Weekend Argus (Saturday Edition)
Organ transplant breakthrough
Great strides made in research to trick body into accepting donor organ as its own without rejecting it
IT WAS not the most ominous sign of health trouble, just a nosebleed that would not stop. So in February 2017, Michael Schaffer, 60, first went to a local emergency room, then to a hospital where a doctor finally succeeded in cauterising a tiny cut in his nostril.
Then the doctor told Schaffer something he never expected to hear: “You need a liver transplant.”
Schaffer had no idea his liver was failing. He had never heard of the diagnosis: non-alcoholic steatohepatitis, a fatty liver disease not linked to alcoholism or infections.
The disease might have no obvious symptoms even as it destroys the organ. That nosebleed was a sign that Schaffer’s liver was not making proteins needed for blood to clot. He was in serious trouble.
The news was soon followed by another eye-opener: doctors asked Schaffer to become the first patient in an experiment that would attempt something transplant surgeons have dreamed of for more than 65 years.
He would be the first to undergo a new procedure which trains the immune system to accept a donated organ as part of the patient’s body.
If it worked, he would receive a donated liver without needing to take powerful drugs to prevent the immune system from rejecting it.
Before the discovery of anti-rejection drugs, organ transplants were simply impossible. The only way to get the body to accept a donated organ is to squelch its immune response.
But the drugs are themselves hazardous, increasing the risk of infection, cancer, high cholesterol levels, accelerated heart disease, diabetes and kidney failure.
Within five years of a liver transplant, 25% of patients, on average, die. Within 10 years, 35%-40% die.
“Even though the liver may be working, patients may die of a heart attack or stroke or kidney failure,” said Dr Abhinav Humar, a transplant surgeon at the University of Pittsburgh Medical Centre who leads the study Schaffer joined.
“It may not be entirely due to the anti-rejection meds, but the anti-rejection meds contribute.”
Patients usually know about the drugs’ risks, but the alternative is worse: death for those needing livers, hearts or lungs; or, for kidney patients, a life on dialysis, which brings an even worse life expectancy and quality of life than a transplanted kidney does.
Schaffer underwent his operation in 2017 and is down to one pill a day – a low dose of anti-rejection drug. The more researchers learned about the symphony of white blood cells that control responses to infections and cancers – and transplanted organs – the more they began to see hope for modifying the body’s immune system.
A number of researchers, including Dr James Markmann and his colleague, Dr Eva Guinan of the Dana-Farber Cancer Institute, chose to focus on cells called regulatory T lymphocytes.
These are rare white blood cells that help the body identify its own cells as not foreign.
The idea is to isolate regulatory T cells from a patient about to have a liver or kidney transplant. Then scientists attempt to grow them in the lab along with cells from the donor.
Then the T cells are infused back to the patient. The process, scientists hope, will teach the immune system to accept the donated organ.
Markmann, working with liver transplant patients, and Dr Joseph Leventhal, working with kidney transplant patients, are starting studies using regulatory T cells.
At Pittsburgh, the plan is to modify a different immune system cell, called regulatory dendritic cells. Like regulatory T cells, they are rare and enable the rest of the immune system to distinguish self from non-self.