Toxin From China May Offer AIDS Hope
A plant toxin that is widely used in China to induce abortions holds promise as a new medicinal approach to AIDS therapy, according to a report in the latest issue of the Proceedings of the National Academy of Sciences.
The medicine, called GLQ223, is a purified preparation of trichosanthin, a protein found in the root of a gourd that is grown in southern China. The root itself is a Chinese herbal remedy that has been used for centuries as a therapy for respiratory complaints, as well as to cause abortions.
In test tube experiments, GLQ223 appears to represent an advance over other forms of AIDS treatments, according to Dr. Michael S. McGrath of San Francisco General Hospital, the leader of the 15-member research team. This is because the protein seems to selectively kill human immune system cells that are infected with the human immunodeficiency virus, the cause of acquired immune deficiency syndrome.
Much Still Unknown
But GLQ223 has yet to be tested as an AIDS therapy in humans--so its ultimate safety and effectiveness will not be known for at least several years. The researchers have also not published animal data on the potential toxic effects of the drug.
The U.S. Food and Drug Administration is reviewing an April 5 application by the drug’s manufacturer, Genelabs Inc. of Redwood City, to begin testing in humans at San Francisco General, an FDA spokesman said.
Leading AIDS organizations said they were encouraged by the new results, which have yet to be independently confirmed. But they issued strong warnings directed at individuals who may now consider importing less-pure formulations of the protein from China for self-administration.
“Absolutely do not bring this in and perform self-experimentation,” Martin Delaney, the co-director of San Francisco-based Project Inform, said of the plant extract, which is injected into the uterus or muscle when used to induce abortions. “There is a group of people who brought it in and some of them hurt themselves pretty badly with it,” he said.
David Corkery, a spokesman for the American Foundation for AIDS Research in New York, said he was aware of about six individuals in Florida who had developed “serious problems” such as blood clots, seizures, strokes and mental deterioration after injecting the plant extract.
Because trichosanthin is a non-human protein, it may also cause serious side-effects even in a highly purified form, such as severe allergic reactions and the production of antibody molecules that could interfere with any potentially beneficial actions.
Like many experimental AIDS drugs and the prescription drug AZT, GLQ223 appears to interfere with the replication of HIV. But the new test tube findings suggest that GLQ223 can also selectively eliminate the virus from key immune system cells, such as T-4 lymphocytes, monocytes and macrophages, without impairing healthy cells.
According to McGrath, the infection of monocytes and macrophages is particularly important in understanding how the AIDS virus weakens the immune system.
HIV does not destroy monocytes and macrophages. Instead these large white blood cells remain chronically infected and survive for years. As a result, McGrath said, they were major reservoirs within the body for HIV infection.
The decision to study the Chinese plant toxin “was (a case of) serendipity,” McGrath said in an interview.
Hin-Wing Yeung of the Chinese University of Hong Kong had been studying trichosanthin and similar plant toxins for years, primarily because of their ability to cause abortions and to treat choriocarcinoma, an unusual tumor that develops from the membranes which surround the fetus. In the process, he discovered other effects of the toxins.
Revealing Conversation
About two years ago, Yeung was visiting San Francisco General and was “interested in talking to someone about AIDS,” McGrath said. He “told me that he had this protein which killed macrophages better than other things and we decided to test it.”
The new laboratory experiments were conducted using white blood cells that had been intentionally infected with the AIDS virus and macrophages that were isolated from HIV-infected individuals.
Using a variety of techniques, the researchers found that GLQ223 could block the multiplication of HIV in cells that had just been exposed to the AIDS virus and cells that were chronically infected.
In another experiment, the researchers exposed blood samples from eight HIV-infected patients to GLQ223 for three hours. They found “essentially complete suppression” of HIV in the macrophages from the majority of donors; the suppression appeared to persist for up to four weeks. By comparison, HIV remained easily detectable in untreated blood samples.
Trichosanthin belongs to a family of plant proteins that interfere with protein synthesis, but it is not known how it works against HIV.
“I do not assume that this material is going to rid the body of all infected cells and (viral particles),” McGrath said. As a result, he speculated that GLQ223 may need to be tested in combination with other AIDS drugs, such as AZT.
In January, McGrath, Yeung and two other researchers received U.S. patent 4,795,739 for the use of trichosanthin, which is obtained from the root of Trichosanthes kirilowii, and morocharin, an extract from the seeds of Momordica charantia, a Chinese bitter melon plant, as experimental HIV therapies.
The patent is jointly held by Genelabs and the University of California. Sandoz Ltd, a Swiss pharmaceutical company, is also involved in developing GLQ223.
