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February 01, 2021

FDA approves genetic alteration in pigs

Modification removes allergen, raising potential for medicine and meat production
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A GalSafe pig
A GalSafe pig (Courtesy of United Therapeutics Corp.)

A line of genetically modified pigs gained the federal approvals needed to be sold for medical uses and meat.

The modification, approved by the Food and Drug Administration in December, eliminates detectable amounts of alpha-gal, a sugar molecule, on the surface of pig cells. The sugar is a trigger for a rare allergy, and its removal could provide a new source of drugs, excipients, cosmetics, and meat, an agency announcement states.

Agency documents also indicate tissues from the pigs might provide candidate cells, tissues, or organs for transplantation into human patients. Even for people without a specific alpha-gal allergy, alpha-gal in transplanted animal tissues can cause hyperacute immune responses and at least contributes to transplant rejection.

The FDA regulates genetic modifications as drugs, and the approval applies to a single swine farm that can produce up to 1,000 pigs yearly.

The Virginia-based company that received the approval, Revivicor, develops genetically engineered pigs for use in producing human-use cells, organs, and medical devices, according to company information. The modification in this line of pigs, known as GalSafe pigs, inserts recombinant DNA to disrupt a gene connected with alpha-gal production.

Dewey Steadman, head of investor relations for Revivicor’s parent company, United Therapeutics Corp., provided a statement that the advancement shows the potential to develop porcine products in areas where alpha-gal could cause adverse reactions in patients with alpha-gal syndrome.

“We look forward to working with potential partners in food, drug, and medical device production to potentially bring these products to market,” it states. “This gene edit is just one of ten edits we are currently using in pigs for our preclinical xenotransplantation development program that we hope one day will help address the critical shortage of transplantable organs for humans in need.”

Alpha-gal function unknown

Uri Galili, PhD, is an immunologist and adjunct professor at Rush Medical College in Chicago. He authored the 2017 book “The Natural Anti-Gal Antibody as Foe Turned Friend in Medicine” and a 2019 review article in the American Journal of Physical Anthropology that describes how inactivation of alpha-gal—and the evolution of anti-gal antibodies—helped prevent extinction among Old World primates during epidemics of viruses that contained alpha-gal epitopes. In the late 1980s, he and Bruce Macher, PhD, professor emeritus at the San Francisco State University Department of Chemistry and Biochemistry, discovered alpha-gal epitopes and anti-gal antibodies and identified their reciprocal distribution.

Dr. Galili said research has yet to reveal the biological role of the alpha-gal epitope or explain why it appeared in early mammals more than 125 million years ago. But the genetically engineered GalSafe pigs seem to live normal lives, without the cataracts observed in his and Dr. Macher’s prior research on mice with a knockout gene for alpha-gal production.

The FDA documents indicate agency officials found no animal safety concerns beyond those expected in conventional swine farming.

GalSafe pigs had better-than-average post-weaning survival rates when compared with conventional farms, but the GalSafe herd had higher neonatal and pre-weaning death rates. The report attributes those differences in early death rates, at least in part, to inbreeding among a small GalSafe pig population and high variability among the small numbers of dams and litters evaluated.

Allergy acquired from ticks

Alpha-gal syndrome is an acquired allergy that can occur when certain ticks transmit alpha-gal molecules into a person’s body, triggering an immune response that leads to an allergic reaction, according to FDA documents. Research implicates lone star and blacklegged ticks, according to the Centers for Disease Control and Prevention.

A scientific article published in May 2019 in Frontiers in Immunology indicates researchers identified alpha-gal in the salivary glands and saliva of lone star and blacklegged ticks. As lone star ticks spread from the Southwestern U.S. to the East Coast, increasing numbers of people reported developing allergic reactions after eating red meat or dairy products, the article states.

CDC information indicates those allergic reactions can be deadly and symptoms can occur three to six hours after a meal or other exposure to products containing alpha-gal—including subsequent tick bites. Symptoms can include hives, nausea, vomiting, difficulty breathing, hypotension, dizziness, faintness, and severe stomach pain.

Most reported allergies have occurred among people in the Southeastern U.S., CDC information states.