U.K.-based Imutran Ltd. said Tuesday it is poised toconduct the world's first xenotransplant of transgenic pigorgans into humans next year following tests showingthat genetically altered porcine hearts continue to functionin monkeys after 60 days.
In similar experiments in the U.S., the record for primatesurvival with a transgenic pig heart is 30 hours. Howeverunlike Imutran's trials, the U.S. studies did not includeadministration of immunosuppressive drugs to helpprolong survival.
Imutran, of Cambridge, released results in LondonTuesday of studies with 10 cynomolgus monkeys. Themonkeys currently have a median survival of 40 dayswith two still alive 60 days after receiving the pig hearts.
Imutran's officials said the results demonstrate success inovercoming the human immune system's hyperacuterejection of animal organs, one of the major hurdles inxenotransplantation. The transgenic pigs are altered witha human gene designed to create what Imutran's CEOChristopher Samler called a "biomedical illusion,"fooling the human immune system into accepting the pigheart.
The company's researchers were so encouraged by themonkeys' survival that Samler said the first transplant ofa transgenic pig heart into a human will be conductednext year.
"When we set out [on the studies with monkeys]," Samlersaid, "we expected 48 hour survival. Now we're gettingin excess of 60 days."
In addition, Samler said, examination of two monkeysafter 34 and 35 days showed the hearts were intact andbeating normally.
"If it's true, it's encouraging," said John Logan, vicepresident of research and development for Nextran, ofPrinceton, N.J. "It's too early to tell without seeing thedata."
Nextran, which also is conducting studies with transgenicpigs, is a joint venture between DNX Corp., of Raritan,N.J., and Baxter Healthcare Co., a subsidiary of BaxterInternational Inc., of Deerfield, Ill. In July, researchersfrom Nextran and Duke University Medical Center inDurham, N.C., began a clinical trial using transgenic pighearts ex vivo to keep alive human hepatitis patients withliver failure.
Imutran's director of research, David White, is scheduledto present data from the monkey trials at the ThirdInternational Congress for Xenotransplantation, whichwill be held in Boston Sept. 27 to Oct. 1, 1995.
Hyperacute rejection of animal organs by humans occurswhen antibodies alert the complement system, which ispart of the immune system, to attack the foreignsubstance with a series of proteins.
To prevent the onslaught from killing human cells, theimmune system releases other proteins that stymie thecomplement's assault. The earliest of the complementregulating molecules is called decay accelerating factorand the gene expressing that protein is the one Imutranuses to genetically alter pigs so their hearts will not berejected by humans.
In addition to the transgenic pig hearts, Samler said allthe monkeys also received an immunosuppressionregimen, made up mostly of cyclosporin. The drugs wereadministered in levels similar to those that humans wouldreceive.
A control group of monkeys receiving normal pig heartsalong with immunosuppressive drugs lived 55 minutes.
Samler said protocols for next year's clinical trials testingxenotransplant of transgenic pig hearts into humans havenot been completed.
"We have to produce pigs of the right sort and rightspecification," he said, adding that the best mix ofimmunosuppressive drugs has to be determined.
Samler said Imutran also will be examining regulatoryrestrictions for conducting the studies in Europe, the U.S.and Japan. Whereas the FDA in the U.S. is consideringregulations for xenotransplantation, Samler said Europe'sregulatory efforts on the use of transgenic organs are lesswell defined.
"In the U.K. and Europe there's no slot into which it fits,"he said. "It doesn't fit in pharmaceuticals or the devicearea." However, he added governments in a number ofEuropean countries have recognized the potentialproblems and are working to resolve the issues.
As for selecting patients to become the first recipients oftransgenic pig hearts, Samler said those details also mustbe worked out.
In general, he said, "We anticipate patients who either forage or other circumstances were not able to get on awaiting list [for a human heart transplant]."
Imutran, a privately held company, is conducting itsxenotransplantation research with transgenic pigs under acollaboration with Switzerland-based Sandoz Ltd.
In addition to transgenic pig hearts, Samler said, Imutranis exploring the possibility of using genetically alteredporcine lungs and kidneys for human transplant. n
-- Charles Craig
(c) 1997 American Health Consultants. All rights reserved.