A Genetic Rx for Rejection

[Guest guest]

Biotechnology

A Genetic Rx for Rejection

Gene screens determine transplant treatment

By Jonietz

Organ transplant patients face a catch-22. The powerful drugs that suppress

their immune systems and protect their new organs from rejection can cause

life-threatening side effects, including high blood pressure, susceptibility

to infection and even cancer. Now researchers at the University of

Pittsburgh Medical Center have found a link between a patient's genes and

the chances of rejection that could free many patients from lifelong

dependence on immunosuppressant drugs.

Physicians have long known that certain people are more prone to deadly

rejection episodes than others, regardless of how well a donor organ is

" matched " to their bodies. Studying children who received new hearts, a team

led by immunologist Zeevi has now shown that immune molecules called

cytokines are a likely culprit. Cytokines kick the immune system into high

gear, revving it up to eliminate foreign invaders-helpful if the intruder is

a virus, bad if it's a desperately needed kidney or liver. Zeevi showed that

patients whose bodies produce more of a cytokine called TNF-alpha, but less

of the cytokine IL-10, were most likely to reject their new organs.

Zeevi's team has developed a simple genetic test to determine a patient's

cytokine levels and hopes to forecast which patients can tolerate lower drug

doses. " If their findings hold up, then they could say ahead of time, 'You'

re going to have a liver transplant and you have this genetic profile, so I'

m going to both give you lower immunosuppression and try to wean you from

the drugs altogether,' " says Greenstein, chief scientific officer at

BioTransplant, a town, Mass., company that specializes in

transplantation technology.

To prove the theory, every transplant recipient at Pittsburgh Medical Center

is now given the test-almost 500 patients a year. And Mazariegos, a

transplant surgeon who is working with Zeevi, says that by year's end he

will begin using the genetic screen to select liver transplant patients who

are good candidates for weaning from drug treatment. Initial evidence

indicates that as many as 30 percent could qualify. Zeevi and Mazariegos

predict that profiling transplant patients' cytokine genes will become

standard medical practice in about five years.

Jonietz is working as an editorial intern at Technology Review while

she finishes a master's in science journalism at Boston University.

[Guest guest]

Biotechnology

A Genetic Rx for Rejection

Gene screens determine transplant treatment

By Jonietz

Organ transplant patients face a catch-22. The powerful drugs that suppress

their immune systems and protect their new organs from rejection can cause

life-threatening side effects, including high blood pressure, susceptibility

to infection and even cancer. Now researchers at the University of

Pittsburgh Medical Center have found a link between a patient's genes and

the chances of rejection that could free many patients from lifelong

dependence on immunosuppressant drugs.

Physicians have long known that certain people are more prone to deadly

rejection episodes than others, regardless of how well a donor organ is

" matched " to their bodies. Studying children who received new hearts, a team

led by immunologist Zeevi has now shown that immune molecules called

cytokines are a likely culprit. Cytokines kick the immune system into high

gear, revving it up to eliminate foreign invaders-helpful if the intruder is

a virus, bad if it's a desperately needed kidney or liver. Zeevi showed that

patients whose bodies produce more of a cytokine called TNF-alpha, but less

of the cytokine IL-10, were most likely to reject their new organs.

Zeevi's team has developed a simple genetic test to determine a patient's

cytokine levels and hopes to forecast which patients can tolerate lower drug

doses. " If their findings hold up, then they could say ahead of time, 'You'

re going to have a liver transplant and you have this genetic profile, so I'

m going to both give you lower immunosuppression and try to wean you from

the drugs altogether,' " says Greenstein, chief scientific officer at

BioTransplant, a town, Mass., company that specializes in

transplantation technology.

To prove the theory, every transplant recipient at Pittsburgh Medical Center

is now given the test-almost 500 patients a year. And Mazariegos, a

transplant surgeon who is working with Zeevi, says that by year's end he

will begin using the genetic screen to select liver transplant patients who

are good candidates for weaning from drug treatment. Initial evidence

indicates that as many as 30 percent could qualify. Zeevi and Mazariegos

predict that profiling transplant patients' cytokine genes will become

standard medical practice in about five years.

Jonietz is working as an editorial intern at Technology Review while

she finishes a master's in science journalism at Boston University.