By studying animals, Johns Hopkins researchers have discovered that the antibiotic Minocycline might help alleviate HIV's negative effects on the brain and central nervous system, problems that can develop even though antiretroviral therapy controls the virus elsewhere in the body.

Five monkeys infected with simian immunodeficiency virus ( SIV ), a very close relative of HIV, and treated with Minocycline had less damage to brain cells, less brain inflammation, and less virus in the central nervous system than six infected monkeys that received no treatment.

These findings have been published in Journal of the American Medical Association.

" In people, antiretroviral treatments do a great job of controlling HIV in blood, but most of the drugs don't cross the blood-brain barrier very well," says Christine Zink, at the Johns Hopkins University School of Medicine. " As a result, even though the infection seems to be controlled, it may still cause damage in the brain. And because people are living with HIV longer than ever, the prevalence of neurological damage is increasing. Currently, there's no drug to treat it directly."

In use for more than 30 years, Minocycline was specifically designed to cross the blood-brain barrier.

Other researchers have reported that this antibiotic can protect brain cells in animal models of other diseases -- multiple sclerosis, amyotrophic lateral sclerosis, Alzheimer's disease, stroke and more. The drug is being tested in early clinical trials for some non-HIV-related conditions.

" Last year we discovered that SIV triggers some of the same biological pathways of cell death and inflammation as these other diseases," says Sheila Barber. " Testing Minocycline in our animal model of HIV infection was really a logical next step."

A multicenter clinical trial is being planned to test whether Minocycline has the same effects in HIV-infected people as it does in SIV-infected monkeys, but it is not expected to start until sometime next year.

" It is too early to recommend minocycline for patients," emphasizes Ned Sacktor, at the Johns Hopkins Bayview Medical Center." One needs to proceed with a clinical research trial first to prove its safety and efficacy against HIV-associated cognitive impairment. "

SIV and HIV both affect the same tissues in the same way and use the same tricks to infect cells and outwit treatments, but SIV infects only non-human primates, and HIV only infects people.
Antiretroviral drugs target and interfere with the viral proteins needed to accomplish this.

In contrast, Minocycline doesn't target the virus or its proteins. While they're still working out the details, the researchers have shown that Minocycline "calms down" as yet undefined biological pathways that involve two specific proteins -- MCP-1 and p38 -- implicated in damage in neurodegenerative diseases.

The MCP-1 protein, when secreted from brain cells under attack from HIV or SIV, attracts infection-fighting cells known as macrophages, which then enter the brain. The influx of these cells contributes to swelling and inflammation known as encephalitis. The other protein, p38, helps trigger a series of events that result in a cell's programmed death, called apoptosis.

Only one of the five treated monkeys showed any signs of encephalitis, and that monkey's condition was deemed mild by a set of standard measures. After the same amount of time -- 84 days after infection -- five of the six untreated monkeys had evidence of moderate or severe encephalitis and much more physical evidence of damage to brain cells, the researchers report.

Source: John Hopkins Medicine, 2005


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