Japanese Antiviral Discovery

A medical professor has found that a combination of two commonly used intravenous drugs completely stops replication of the AIDS virus in the test tubes. The discovery is unknown in the U.S.; this article is the only information so far published in English.

The discoverer believes the combination would probably work as an AIDS treatment, at about a tenth the cost of AZT.
Other physicians contacted by the writer urge caution, however, as the drugs would be dangerous for some patients and may not
be feasible for long-term use. This treatment has never been tried in people. While physicians could easily administer it
today, there are no plans for clinical trials, in Japan or anywhere else.

This writer learned about the discovery from James Palazzolo, a professional Japanese translator with an interest in AIDS. Mr. Palazzolo scans Japanese publications looking for information which may not be available in the U.S. He found
this news in the April 12, 1987 Mainichi Shimbun, one of Japan's major newspapers; later he interviewed the discoverer by telephone. Here is Mr. Palazzolo's translation of the newspaper article, plus notes of the phone interview.


"Dextran Sulfate and Heparin Discovered to Inhibit HIV"

"Assistant Professor Masahiko Itoh (Microbiology) of the Fukushima Prefectural Medical College has discovered that the combination of dextran sulfate, a drug used in the treatment of arteriosclerosis, and heparin, an anti-coagulant, work
synergistically to inhibit the replication of the AIDS virus in the test tube. Professor Itoh added that "these drugs are cheaper and have fewer side effects that AZT, a widely used drug in the U.S. which is effective in prolonging the lives of AIDS patients. Although clinical trials will be necessary, it is hoped that this combination will be effective in prolonging life when used in conjunction with an immune booster."

"Assistant Professor Itoh first noticed that the combination of dextran sulfate and heparin worked to prevent the replication of the herpes virus. Cells (M01 T-4) of the same antigenicity as the lymphocytes which HIV infects were infected with HIV and various concentrations of dextran sulfate and heparin were added. The temperature was maintained close to body temperature at 37 degrees and the cells were cultured for 7 to 10 days. Cells cultured with either dextran sulfate or heparin expanded and were destroyed. In contrast to this, viral replication was completely inhibited when a dextran sulfate concentration of 12.5 micrograms per milliliter and a heparin concentration of 15 micrograms per milliliter were added and the cells continued to live. Furthermore, cell toxicity which indicates possible side effects did not appear, even when concentrations up to 4 milligrams per milliliter were added.

"Assistant Professor Itoh added that "This drug combination has few side effects compared to AZT which
suppresses the production of blood by the bone marrow and I believe this drug combination could cost hundreds of dollars
instead of the thousands of dollars required for AZT."

The newspaper included pictures of the T-cells with and without the treatment.

In Mr. Palazzolo's later phone interview, Assistant Professor Itoh made the following points:

* The heparin stops reverse transcriptase. No one knows what the dextran sulfate does.

* Nothing has been published in English. Nothing has been published in Japanese, except for the above story which was
carried on a major news service there. It will be "quite a while" before the technical paper is finished; he doesn't know
when.

* Of the two kinds of dextran sulfate -- low and high molecular weight -- Itoh suspects that both will work. He could not tell the us which kind he used, because that information must appear first in his paper.

* There are no plans for clinical trials in Japan.

Assistant Professor Itoh is willing to answer letters from U.S. physicians considering clinical use here. He does not speak English, but Mr. Palazzolo has offered to translate.


U.S. Reactions

We spoke with two U.S. physicians while researching this article.

James Campbell, M.D., head of the research committee of the Bay Area Physicians for Human Rights, cautioned about practical problems with the dextran-heparin treatment. "It would have to be administered intravenously long term, as the retrovirus can reactivate. And both medications are anticoagulants, which could cause bleeding problems, especially with this group of patients. Certainly it would be worthwhile to investigate further and find the basis of any antiviral effect."

The other physician also expressed concern about the need to continue intravenous use of the drugs.


Scientific Background

Both dextran and heparin are "polysaccharides" -- chemicals composed of long chains of various sugar molecules.
Scientists are also considering other polysaccharides as possible AIDS treatments, mostly immune modulators; examples are glucan, lentinan (derived from the shiitake mushroom), and possibly other chemicals from different medicinal fungi.

Many different laboratory studies have used both dextran sulfate and heparin together. None of them, so far as we know, looked for an antiviral effect. But the dextran/heparin combination had other results of scientific or clinical relevance. For example, here are the titles of four of over 100 scientific articles published in the last eight years which concern both dextran sulfate and heparin in some way:

* "Thrombin inhibitory activity of heparin cofactor II depends on the molecular weight and sulfate amount of dextran
sulfate."

* "Abolition by dextran sulfate of the heparin-accelerated antithrombin III/thrombin reaction."

* "Inhibition by heparin and dextran sulfate of stimulated rat pancreatic adenylate cyclase."

* "Heparin and dextran sulfate antagonize PGL2 inhibition of platelet aggregation."

These articles, and dozens of others about heparin and dextran together, may give scientists a head start in
understanding the antiviral effect -- and perhaps improving on it. For complete references, call John S. James at 800-TREAT-1-2.