Could organ transplants use a dose of teen hormones?

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Could organ transplants use a dose of teen hormones?

07 January 2006

USING hormones to turn adults into pre-pubescent children may sound

like a bad idea. But it could provide a way to improve the safety of

organ transplants.

At the moment, transplant patients must be placed on powerful

immunosuppressive drugs for the rest of their lives. The drugs

prevent organ rejection, but raise the risk of infections and

cancers. Now Sachs and his colleagues at the Massachusetts

General Hospital in Boston are experimenting on pigs in an attempt

to trick the immune system into tolerating transplanted organs, and

avoid the need for long-term immune suppression.

Sachs hopes to induce immune tolerance by temporarily rejuvenating

the thymus gland, a small organ beneath the breastbone that " primes "

the immune system's T-cells to attack foreign cells without harming

the body's own tissues. Once children reach adolescence, the sex

hormones testosterone and oestrogen start to stunt the thymus, a

process that continues throughout adult life. " It's big and juicy in

childhood, but starts to get fatty and to wither away after

puberty, " says Sachs. " Although it keeps ticking over, it is never

again as active in priming T-cells. "

Sachs's idea is to reboot the thymus by temporarily shutting off the

sex hormones with Lupron, a synthetic version of gonadotropin-

releasing hormone, or GnRH, which is released from the hypothalamus

in the brain and triggers puberty. The hormone is also able to

rejuvenate the thymus, something that Boyd and his

colleagues at Monash University in , Australia, discovered

in experiments on mice.

Once the thymus has been revived, Sachs will transplant a kidney and

give each pig immunosuppressive drugs for a fortnight. During this

period, the idea is that T-cells in the thymus will be exposed to

cells and proteins from the new kidney, which they should be primed

to treat as " self " . After a few months, the Lupron treatment would

be stopped and the pigs would return hormonally to adulthood,

hopefully with the new organ fully tolerated.

Sachs has previously shown that young pigs equivalent in age to 10-

year-old children can tolerate transplanted organs after only two

weeks of immunosuppressive drug therapy. But this is not the case

for adult pigs, or young pigs that have had their thymuses removed

(Transplantation, vol 77, p 979).

" The thymus is big and juicy in childhood, but starts to get fatty

and wither away after puberty, stunted by sex hormones " These results

suggest that the hormonal treatment might work in pigs. But some

immunologists are sceptical that the procedure will work in

people. " When you transplant organs into even small children, they

reject their organs without immunosuppression, just like adults, "

says Maggie Dallman of Imperial College London.

Sachs agrees, but says that while most teenage transplant patients

who stop taking immunosuppressive drugs do reject their new organs,

some do not. " It does show that tolerance can sometimes develop

naturally, " says Sachs. This gives him hope that his hormonal " teen

treatment " will work. He expects to have results from his pig

experiments within a year. If they are positive, he will then seek

approval to run a human trial.

From issue 2533 of New Scientist magazine, 07 January 2006, page 9