Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Antipsychotic drugs stop fatal viral infection in brain cells

19.11.2004


Generic antipsychotic drugs can protect brain cells from a virus that causes a fatal nervous system disorder, according to research conducted at Brown University and Case Western Reserve University.



The disorder, called progressive multifocal leukoencephalopathy or PML, affects hundreds of Americans with suppressed immune systems, including kidney transplant recipients, cancer patients undergoing chemotherapy and an estimated 4 percent of people with AIDS.

PML is caused by the JC virus, which destroys the cells that produce the fatty sheath that covers nerve cells. This causes dementia, vision loss, movement and speech impairment, paralysis and coma. The disorder is fast moving and fatal; Many patients die within four months after onset. PML is also on the rise. Due to the AIDS pandemic, incidence of the disorder rose 20-fold in the United States between 1979 and 1994, according to a study conducted by federal researchers.


But a team of scientists, led by Brown virologist Walter Atwood, has found that a handful of antipsychotic drugs can prevent brain cells from becoming infected by the JC virus. The drugs may prove to be an effective, ready-made therapy for PML prevention or treatment. Their results are published in the current issue of Science. "This is very promising," Atwood said. "These are generic drugs we can take off the shelf that may help a lot of people." "It is likely that there are many other drugs with none of the potential side effects of antipsychotic drugs that will also block infection," said co-author Bryan Roth, professor of biochemistry at the Case School of Medicine and director of the National Institute of Mental Health’s Psychoactive Drug Screening Program.

Atwood, an associate professor of medical science in the Department of Molecular Microbiology and Immunology at Brown, has studied the JC virus for more than a decade. The virus is common – anywhere from 70 to 80 percent of adults carry it in a latent form – and it infects certain types of glial cells, which support and protect neurons. It travels to the brain in people with severely weakened immune systems. But scientists didn’t know precisely how it infects those cells. Atwood knew that cellular entry depended on a particular protein, called clathrin, and began to test compounds that would block it.

Atwood tried chlorprozamine, a drug used to control psychotic symptoms such as hallucinations and delusions, and found that it worked. But chlorprozamine can cause serious side effects, such as lowered blood pressure, stiffness and tremors, so Atwood and his team tested seven similar drugs. They found that three others, most notably the antipsychotic clozapine, also prevented infection in human glial cells without troubling side effects.

By pinpointing drugs that block the JC virus, researchers uncovered how the virus operates in the body. The JC virus attaches itself to a receptor on the surface of glial cells, called 5HT2AR, which normally binds with serotonin, a compound that plays an important role in depression and anxiety. That receptor, or cellular "gate," opens and allows the virus to get inside cells.

To be sure that 5HT2AR was the cellular receptor for the virus, Atwood’s team conducted a novel experiment. They took a line of cancer cells that lack 5HT2AR and inserted the receptor gene. They found that these re-engineered cells were now susceptible to infection from the JC virus. Then researchers used the antipsychotic drugs to see if they blocked the virus. They did.

By understanding that the JC virus can be stopped with clozapine and comparable serotonin receptor blocking drugs, Atwood and Roth said new avenues for PML therapy are now open. The antihistamine cyproheptadine, for example, could have the same effect on the virus. "Cyproheptadine has very high affinity for 5-HT2A receptors and is not likely to have many of the side effects associated with drugs like clozapine and chlorpromazine," Roth said.

Atwood is establishing collaborations with several clinical neurology centers to determine whether compounds such as cyproheptadine will, in fact, help prevent or treat PML. Atwood’s team at Brown included Gwendolyn Elphick, a research associate in the Department of Molecular Microbiology and Immunology; William Querbes, Joslynn Jordan, Sylvia Eash and Aisling Dugan, students in the graduate program in pathobiology; and Gretchen Gee, Kate Manley and Megan Stanifer, students in the graduate program in molecular biology, cell biology and biochemistry. Bryan Roth, Anushree Bhatnagar, and Wesley Kroeze from Case Western Reserve University Medical School collaborated with Atwood on the project.

Wendy Lawton | EurekAlert!
Further information:
http://www.brown.edu

More articles from Health and Medicine:

nachricht Satellites, airport visibility readings shed light on troops' exposure to air pollution
09.12.2016 | Veterans Affairs Research Communications

nachricht Oxygen can wake up dormant bacteria for antibiotic attacks
08.12.2016 | Penn State

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: Electron highway inside crystal

Physicists of the University of Würzburg have made an astonishing discovery in a specific type of topological insulators. The effect is due to the structure of the materials used. The researchers have now published their work in the journal Science.

Topological insulators are currently the hot topic in physics according to the newspaper Neue Zürcher Zeitung. Only a few weeks ago, their importance was...

Im Focus: Significantly more productivity in USP lasers

In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.

Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...

Im Focus: Shape matters when light meets atom

Mapping the interaction of a single atom with a single photon may inform design of quantum devices

Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

Researchers identify potentially druggable mutant p53 proteins that promote cancer growth

09.12.2016 | Life Sciences

Scientists produce a new roadmap for guiding development & conservation in the Amazon

09.12.2016 | Ecology, The Environment and Conservation

Satellites, airport visibility readings shed light on troops' exposure to air pollution

09.12.2016 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>