of XOR Labs Toronto and a consultant for Lung Bioengineering.