Identifying new treatments for cytomegalovirus (CMV) after kidney transplant
Human cytomegalovirus (HCMV) remains a significant problem for kidney transplant patients
CMV is carried by approximately 60% of people in the UK and individuals with normal functioning immune systems are unaware they have it as there are rarely any symptoms associated with infection. HCMV can usually be controlled by the immune system and remains dormant. Once you are infected it stays in your body for life.
Transplant patients are immune suppressed, however, and this means that their HCMV is usually problematic in these individuals. This is because the medications used to protect their new kidney also impact how well their immune system functions. For these individuals, active HCMV infection can cause serious problems potentially leading to severe illness and an increased chance of kidney rejection.
Kidney transplant patients wait an average 2-3 years for a donor organ. Therefore, it is not effective to reject a kidney for transplant because it is infected with CMV.
There is a need for new treatments that target the virus before transplantation
Currently, there is no vaccine against CMV. There are antiviral drugs that target the virus, but they have potentially harmful side effects, especially in kidney transplant patients.
In addition, these antivirals target the virus when it is active and are not effective when the virus lies dormant. Therefore, there is a need for new drugs that target the virus in the donor organ before transplantation where replication of the virus would cause disease in the absence of a fully functioning immune system.
Meet the researcher
Dr Emma Poole, from the University of Cambridge, has received a Professor Michael Nicholson Research Project Award of £244,000 with Dr Sarah Hosgood, Professor Michael Nicholson (University of Cambridge) and Dr Michael Nevels (University of St Andrew’s).
The funding award will enable them to test new compounds that may inactivate CMV in donor kidneys before they are transplanted.
Testing new compounds in the human kidney
Emma and the team have recently identified two new drug-like compounds that target HCMV when both active and dormant. They will now test these compounds to see if they can target CMV in the human kidney to see if it is possible to inactivate the virus before a kidney is transplanted.
This can be described as a ‘block and lock’ strategy in which they will use these compounds to ‘block’ the virus from reactivating in the donor kidney, and ‘lock’ it in its dormant phase – which means it cannot replicate and cause symptoms.
Firstly, they will look at human kidney cells in the laboratory and then use a normothermic perfusion system to introduce the new compounds to human kidneys that have been donated for research. They also want to better understand how these compounds work against HCMV.
What is normothermic perfusion?
During normothermic perfusion, the kidney is placed on a machine whilst a blood-like substance and nutrients are pumped through it allowing the kidney to work as it would in the body. Under these conditions, drugs can be added to see what effect they have. This is an important way to look at potential new ways of improving condition of donated kidneys.
What does this mean for kidney transplant patients?
This research may make it possible to treat CMV in donor kidneys before transplantation, reducing the risks associated with this infection in kidney transplant patients and keeping donated kidneys healthier, for longer.
“Human cytomegalovirus is particularly important in a transplant setting where recipients are immunosuppressed, and their transplanted kidney is at risk of rejection. I am delighted to be funded by Kidney Research UK to test new drug-like compounds that may be effective in treating CMV in the donor kidney, before it is transplanted.
The results of these studies will tell us whether these compounds should be further developed and potentially tested in clinical trials in the future. This is an exciting prospect which will bring us closer to improving outcomes for kidney transplant patients.” Dr Emma Poole.
More research for transplantation
Personalising treatments for focal and segmental glomerulosclerosis patients receiving a kidney transplant
Blocking the immune response to protect transplanted kidneys so they function better and last longer
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