Protective organ wash engineered
-   +   A-   A+     16/09/2010

Scientists say they have developed a technique that could extend the life of a kidney transplant significantly.

At the moment, fewer than 50% of grafts are still working after a decade inside the patient.

The new approach involves washing the organ in an engineered drug solution during the transfer from the donor to the recipient.

The British Science Festival was told that the solution gives protection to the organ from the immune system.

"It can be expected to almost double the life of a graft," said Professor Steve Sacks from the Medical Research Council (MRC) Centre for Transplantation at King's College London.

The solution limits the action of a part of the immune system, known as the "complement" system, which would normally attack and attempt to destroy cells from any intruder organism, including the cells of a donor organ.

The "complement" system will also support the more general assault on the new organ by the recipient's own blood cells.

Ordinarily, the "complement" response is regulated by protein molecules that sit on the surface of kidney cells, but these molecules are lost in donor organs in the stressful process of transferring the graft into the patient.

To address the problem, the MRC team has engineered in the laboratory a substitute regulator protein it calls Mirococept. As part of this engineering, a "tail" has also been added to ensure the molecule locks down when it is "painted" on to the organ cells.

"The analogy has been used of throwing a bucket of paint against the wall where the paint sticks to the wall, versus a bucket of water which just drains away," said the MRC centre's protein therapeutics director, Dr Richard Smith.

"The synthetic tail is, if you like, the thickening agent in the paint. What it does is to couple to cell membrane; it sticks to the vessel walls and that changes the kidney and gives it more protection against the complement system."

The application of Mirococept is done when the organ is removed from the donor.

Mr Martin Drage, a consultant transplant surgeon at Guy's and St Thomas' hospitals, London, told BBC News: "One of the things that you do when you take a kidney out of a donor is that you have to flush out the blood because it could clot and therefore destroy the kidney - before you put that kidney on ice and transport it to where the recipient is going to be. So as part of the profusion solution to wash out the kidney, the Mirococept is included in the solution as part of the process."

So far, Mirococept has only gone through a safety test to show it will not damage the organ or harm the patient.

The major clinical trial to prove its effectiveness has yet to get under way. But the team says lab studies have been most encouraging, and they would hope to get the treatment introduced in about five years from now if all goes well.

According to NHS Blood and Transplant, more than 7,000 patients are waiting for a kidney transplant in the UK, and only about 3,000 of these are likely to get into an operating theatre during the year.

The gap between those who need a transplant and those who get one is growing by about 4% per year. What is more, about 20% of those on the waiting list are seeking a second transplant because their first graft has failed.

One of the benefits of Mirococept appeared to be its ability to reduce the damage to the organ during transfer, thus increasing the function of the graft in the patient.

"If this work does translate into benefit in clinical practice, which we anticipate it would do - this would mean a grater use of donor organs that might otherwise not be used for transplantation. It would expand the donor pool," Professor Sacks told BBC News.


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