|| DukeMedNews || Drug Fights Fungus That Attacks AIDS Patients

Today on the Newsline: Duke geneticist Joseph Heitman talks about the discovery of an existing class of drugs used to treat organ transplant recipients that may also help fight a type of fungus that infects and often kills AIDS patients and other people with weakened immune systems.

Background: Researchers at Duke University Medical Center have discovered that an existing class of drugs used to treat organ transplant recipients may also help fight a type of fungus that infects and often kills AIDS patients and other people with weakened immune systems. The researchers said the compounds effectively stopped growth of the fungus in test tube studies. They are now testing the most promising compound in animals afflicted with fungal infections.

In the May 15 issue of the EMBO Journal, geneticist Dr. Joseph Heitman, a Howard Hughes Medical Institute investigator; fungus expert Dr. John Perfect of the division of infectious diseases; and their colleagues identified a trait in the fungus Cryptococcus neoformans that allows it to infect people, and suggested a potential new drug target to stop the infection.

In Cut 1, Heitman says the problems in treating these infections are two-fold. The first is that the immune system itself is compromised, so you don’t have assistance from the immune system in fighting the infection.

Cut 1…inhibit with drugs…:18
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C. neoformans is the leading cause of fungal meningitis, a serious and sometimes deadly infection of the thin membrane that covers and protects the brain. The fungus enters the body through the lungs when a person breathes in its airborne spores. In a healthy person, it is mostly harmless, because the immune system effectively combats the organism. However, in people with suppressed immune systems, the organism can evade the host defense and infect the brain. Between 6 percent and 10 percent of AIDS patients develop this life-threatening infection, the researchers said. In about 40 percent of these patients, it is the first infection they develop when their infection progresses to AIDS.

Heitman says there is a pressing need for new anti-fungal agents against Cryptococcus and other fungi because they are identifying an increase both in the number of cases of serious fungal infection and in strains of fungus resistant to current treatments.

Cut 2…anti-fungal drugs…:17
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Once an infection is established, treatment options are limited. The most effective anti- fungal drug, called fluconazole, requires lifetime therapy in AIDS patients and has side effects such as nausea and kidney disease.

The researchers found the immunosuppressive drugs cyclosporin and FK506, which are used to treat organ transplant recipients, prevent C. neoformans from growing at body temperature, but not at room temperature.