Novel Approach to Organ Transplantation Allows Patients to Wean Off Anti-Rejection Drugs

A novel approach to organ transplantation has shown promising results, enabling patients to wean off anti-rejection drugs after two years, according to findings from a phase 3 clinical trial presented on Monday.

The Role of Immunosuppressants

Immunosuppressants are crucial for transplant recipients, as they prevent the immune system from attacking the transplanted organ. However, these drugs come with severe side effects, including potential harm to the donated organ and an increased risk of infection and cancer. Furthermore, these medications must be taken for life.

“The holy grail of organ transplantation is achieving tolerance,” said Dr. Dorry Segev, a transplant surgeon at NYU Langone Health in New York City. Tolerance refers to the body's ability to accept a transplanted organ without the need for lifelong immunosuppressive drugs.

The Clinical Trial

The phase 3 trial involved using stem cells taken from the organ donor to help transplant recipients gradually stop taking anti-rejection drugs. The trial, presented at the American Transplant Congress in Philadelphia, found that after two years, 16 out of 19 patients could discontinue their anti-rejection medications entirely. The other three patients had to resume the drugs due to either a rejection episode or deteriorating kidney function.

The trial was funded by biotechnology company Medeor Therapeutics and centered around MDR-101, a stem cell therapy derived from the organ donor. The findings have not yet been published in a peer-reviewed journal.

Expert Opinions

“These are excellent results,” said Dr. Jeffrey Veale, a urologist at UCLA Health specializing in kidney transplantation. He noted that a majority of the patients maintained drug-free status for two years and experienced significant improvements in their quality of life.

Kidneys are the most commonly transplanted organs in the United States, with around 25,000 kidney transplants performed annually. However, approximately 10% are repeat procedures due to kidney failure caused by anti-rejection drugs. Veale explained that if patients could avoid these medications, the transplanted kidneys might last a lifetime, reducing the need for repeat transplants and expanding the pool of available organs.

Case Study: Alex Hernandez

Alex Hernandez, a 27-year-old Milwaukee resident, received a kidney transplant and stem cells from his sister as part of the trial. Born with vesicoureteral reflux, Hernandez’s kidneys were severely damaged, leading to dialysis in college.

In preparation for the stem cells, Hernandez underwent radiation therapy to temporarily suppress his immune system, allowing the stem cells to be accepted. Eleven days post-surgery, the new cells mixed with Hernandez’s immune system, creating a hybrid known as “mixed chimerism.” This process prevents the body from rejecting the new kidney, enabling patients to stop taking immunosuppressant drugs.

“The stem cells basically reprogram your immune system, telling them to recognize that this donor kidney coming in is actually going to be part of your own,” said Dr. Sanjeev Akkina, medical director of the kidney transplant program at Loyola Medicine in suburban Chicago and one of the researchers involved in the trial.

Life-Changing Results

For Hernandez, now 30 and starting his second year of dental school at Marquette University, the results have been transformative. His surgery took place in 2021, and he was completely off anti-rejection drugs by the end of that year. “I had to carry this pill container labeled Monday, Tuesday, Wednesday, Thursday, Friday,” he said. “It’s empty now.”

Future Directions and Challenges

While the results are a significant step forward, Dr. Segev emphasized that further research is needed to apply this approach to a broader range of patients, including those who do not receive organs from closely matched siblings.

Veale also highlighted the logistical challenges of the current approach, which requires the transplant and stem cell donation to occur within a two-week period. His research focuses on extending the time between the organ transplant and the stem cell transplant, showing success in weaning patients off drugs as many as five years post-transplant.

Broader Applications

Doctors hope this approach could eventually apply to other types of organ transplants beyond the kidney. “As we understand how chimerism occurs and what we can do to successfully achieve chimerism, we would be able to apply that to any solid organ transplant,” Segev said.

Implications for Transplant Medicine

This breakthrough could significantly alter the landscape of transplant medicine. By eliminating the need for lifelong immunosuppressant drugs, patients would not only avoid the severe side effects but also enhance the longevity and functionality of the transplanted organs. The success of this trial could pave the way for similar strategies in heart, liver, and lung transplants.

Ongoing Research and Future Trials

Further studies are necessary to validate these findings and expand the application of this approach to a broader population. Future trials will aim to include patients with less closely matched donors and investigate the long-term outcomes of those who have successfully weaned off anti-rejection drugs.

Conclusion

This groundbreaking approach to organ transplantation holds the potential to revolutionize post-transplant care by eliminating the need for lifelong immunosuppressant drugs, improving the quality of life for transplant recipients, and ensuring longer-lasting organ function. Continued research and trials will be essential in making this a viable option for a wider range of patients and transplant types.