Mon Jul 29, 5:50 PM ET
By Alison McCook
NEW YORK (Reuters Health) - Researchers have isolated a compound from soil bacteria that may one day offer a safer, more potent way to prevent organ rejection in transplant patients.
The compound is called tautomycetin (TMC) and it acts as a specific inhibitor of the body's T cell-mediated immune response while leaving other components of the immune system untouched.
The body's immune system typically attacks all substances that it deems foreign, which includes viruses, bacteria and new organs. In the case of a transplanted organ, the body launches an immune response mediated by T cells, the key immune cells that normally destroy foreign invaders.
In order to ward off the response of T cells to the foreign organ, transplant recipients typically have to take strong drugs to suppress the immune system, such as cyclosporin. However, these drugs can leave the patient vulnerable to viral illnesses and other infections, and they can cause debilitating side effects, such as liver and kidney toxicity and increased susceptibility to cancer.
Furthermore, in many cases, the treatments do not completely work, and the body rejects the organ anyway.
However, researchers led by Dr. Sang-Kyou Lee of Yonsei University in Korea say TMC may offer stronger protection for patients with fewer side effects. When tested in rats that underwent a heart transplant, those given TMC had comparable survival to animals given cyclosporin and had less damage to other body organs.
"If we find the drug very specific to T cells, that would be a very optimal immune suppressor," Lee told Reuters Health.
Lee added that the drug is currently in the early stages of investigations into whether it will actually work as an anti-rejection therapy. It still remains to be determined if the compound is safe for humans and if so, it could take years before it becomes available.
Reporting their findings in the online Early Edition of the Proceedings of the National Academy of Sciences ( news - web sites), Lee and his team identified TMC by passing thousands of potential compounds through a screening test, designed to measure how well the compounds inhibit T cells.
TMC was the most effective compound, the investigators found. In fact, TMC was able to block the proliferation of T cells when given in a dose that was 100-fold lower than that needed to achieve a similar effect with cyclosporin.
In an interview with Reuters Health, Lee explained that the specificity of TMC results from the fact that it zeros in specifically on active T cells, ensuring that only those cells involved in the rejection of new organs will be targeted. In contrast, other anti-rejection drugs target substances that are ubiquitous in the body, thereby increasing the risk of side effects from the treatment.
In addition, other conditions also involve the activity of T cells against substances the body needs, and TMC may one day be used to treat these conditions, as well, Lee explained. For example, people with multiple sclerosis have T cells that target a protein in the sheath that surrounds nerve cells, thereby damaging nerve cells by exposing them to the outside environment.
The compound also only acts on active T cells, not those at rest, Lee added, so there is no danger of the drug destroying all of these important immune cells in the body. However, the compound could target all of the body's active T cells, which suggests that researchers will have to determine how to administer the drug to a specific region of the body.
There are also concerns that people taking the drug may be at increased
risk of infections. However, with careful monitoring, Lee said that patients
should be safe.
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