March/April 2022 13GE
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Lone star ticks can transfer
alpha-gal sugar molecules
through their saliva when
they bite you, spurring an
immune system response that
sends a flood of antibodies
to attack the sugar. If your
body overproduces those
antibodies, your immune
system might also attack thealpha-gal found in animal food
products such as pork, beef,
gelatin, and milk. This can lead
to an allergic reaction ranging
from hives to nausea to, in
extreme cases, anaphylaxis.
Alpha-gal syndrome—
unique for its immune system
response to a sugar (most al-
lergic reactions are triggeredby a protein)—has no cure,
but sometimes symptoms
fade over time. Meanwhile,
Revivicor breeds GalSafe pigs
for human consumption in
addition to creating organs
safe for transplants, so meat
lovers with an alpha-gal
allergy could soon enjoy the
occasional slice of bacon.EXPLAINED:
ALPHA-GAL
AND MEAT
ALLERGIES
designed to destroy it. In some people, alpha-gal
antibodies cause an allergic reaction after they con-
sume meat and/or dairy products (see sidebar). For
transplant patients, the presence of alpha-gal in a
transplanted organ can trigger an immune system
response that leads to organ failure.
The researchers performing the pig-to-human
transplant anticipated the possibility of rejection,
says Robert Montgomery, M.D., chair of surgery at
NYU Langone Health and director of the NYU Lan-
gone Transplant Institute. Montgomery and his
team connected the woman’s blood vessels to those
of the pig kidney, clamping the vessels shut to pre-
vent blood f low until the kidney was in place. “Right
before we opened up the clamps, I said to the team, ‘I
don’t know what’s going to happen...but we’re going
to learn something important,’” Montgomery says.
When the team opened the clamps, the woman’s
blood f lowed and filtered normally through the pig’s
kidney. The organ functioned as well at the end of
the experiment as it had in those first few minutes.
“I was pretty blown away,” Montgomery says.
To protect the kidney and the host from rejection
during the transplant, Montgomery and his team
turned to Revivicor, a Virginia-based biotechnol-
ogy company, which produces and breeds “GalSafe”
pigs, animals genetically engineered without the
gene needed to make alpha-gal. Revivicor uses a
method called homologous recombination to pro-
duce the pigs, removing the gene from the nucleus
of a nonreproductive cell and then inserting that
modified nucleus into a female reproductive cell.
Once the reproductive cell develops into an embr yo,
researchers implant it into a “pseudopregnant” sow,
a pig that’s experiencing the physical and behavior
changes of pregnancy but is not actually pregnant.The sow will then give birth to a pig that’s miss-
ing the alpha-gal gene, and that pig can breed with
other GalSafe pigs to produce more pigs without the
alpha-gal gene.
The surgeons transplanted the pig’s thymus in
addition to its kidney. The thymus gland controls
the release of mature T-cells, immune system cells
that fight foreign invaders in the body. It also deletes
T-cells that malfunction and attack the body’s own
tissues. In a pig-to-human transplant, the pig thy-
mus deletes human T-cells that would otherwise
attack the donated pig organs—in this case, the kid-
ney. Including the thymus was an unusual part of the
protocol and is not the clinical standard, says Susan
Quaggin, M.D., chief nephrologist and professor of
medicine at Northwestern University. Typically,
surgeons administer immunosuppressive drugs to
prevent the organ recipient’s immune system from
attacking the new organ. Using the thymus instead
is “exciting and innovative,” she says, but this novel
approach could slow down this procedure’s path to
FDA approval if more testing is required.
The next step will be to test the viability of the
GalSafe kidney in a living human, Montgomery
says. While this procedure didn’t indicate how long
the kidney would keep working in a human, it sug-
gested the pig kidney won’t be immediately rejected,
he says. “I think that’s going to give all of us who are
involved in this field, and the [government] regula-
tors, some increased confidence that it’s going to be
okay, and that we can now make this jump.”
The technology is unlikely to ever fully replace
human kidneys, but after clinical trials and plenty
of follow-up, Montgomery says, genetically modified
pig kidneys will become a viable option for kidney
transplant patients in the next five to 10 years.