Newspaper article St Louis Post-Dispatch (MO)

Unraveling Aids St. Louis Born-Doctor Is Hopeful of Developing a Drug to Keep the Virus from Reproducing

Newspaper article St Louis Post-Dispatch (MO)

Unraveling Aids St. Louis Born-Doctor Is Hopeful of Developing a Drug to Keep the Virus from Reproducing

Article excerpt

FOR Dr. Michael R. Green and his wife and colleague, Maria Zapp, now comes the interesting part - the first halting step toward something that could rock the world.

Does this former Horton Watkins student, with a doctorate in biochemistry and a medical degree from Washington University, finally have a start on unraveling the AIDS scourge?

He is, of course, extremely cautious when talking about this, although he is hopeful.

"I think we'll have a (test) drug in a patient in a year or two," said Green, whose father, Maurice, is director of the Institute of Molecular Virology at St. Louis University, with a lifetime grant to study cancer viruses.

Green, 39, is a professor of biochemistry and molecular biology at the University of Massachusetts in Worcester and head of its Program in Molecular Medicine. He is one of the scientific founders of ScripTech Pharmaceuticals Inc. of Cambridge, Mass., where he once was an associate professor at Harvard University's medical school.

"The interesting irony is that there will be a lot of pressure on ScripTech to get something in a patient as early as possible," Green added. "There is tremendous political pressure. This is a very political disease."

ScripTech is trying to develop a drug from a category of antibiotics - known to have dangerous side effects - that Green's laboratory found to be successful in inhibiting the reproduction of the AIDS virus. The catch is that neomycin, the most effective of these antibiotics called aminoglycosides, is too poisonous for patients. Green warns AIDS sufferers not to treat themselves with neomycin.

"The major toxic effect causes ringing in the ears and leads to deafness. Ultimately, it will destroy the kidneys. It's always used as a broad-spectrum antibiotic, such as preparing patients for bowel surgery; it cleanses the system from the nose to the rectum."

ScripTech, formed by five venture-capital firms, has enough money to carry it for a couple of years, Barry Weinberg told the trade publication BioWorld Today. He is ScripTech's acting chief operating officer. The hope is to profit from the research of Green and Peter S. Kim, a biochemist from the Massachusetts Institute of Technology.

The focus "is to develop drugs - anti-viral, antibacterial, anti-fungal - that interfere with gene expression and are active in the cell nucleus," Weinberg said.

By telephone from his home in Boylston, Mass., Green said his current work began with his interest in how viruses regulate gene "expression," or that process in which genetic information in DNA is converted into protein.

With Zapp and Seth Stern doing the laboratory "bench work," Green reported the results in the Sept. 24 issue of the prestigious journal Cell.

(Zapp, a biochemist who once was a technician at Washington U., and Green meet in 1986 at a scientific meeting in Cold Spring Harbor, N.Y., "where a famous RNA processing meeting is held annually." She is from Wilkes-Barre, Pa., and has a doctorate from Baylor College of Medicine in Houston.)

While it was known than aminoglycosides kill bacteria by keeping them from making proteins, what these researchers did in the test tube was get these drugs to bond to RNA molecules of the AIDS virus and stop the viral infection in cultured white blood cells. …

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