DNX Corp. and Duke University researchers presented dataWednesday on a genetically engineered pig heart transplanted into aprimate in which the onset of hyperacute rejection was delayed for 19hours compared to less than 40 minutes experienced in historicalcontrols. DNX said it was the first such pig-to-primate transplant.The presentation was made at the Strategies for SuccessfulXenotransplantation conference in Washington. Paul Schmitt, presidentand CEO of DNX, told BioWorld the transplant was performed lastweek.Hyperacute rejection occurs in xenotransplantation because thecomplement-inhibition factors on a pig organ do not inhibit humancomplement, leading to quick destruction of the transplanted organ.DNX uses two methods of complement-inhibiting proteins intransgenic pigs. In the direct method, there is expression on theendothelial cells, which line blood vessels, in the organ itself. In thesecond method _ "painting" the organ _ red blood cells are used toproduce the complement proteins, and provide added protection duringthe initial rejection period.The successful experiment was performed in the laboratory of JeffreyPlatt, professor of experimental surgery at Duke University MedicalCenter. The transplant involved a pig's heart with low levels of"painted" proteins to a primate whose immune system was not alteredin any way expected to enhance graft survival.DNX, of Princeton, N.J., has a number of founder pigs expressing highlevels of complement-inhibiting proteins. But it chose to use anotherfor this test."We decided, why not use one of those founders (expressing at lowlevels) for initial experiments?" Schmitt said. "It's a founder that wasmade just to produce proteins in the red blood cells, so it only had theone gene in it. Even at this low level of expression, it lasted 28 timeslonger than we expected."John Logan, DNX's chief scientific officer, said, "With these results inhand, we are optimistic as we progress to our next stage of conductingmore extensive primate organ transplants from pigs with higher levelsof direct expression of complement-inhibiting proteins. We remain ontarget with our plan to begin human experiments in late 1996 at theearliest." n

-- Jim Shrine

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