AIDS TREATMENT NEWS Issue # 77, April 21, 1989
John S. James
The reason for the interest is that laboratory studies suggest that compound Q might kill infected macrophages, and eliminate this major reservoir of HIV from the body. No other treatment has been found to do so.
Two good, readily-available articles summarizing information on compound Q were published in The New York Times, April 18, 1989, Medi- cal Sciences section, and Business Week, April 24, 1989, page 29.
For technical background, see the article by Michael S. McGrath and others, "GLQ223: An Inhibitor of Human Immunodeficiency Virus Replication in Acutely and Chronically Infected Cells of Lymphocyte and Mononuclear Phagocyte Lineage," Proceedings of the National Academy of Sciences, USA, April 15, 1989. Also see the United States Patent, number 4,795,739, date of patent January 3, 1989.
The active ingredient in compound Q is a protein called tricho- santhin, which is extracted from the root of a Chinese cucumber, Tri- chosanthes kirilowii. It must be given by injection. This protein is also used in China to induce abortions, and to treat ectopic preg- nancy, hydatidiform moles, and one particular kind of cancer, choriocarcinoma. (For an overview of the Chinese medicinal use of trichosanthin, see Yu Wang and others, "Scientific Evaluation of Tian Hua Fen (THF) -- History, Chemistry, and Application," Pure and Applied Chemistry, volume 58, number 5, pages 789-798, 1986. "Tian Hua Fen" is the name of the herbal preparation from which tricho- santhin, the active ingredient, can be extracted.)
Injecting impure preparations of the protein could cause fatal side effects. In China there are three different different grades of trichosanthin prepared for injection: crude extract, purified extract, and crystalized, which is the highest purity. Only the crystalized form can be used safely; the others cause severe side effects. (Animal tests cited by Wang and others, reference above, showed a lethal dose to be only three times higher than the effective dose for the least pure grade, only six times for the intermediate, so-called "pure" grade, but over 75 times higher than the effective dose for the purest, crystalized grade.) Fortunately it is fairly easy to test for impurities, using a standard chemical technique called gel chromatography, so it should be straightforward to test that a drug claimed to be the "crystalized" grade really is.
We have heard that side effects (of the Chinese "crystalized" grade) can include fever, muscle weakness, and possible electrolyte imbalance, lasting 12 to 18 hours. These problems may not start for about 12 hours. Because of the possibility of electrolyte imbalance, the patient must be monitored by a physician, so that treatment can be given if necessary. Wang and others (reference above) mention 1,042 cases of human use of the crystalized grade, by intra-amniotic or intramuscular injection, in their paper published in 1986. They said there were no significant side effects; a low fever of 37.5 degrees occurred in 79 percent of the cases. (Since there are no side effects of compound Q in animals unless the dose is extremely high, the side effects of the Chinese crystalized version may result from some remaining impurities, or from the intended killing of target cells, which presumably would not occur in animal toxicity tests.)
There may be additional precautions. For example, repeated use could conceivably cause anaphylaxis, although no such problem has been seen in animal tests. We do not know if there is any Chinese experi- ence with repeated use.
This drug may be dangerous, and must not be used without knowledgeable professional supervision.
A story widely reported in the press claims that six people in Florida used a Chinese version of compound Q, and had to be hospital- ized due to side effects. We have heard serious doubts about the truth of this rumor, and have not been able to confirm it.
We plan to publish further reports on compound Q in future
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