General Competition (July 1995)

Universal Donor Organs for Transplantation

Sponsor: Alexion Pharmaceuticals, Inc.

• Project Performance Period: 9/15/1995 - 9/14/1999
• Total project (est.): $3,203,033.00
• Requested ATP funds: $1,998,564.00

Organ transplants, once a risky, headline-making medical procedure have become almost commonplace. Major advances in transplantation over the past decade have markedly improved the success rates, and transplantation has become the treatment of choice for most patients in the end stages of organ failure. Besides offering patients a significant improvement in quality of life, or indeed, saving that life, organ transplants can be very cost effective. It has been projected that wider use of kidney transplants in lieu of dialysis treatments could save the federal government $2 billion a year. The single biggest roadblock to broader, more effective use of organ transplants is simple--a severe shortage of donor organs. Although public information campaigns, use of "donor cards," and other measures have brought some increase in the supply, the supply comes nowhere near the demand--the current need for organ transplants is conservatively estimated at 90,000 a year for the United States alone. This is likely to remain the case as long as we are restricted to allogeneic (human-to-human) transplants. Xenogeneic transplants--transplants from other animals--are one possible solution. Pigs, for example, have striking similarities to humans in physiology and organ size. In all but the simplest cases (porcine heart valves already are in use for replacing human mitral valves), xenogeneic transplants fail because of an immune system phenomenon called hyperacute rejection (HAR), which causes graft failures within minutes to hours. Alexion Pharmaceuticals proposes a technically challenging approach to this problem--developing transgenic animals that express key human genes to eliminate the HAR response. Their multidisciplinary research plan will include innovative techniques in molecular biology, immunology, cell biology, enzymology, and transgenic technology to develop transgenic pigs that express both a novel human chimeric complement inhibitor and a human blood group enzyme. Together, these two proteins should suppress or eliminate HAR response, removing a critical obstacle to widespread use of xenogeneic transplants.

For project information:

Dr. Leonard Bell, (203) 776-1790

ATP Project Manager

Mrunal Chapekar, (301) 975-6846
mrunal.chapekar@nist.gov