Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Antibiotic might fight HIV-induced neurological problems

29.04.2005


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."

Joanna Downer | EurekAlert!
Further information:
http://www.jhmi.edu

More articles from Health and Medicine:

nachricht Cystic fibrosis alters the structure of mucus in airways
29.06.2017 | University of Iowa Health Care

nachricht Mice provide insight into genetics of autism spectrum disorders
28.06.2017 | University of California - Davis

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Making Waves

Computer scientists use wave packet theory to develop realistic, detailed water wave simulations in real time. Their results will be presented at this year’s SIGGRAPH conference.

Think about the last time you were at a lake, river, or the ocean. Remember the ripples of the water, the waves crashing against the rocks, the wake following...

Im Focus: Can we see monkeys from space? Emerging technologies to map biodiversity

An international team of scientists has proposed a new multi-disciplinary approach in which an array of new technologies will allow us to map biodiversity and the risks that wildlife is facing at the scale of whole landscapes. The findings are published in Nature Ecology and Evolution. This international research is led by the Kunming Institute of Zoology from China, University of East Anglia, University of Leicester and the Leibniz Institute for Zoo and Wildlife Research.

Using a combination of satellite and ground data, the team proposes that it is now possible to map biodiversity with an accuracy that has not been previously...

Im Focus: Climate satellite: Tracking methane with robust laser technology

Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.

Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...

Im Focus: How protons move through a fuel cell

Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.

As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...

Im Focus: A unique data centre for cosmological simulations

Scientists from the Excellence Cluster Universe at the Ludwig-Maximilians-Universität Munich have establised "Cosmowebportal", a unique data centre for cosmological simulations located at the Leibniz Supercomputing Centre (LRZ) of the Bavarian Academy of Sciences. The complete results of a series of large hydrodynamical cosmological simulations are available, with data volumes typically exceeding several hundred terabytes. Scientists worldwide can interactively explore these complex simulations via a web interface and directly access the results.

With current telescopes, scientists can observe our Universe’s galaxies and galaxy clusters and their distribution along an invisible cosmic web. From the...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Plants are networkers

19.06.2017 | Event News

Digital Survival Training for Executives

13.06.2017 | Event News

Global Learning Council Summit 2017

13.06.2017 | Event News

 
Latest News

Nanostructures taste the rainbow

29.06.2017 | Physics and Astronomy

New technique unveils 'matrix' inside tissues and tumors

29.06.2017 | Life Sciences

Cystic fibrosis alters the structure of mucus in airways

29.06.2017 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>