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New Drugs May Combat AIDS

Two Harvard Research Teams Publish Findings

By Alison D. Morantz

Research teams at two Harvard-affiliated hospitals believe they may have found two drugs that fight the Acquired Immune Deficiency Syndrome (AIDS) virus.

In recently published articles, one team said it has tested a substance--known as dideoxycytidine (ddC)--that appears to be more effective and less toxic than AZT, the drug now used to treat the virus. A second team is conducting experiments on a new version of Soluble t4, a drug that slows the spread of the AIDS virus in the body.

Working in affiliation with three other scientists around the country, Assistant Professor of Medicine Robert T. Schooley and his colleagues concluded in an article published this month in the Annals of Internal Medicine that ddC, which in many ways resembles the FDA-approved AZT, deters the replication of the AIDS virus in humans.

Early results suggest that ddC is not only a "more active" anti-viral agents, but that it is less likely than AZT to cause anemia and low white blood cell counts, Schooley said.

But the new drug can, in high dosages, cause nerve damage, skin rashes and mouth ulcers, he said.

"Our goal is to find a dose of ddC high enough to stop the virus from growing, but low enough not to cause nerve damage," Schooley added.

Six weeks ago, Massachusetts General Hospital--where Schooley is based--and three other centers began administering ddC and AZT every other month. Results suggest that the drug may also prove successful as a temporary "substitute" for AZT medication. In this way, Schooley said, the side effects of both can be minimized.

Participants in the MGH study are mostly outpatients. They receive the drug free of charge.

Although the MGH researchers have so far not had to turn anyone away because of inadequate staffing, a strict screening process has eliminated about half of the applicants.

Schooley said the new drug will probably notgarner FDA approval for several more years.

The second team of researchers last weekpublished a study in Nature written byAssociate Professor of Medicine Jerome E. Groopmanand Randal A. Byrn of New England DeaconessHospital.

Sought-After Drug

Although Groopman, Byrn and their colleagueswere not available for comment, Schooley said theDeaconess study involved a drug known as Solublet4 or CD4.

"Right now, the Soluble t4 drug is the mostsought-after drug in the country," said Schooley.

In separate studies, researchers at both MGHand Deaconess have been testing an early versionof the drug on humans for the pastyear-and-a-half. Preliminary results at bothhospitals, he said, have been promising.

The key difference between the studies is thatMGH administers its version of Soluble t4 throughthe muscular system, while Deaconess administersan almost identical brand intravenously.Deaconess' intravenous method seems to fade fromthe bloodstream more quickly, Schooley said.

Both Harvard-affiliated studies, Schooley said,are only in "preliminary" stages of human testingand involve a small number of in-patient subjects.

Last Wednesday, the Deaconess team revealed abrand-new "hybrid" molecule which is slightlylonger than the first-generation Soluble t4 form."They took a piece of a normal human antibodymolecule and hooked it on the drug," saidSchooley.

Early studies of the new version involvinganimals have found that the drug lingers in thebloodstream two times longer than the otherversion

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