The field of xenotransplantation is poised for a significant leap forward as two U.S. companies gear up to commence the world's first clinical trials using pig organs in humans in 2025. This development comes amid increasing urgency from patients facing organ failure and a severe shortage of human donors. The trials will focus on transplanting pig kidneys and hearts, offering a potential lifeline for individuals with life-threatening conditions.
Patient Advocacy Drives Xenotransplantation
Patients are becoming proactive in advocating for xenotransplantation as a viable alternative. Individuals enduring the hardships of dialysis and the uncertainty of long transplant waiting lists are expressing a willingness to participate in research. At a National Kidney Foundation meeting with FDA officials and pig developers in late 2023, patients voiced their desire to explore animal organ transplants, highlighting the dire circumstances they face.
According to Mike Curtis, CEO of eGenesis, the patient's eagerness created "an obligation to try." Dr. Tatsuo Kawai from Massachusetts General Hospital echoed this sentiment, noting that patient advocacy influenced his decision to perform the first gene-edited pig kidney transplant in March 2024.
Early Xenotransplantation Experiments Provide Critical Insights
Prior to the planned clinical trials, several emergency experiments involving gene-edited pig organs have been conducted in humans. While none of the recipients survived longer than two months, these cases offered invaluable lessons. For instance, the detection of a hidden pig virus in the first heart transplant led to the development of more rigorous screening protocols.
Towana Looney, an Alabama woman who received a pig kidney transplant at NYU in late November, represents a potential turning point. According to NYU's Dr. Montgomery, Looney's transplant may serve as a "litmus test" for future trial candidates, as she received the transplant before dialysis caused irreversible damage.
Gene Editing Strategies to Enhance Compatibility
A key challenge in xenotransplantation is preventing the human immune system from rejecting the foreign tissue. Scientists are employing gene-editing techniques to modify pig organs, making them more compatible with the human body. Revivicor, a subsidiary of United Therapeutics, produces pig organs with 10 gene edits, while eGenesis is pursuing a more extensive approach with 69 gene edits.
Dr. Montgomery, however, suggests that "less is more," noting the ease of mass-producing pigs with fewer genetic alterations. Looney's transplant provides an opportunity to assess the impact of additional gene edits.
Balancing Risks and Benefits in Clinical Trials
As clinical trials approach, researchers face the challenge of selecting participants who are sick enough to warrant the experimental procedure but not so ill that their chances of success are compromised. Dr. Silke Niederhaus of the University of Maryland emphasizes the importance of patients understanding their odds of receiving a human kidney before volunteering for xenotransplantation. While acknowledging the risks, she suggests that for older patients whose dialysis is failing, "maybe it's worth taking the risk."
