Xenografts – here’s where we stand

Surgeon Jayme Locke and immunologist Megan Sykes

David Bennett, the first patient transplanted with a genetically edited pig heart, died on March 8 last year, two months after the surgery, presumably from a latent pig virus (a problem that does not seem hard to solve with more stringent protocols and screening, as Linda Scobie explained to me a few months ago). Since then, experimental transplants have continued in brain-dead patients who had donated their bodies to research. After xenokidneys with a single genetic modification transplanted in late 2021, in the summer of 2022 it was the turn of ten edits xenohearts. The state of the art now is that the potential of the approach still appears high, as does the morale of specialists.

To learn more, I recommend listening to this Nature Biotechnology podcast, featuring a double interview with transplant surgeon Jayme Locke (University of Alabama at Birmingham) and immunologist Megan Sykes (Columbia University). The first question concerns the motivations that led them to engage in xenotransplantation (organ shortage, the resulting equity issues, the need to operate when it is best for the patient rather than if and when a matching human organ becomes available).

Among the issues discussed are the types of genetic modification that will be necessary (it will also depend on the organ), which organs are best suited for xenotransplantation (the heart, because it is “just” a pump), the reasons why donors are pigs and not monkeys (breeding is easy, gestational time short and litters large; furthermore they present less risk of viral transmission, and many people have fewer ethical qualms about using them for medical purposes since they eat them).

The last question concerns the most pressing issue for the future. For Locke, it is to understand whether xenografts will be able to be a destination therapy or will serve as a bridge therapy (perhaps to grant a dialysis-free period thanks to a temporary xenokidney, or to give the patient time to wait for a compatible human organ). But to know how durable is a pig organ transplanted into humans you will need to try and try again.

Sykes says she is optimistic about the destination therapy issue, in the long run. Her concerns in the short term, however, are twofold. The first is how to meet the standards required to get the official green light for clinical trials [the approval for Bennett was unique, on compassionate grounds]. The second is how to keep industry interested in a field that needs funding for both research and clinical trials, must proceed cautiously, and does not promise immediate profits.

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