February 15, 2003


 Xenotransplantation efforts march forward

Posted Feb. 1, 2003


Scientists have disabled both copies of a gene in pigs that has stymied researchers' efforts to transplant pig organs into humans. The news, first published online in the journal Science, www.scienceexpress.org, Dec. 19, 2002, brings the goal of xenotransplantation one step closer.

More than 54,000 people in the United States are currently waiting for some type of organ transplant. Because there is no indication that organ donations from people will increase, researchers hope that animal organs can be used to meet the demand.

While some individuals urge caution, worrying that animal diseases could spread to humans, researchers are moving forward, focusing on pigs.

Among the biggest stumbling blocks for researchers are certain galactose sugars, galactosea1,3galactose, which line the walls of pigs' blood vessels. They are also found on the surface of various bacteria and viruses and, as a result, many primates have developed antibodies against them. When a pig organ is transplanted into a primate, antibodies attach to the sugars and activate complement. This so-called hyperacute rejection occurs within minutes of a transplant.

In January 2002, PPL Therapeutics in Blacksburg, Va., announced it had succeeded in disabling one copy of the gene that produces these galactose sugars (see JAVMA, April 15, 2002, page 1129). Now, they have disabled both copies of the gene, using a proprietary gene targeting technology and nuclear transfer.

Four healthy pigs were born at the facility this past July; a fifth pig died shortly after birth of unknown causes. Three additional pigs were born this winter and also are healthy. Tissues from these pigs have, so far, proven to be completely free of the troublesome sugars that cause the hyperacute rejection.

The next step is to test pig organs in primates, and to do so, the company will work collaboratively with the University of Pittsburgh's Thomas E. Starzl Transplant Institute. "We are planning the pig-to-primate transplant studies for mid-2003," said David Ayares, PhD, vice president of research at PPL Therapeutics. The company will first focus on transplanting kidney cells and islets, cells that produce insulin and whose malfunction plays a role in diabetes.