Navigation Links
Antibiotic might fight HIV-induced neurological problems

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, the researchers report in the April 27 issue of the 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, D.V.M., Ph.D., professor of comparative medicine 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, the biological "wall" that limits what can pass from the blood into the brain. 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, Ph.D., assistant professor of comparative medicine. "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, M.D., an associate professor of neurology at the Johns Hopkins Bayview Medical Center who wasn't involved with the current study, but who is one of the physicians planning the clinical trial. "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.

"The infection in the animal model is predictable and aggressive, so we can get meaningful data by studying fewer animals," says Zink, who was on the team that developed the model about six years ago. "It's a really demanding test of a potential treatment for HIV."

The animal model has already helped improve understanding of how HIV might affect the brain, and this is the first time it's been used to test a potential treatment. Studies with the animals are augmented by laboratory experiments with cells to clarify observations.

Notably, these laboratory experiments have shown that minocycline somehow suppresses replication of HIV and SIV in macrophages -- the immune cells recruited to the brain during HIV infection -- and lymphocytes -- immune cells that carry "sleeping" HIV and SIV even when antiretroviral treatment is effective.

"If this preliminary observation holds up, minocycline could be really important for treating HIV infection in developing countries where access to traditional antiretroviral drugs is very limited," says Zink. "Most of the 40 million people with HIV infection live in these countries."


'"/>

Source:Johns Hopkins


Related biology news :

1. Antibiotic Resistant Bacterium Uses Sonar-like Strategy to “See?Enemies or Prey
2. New Drugs For Bad Bugs: UF Approach Could Bolster Antibiotic Arsenal
3. To Stop Evolution: New Way Of Fighting Antibiotic Resistance Demonstrated By Scripps Scientists
4. Chemical Engineer Kao Explores Antibiotic Synthesis With DNA Chips
5. Use of Antibiotics for Acne May Increase Risk of Common Illness
6. Large-scale Computer Simulations Reveal New Insights Into Antibiotic Resistance
7. Antibiotic treats lymphoma of the eye
8. Antibiotic inhibits cancer gene activity
9. Newly discovered pathway might help in design of cancer drugs
10. Compound might defeat African sleeping sickness, clinical trial beginning this month
11. Stem cells electric abilities might help their safe clinical use
Post Your Comments:
*Name:
*Comment:
*Email:


(Date:8/21/2018)... ... August 21, 2018 , ... Whether it be ... is dedicated to offering customers a successful experience. When browsing the new ... transition between products, with relevant details such as technical manuals, application notes, and ...
(Date:8/17/2018)... ... August 16, 2018 , ... With increasing safety requirements, and ... research projects, are presenting multiple challenges. To be successful in such a competitive environment, ... different aspects of the multiple tasks needed to develop a new drug or to ...
(Date:8/17/2018)... , ... August 16, 2018 , ... ... world’s first private cord blood bank to separate and store stem cells in ... Center, and Brian Sheehy, M.D. M.A. C.F.A., Founder and Managing Partner IsZo Capital, ...
Breaking Biology News(10 mins):
(Date:8/29/2018)... ... 2018 , ... LabRoots , the leading provider of interactive virtual events ... the launch of a new gamification feature, allowing users to earn points by participating ... most popular shirts. , Throughout each month, LabRoots users will earn points by building ...
(Date:8/23/2018)... ... August 22, 2018 , ... ... Android on September 1st, making it the first fully-featured app for electronic data ... devices. Combined, iOS and Android constitute 99 percent of the market share for ...
(Date:8/17/2018)... ... August 16, 2018 , ... The opening of the new Titusville ... Technical Services in 2016. Chemko had a well established local presence, servicing the Space ... on projects such as the ongoing work at the Mobile Launch Platform (MLP) in ...
(Date:8/14/2018)... ... August 13, 2018 , ... Labconco Corporation manufactures laboratory ... cabinets. In addition, Labconco produces other lab equipment, such as glassware washers and ... quality and consistency in design and manufacturing. , Through this webinar, which ...
Breaking Biology Technology: