Apr 07 2016

Pig Heart Kept Alive in Baboon

xenofunAbout 3,500 heart transplants are performed worldwide each year. This is the standard of care treatment for end stage heart failure. However, more people need hearts than receive them. About half of the recipients of a donor heart have been on the waiting list for more than a year. About a third for more than two years.

In short, there are not enough hearts to go around. Artificial hearts exist, but only as a bridging technology – keeping people alive while on the transplant waiting list. Stem cell therapy looks promising as a treatment for heart failure, but also is years away. Growing hearts is probably decades away.

Genetically modifying animal hearts is probably the option for a human donor heart replacement that is closest to becoming a reality. Recently researchers report that they have made progress along those lines – keeping a pig heart alive in a baboon for over two years.

This technique is called a xenograft, from one species to another. The primary risk of transplantation is rejection; the immune system will recognize the transplanted tissue as foreign and mount an immune attack against it, killing the transplanted tissue.

The more similar the donor and recipient are genetically (the better the match) then the less is the immune response and the lower the chance of rejection. One human can reject another human’s heart. A heart from another species would be out of the question.

Anti-rejection drugs, even for high match transplants, are routine. These are drugs that suppress that part of the immune system which is responsible for attacking the donated organ. These drugs have become quite effective over the years, but are still not perfect, and by themselves would not be enough to accept a xenograft.

The researchers, a team of US and German doctors, have been using a combination of two techniques to enhance the survival of pig hearts transplanted into baboons. They use a combination of anti-rejection drugs, including monoclonal antibodies directed at parts of the immune system. They write:

Our immunomodulatory drug regimen includes induction with anti-thymocyte globulin and αCD20 antibody, followed by maintenance with mycophenolate mofetil and an intensively dosed αCD40 (2C10R4) antibody.

Additionally, the hearts came from a line of pigs that have been genetically modified to express some human proteins:

“…alpha 1-3 galactosyltransferase gene knockout pigs, which express human complement regulatory protein CD46 and human thrombomodulin (GTKO.hCD46.hTBM)…”

They did not replace the baboon’s existing heart, that was kept in and continued to pump blood. They simply added the pig heart and did connect it to blood flow. With these combined techniques of genetic modification and anti-rejection drugs the transplanted pig hearts survived a median of 298 days, with the longest surviving 945 days. Their previous record was 180 and 500 days respectively.

This is an excellent proof of concept, but obviously we are still years away from transplanting pig hearts into humans. The researchers say they will next actually replace the baboon hearts with transplanted pig hearts. I imagine they will also continue to tweak their drug regimen, and perhaps even the genetic modifications in the pig line, to improve survival of the hearts.

I don’t know what the magic number is, but about 50% of heart transplant recipients survive for at least 10 years, so that seems like a reasonable minimum goal. However, xenografts might be used as a bridging technology, keeping people alive for 2-3 years while they are on the human donor waiting list.

New technologies tend to hit the public consciousness 20-30 years before they become a reality. The idea of xenografts has been around for a while. The girl with the baboon heart (Baby Fae) was in 1984, although admittedly I think that was a bit premature. The novel, Pig Heart Boy, was published in 1997. Seriously considering xenografts using genetic modification and powerful new anti-rejection drugs is perhaps a decade old.

I think we are 15-20 years away from such transplants, if all goes well (always a big “if”). Perhaps CRISPR technology will accelerate this a bit, but researchers need a certain amount of minimum time to test out new techniques. You cannot know about 10 year survival for at least 10 years.

Public acceptance of xenografts is another matter. However, I think doctors and their patients and the patient’s families will happily ignore protesters with clever slogans to save lives.

 

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