UW Health, UW-Madison School of Medicine and Public Health: Innovative Clinical Trial Targets Recurrent BK Infection in Kidney Transplant Recipients

MADISON, Wis. – Kidney transplant patients like Tessa Adolph, of Rockford, Illinois, face an age-old problem with protecting their new kidney and their body after a transplant: how to prevent infection while protecting their new kidney from damage or rejection.

In Adolph’s case, the risk came from the BK virus.

At 19, he was diagnosed with Henoch-Schönlein purpura, a rare disease that causes inflammation and bleeding of small blood vessels in organs of the body, including the kidneys. This developed into a condition called IgA nephropathy, or Berger’s disease, which over time can cause kidney scarring and eventual kidney failure, she said.

People with IgA nephropathy produce too many antibodies that the body uses to protect itself from disease-causing pathogens. In most cases, the disease develops over decades, but Adolph’s condition was extremely aggressive and after two years his kidney function had dropped to around 7%. She had to undergo kidney dialysis for seven months while waiting for a kidney transplant.

“We tried a lot of things to treat it, even chemotherapy and I lost all my hair, but in the end I needed a transplant,” she said.

His mother donated a kidney and through a process called paired kidney exchange, Adolph was able to get a new kidney. Then, a new problem appeared, or more precisely, woke up: the BK virus.

The BK virus causes symptoms similar to those of a cold, and most people are infected with this virus at a young age. The human immune system usually fights it, but the virus continues to linger quietly in the body. The immune system usually controls it, but during transplantation, drugs are used to suppress the activity of the immune system to prevent the body from rejecting the transplanted kidney.

Although immunosuppression is necessary to protect the new organ, it comes with a trade-off: dormant viruses like BK can begin to proliferate, according to Dr. Sandesh Parajuli, transplant physician, UW Health and associate professor of medicine, UW School of Medicine and Public Health.

“We walk that balance between preventing infection and causing kidney damage or outright rejection,” he said. “But there just haven’t been a lot of good options to treat the BK reinfection.”

Traditionally, no antiviral drugs have been effective in fighting BK reinfection, and some are even harmful to new kidneys, with little benefit, so Parajuli felt there had to be a better option, he said. declared.

A solution has been made possible by the Advanced Cell Therapy, or PACT, program at UW Health and the UW School of Medicine and Public Health. The program conducts clinical trials examining cytomegalovirus reinfection in bone marrow transplant patients and other cell therapy trials. Parajuli thought a similar route could be attempted with BK.

Earlier this year, he collaborated with PACT to launch a first-of-its-kind Phase 1 trial using T cells – a type of immune system cell – donated by a close relative of Adolph to treat the infection. The T cells used for this procedure are taken from a donor’s blood, and those that specifically target BK are purified for transfusion at the PACT manufacturing lab at the University Hospital.

It takes six hours to prepare the T cells. Once they are ready, they are infused into the patient to treat the infection.

Adolph’s healthcare team had struggled to contain her BK infection despite multiple treatments, and she eventually had to resume antiviral medication, she said. So in March, Adolph decided to become the first person to enroll in the trial, using cells donated by his father.

“I was like, ‘yeah, I’m down,'” she said. “At that time, I was just tired of dealing with these things.”

Like other PACT cell therapies, a significant advantage of these approaches is a very low risk of side effects other than possible injection site irritation, as the treatments use the body’s immune system to fight the virus. , according to Parajuli.

During the five-minute injection, Adolph felt a bit dizzy but experienced no lasting side effects, she said.

The goal of a phase 1 trial is to find out what dose is safe for patients. Establishing how a drug or device works comes in the later testing phases, Parajuli said.

In Adolph’s case, the drug had an initial impact but did not effectively fight the BK infection. However, the Phase 1 data is essential for future studies, and she is always happy to have participated, Adolph said.

“I hope my participation helps someone else down the road,” she said.

Parajuli hopes to enroll 20 patients. Given the hundreds of kidney transplant patients UW Health cares for in a year, there will be no shortage of potential participants, he said.

The trial is free for participants, however, the cost of conducting the trial is significant, he said.

“These are incredibly expensive trials, and we are looking for help in the form of private donations, support for the biotech industry, etc., but the potential for this treatment will allow us to work to make it a reality,” Parajuli said. . “Kidney transplant patients deserve to have another option to treat BK reinfection.”

A taped interview with Parajuli is available, and he and Adolph are available for a limited number of interviews today.