29 January 2022 | New Scientist |
9
TWO pig kidneys genetically
engineered to prevent rejection
by the immune system have
been transplanted into a man
who was brain dead as a first
step towards treating patients.
The kidneys weren’t rejected
during the 77 hours that the
experiment, carried out in
the US, lasted.
“This game-changing
moment [is] a major
milestone in the field of
xenotransplantation, which is
arguably the best solution to the
organ shortage crisis,” surgeon
Jayme Locke at the University
of Alabama at Birmingham
said in a statement. The aim
of the study is to pave the way
for a clinical trial, which Locke
hopes will start later this year.
The experiment took place
on 30 September, but the
details were revealed in a paper
published last week (
American
Journal of Transplantation
,
doi. org/hdpw). The kidneys
came from the same line of
genetically modified pigs that
provided the heart transplanted
into David Bennett on 7 January
in a world first. While Bennett
got the pig heart because there
were no other options for him,
the kidney transplant was done
as an initial safety test only.
The recipient, Jim Parsons,
was injured during a motorcycle
race. He was a registered organ
donor, but none of his organs
was suitable for transplantation.
His family gave permission
for his body to be kept alive
on a ventilator so the study
could be done. His own kidneys
were removed and replaced
with the genetically engineered
pig kidneys.
“As a family, we had no doubt
that this is what Jim would
have wanted,” his ex-wife Julie
O’Hara told a press briefing,
standing alongside other
family members.
Locke told the briefing
that, while the idea of testing
therapies in brain-dead people
has been proposed before, her
team is the first to do it. The
Parsons model, as her team
has decided to call it, could be
valuable where animal testing
isn’t sufficient, she said.
Pig organs cannot normally
be transplanted into people
because they are rejected by
the human immune system,
even if the recipient is given
immunosuppressant drugs.
In the pigs created by US firm
Revivicor, four genes have been
switched off, including some
that code for proteins that
provoke an immune response
in humans. The pigs also have
six added human genes.
This work was made possible
by the development of the
CRISPR gene-editing technique,
said Locke. “With that, the
field of xenotransplantation
has exploded,” she said.
The pig kidneys weren’t
rejected during the 77-hour
experiment. “Within 23 minutes,
it began to make urine,” said
Locke, referring to the first of the
two pig kidneys transplanted.
“It’s a remarkable achievement.
We had a beautiful pink kidney,
not one that turned black from
hyperacute rejection.”
However, while the kidneys
produced urine, they didn’t
remove a substance called
creatinine from the blood,
a key measure of normal
kidney function. The team
isn’t sure why this was the
case, but it could be related
to Parsons’s condition.
One potential issue is that
pigs have a lower blood pressure
than people, meaning the blood
vessels in pig kidneys might be
damaged by the higher blood
pressure after transplantation.
But the team saw no indication
of any problems.
Another concern is that
virus genes lurking in the
genomes of pigs might be able
to infect people, but the team
found no sign of this. However,
at least one other company
working on creating pigs
suitable for transplants is
deleting all the viral genes to
ensure this cannot happen.
Locke told the briefing
that although kidney
transplantation is the cure for
chronic kidney disease, most
people die before they can
receive a donor kidney. There
are around 100,000 people
on the waiting list for kidney
transplants in the US, but fewer
than 25,000 such operations are
done each year. “The need still
far exceeds supply,” she said.
“We need a radical solution.”
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