Makana Therapeutics announced on Sept. 4 that the company’s scientists have discovered that pigs contain a fourth gene that when inactivated will greatly reduce the risk of organ rejection in a human recipient.
Makana’s Triple Knockout Pig (“TKO”) is the current foundational genetics used across the field, and is deficient in three genes which drive hyperacute rejection of pig tissue transplanted into humans, Makana said in a release.
In 2012, scientists at Makana discovered the first two of the TKO’s genetic pig modifications and, in 2014, discovered the third. Makana just found a fourth genetic knockout in 2024 required to address the early rejection seen in clinical application of pig organs transplanted into human recipients.
In recent news regarding pig-to-human xenotransplantations, the transplanted organs were rejected by their human recipients within a two-month period, Makana explained. In each of those transplants, “compassionate use” protocols were followed and the transplants were not part of a U.S. Food and Drug Administration (FDA) clinical trial.
“These consistent early losses led Makana to direct its discovery efforts to identify the mechanism responsible for the failures. Every human sample Makana analyzed contained antibodies to the antigen eliminated by Makana’s fourth genetic target,” the company said in a release.
“Our research continues to focus on better understanding the mechanisms of organ rejection in xenotransplantation,” said Makana’s founder Joe Tector, a practicing transplant surgeon at the Miami Transplant Institute. “As a result, we have discovered an additional human immune system response responsible for early xenograft organ failure. We have already created healthy pigs that inactivate the fourth gene to evade this immune response. This is a major breakthrough that will pave the way for clinical success in xenotransplantation.”
Pigs incorporating this knockout were produced last year as part of Makana’s research collaboration with the University of Miami, explained Mark Platt, Makana’s CEO, in a release. The company is preparing to launch its Definitive Preclinical Study in 2025 with plans to conduct a First-in-Human Clinical Trial in kidney xenotransplantation in early 2026 (upon FDA approval).
More detailed results of Makana’s research will be featured in a scientific paper to be published in the coming weeks.
Makana’s first focus will be in the kidney space, Platt said in a release. According to the National Kidney Foundation, there were 786,000 patients in the U.S. living with kidney failure in 2021. In 2022, there were approximately 25,000 kidney transplants performed in the U.S. Still, an estimated 12 people die each day in the U.S. while waiting to receive a kidney transplant. Currently more than 93,000 people are waiting on the U.S. kidney transplant waitlist.
“This has been an enduring challenge for organ transplantation, with the waiting list substantially larger than the supply of donor organs,” Platt said in a release. “Our sole focus is to restore an entirely normal life to every patient with organ failure.”
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