Mouse model tests AIDS drug efficacy.
Researchers report success in using mice transplanted with human immune cells to test the efficacy of an AIDS drug. The work bolsters hopes that this animal model can help scientists assess the potential of various drugs against the AIDS-causing virus, or HIV.
Investigators currently screen experimental AIDS drugs in cultured human immune cells infected with HIV. Compounds showing promise in the laboratory become candidates for pilot trials to evaluate safety and efficacy in humans.
But because that method can expose volunteers to high levels of potentially dangerous drugs, scientists have sought a small-animal model that could bridge the gap between laboratory culture and human trials, giving them some idea of a drug's potential toxicity. The search remained frustrating until 1988, when several research teams transplanted components of the human immune system into mice--whose own tissues naturally resist HIV infection--and then injected HIV into the mice (SN: 12/24/88, p.404).
In the Feb. 2 SCIENCE, one of those teams reports using zidovudine (AZT), the only federally approved anti-HIV drug, to suppress HIV infection in immunodeficient mice. Led by Joseph M. McCune of SyStemix of Palo Alto, Calif., the group started by transplanting thymus and lymph node tissue from human fetuses into mice born without immune systems.
The researchers injected 40 of these mice with HIV. At the end of a two-week period, a genetic technique called polymerase chain reaction (PCR) showed all 40 mice positive for the virus. The team then took 17 other mice and treated them with zidovudine for 24 hours before injecting them with HIV and for two weeks immediately after. At the end of those two weeks, the researchers removed and tested some of the transplanted human tissue, finding no hint of HIV when they used the PCR. But when they tested the tissue with an even more sensitive technique called in situ hybridization, they found a few cells infected with HIV. After the mice went four more weeks without zidovudine, the PCR showed HIV replication in tissue from each of the 17.
"It is a demonstration that these kinds of models are going to be useful for drug testing," says Donald E. Mosier of the Medical Biology Institute in La Jolla, Calif., who created a similar AIDS model by implanting white blood cells from human adults into immunodeficient mice. Mosier says such models may also help scientists study other viral diseases. His team, for example, has infected mice with Epstein-Barr virus, which in humans can cause a cancer called Burkitt's lymphoma.
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|Date:||Feb 3, 1990|
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