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Posts Tagged ‘National Institute of Allergy and Infectious Diseases’

Novartis Cancer Drugs Fight Deadly Ebola Virus in Lab, Researchers Find

April 23, 2012 Leave a comment

Two Novartis AG leukemia drugs, Gleevec and Tasigna, fought the deadly Ebola virus in laboratory experiments, suggesting the products could be used against a disease for which there are no treatments.

The two medicines stopped the release of viral particles from infected cells in lab dishes, a step that in a person may prevent Ebola from spreading in the body and give the immune system time to control it, researchers from the U.S. National Institute of Allergy and Infectious Diseases wrote in the journal Science Translational Medicine today.

There’s no cure and no vaccine for Ebola, a virus that causes high fever, diarrhea, vomiting and internal and external bleeding. Death can ensue within days, and outbreaks in Africa have recorded fatality rates of as much as 90 percent, according to the World Health Organization.

In some forms of leukemia, Gleevec and Tasigna reduce levels of a protein called Bcr-Abl that causes malignant white blood cells to multiply.

The researchers found that Ebola uses a related protein called c-Abl1 tyrosine kinase to regulate its own reproduction. They showed that by blocking c-Abl1, Tasigna may reduce the pathogen’s ability to replicate by as much as 10,000-fold. In addition to showing how the two drugs might be used to treat infected patients, the findings also suggest that new medicines could be developed to target c-Abl1, they wrote.

Gleevec and Tasigna, also known as imatinib and nilotinib, earned Basel, Switzerland-based Novartis a combined $5.45 billion in sales last year. Gleevec is sold as Glivec outside the U.S.

Source: Yahoo! Health

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Cancer Drugs Could Halt Ebola Virus

April 23, 2012 Leave a comment

Some cancer drugs used to treat patients with leukemia may also help stop the Ebola virus and give the body time to control the infection before it turns deadly, US researchers said on Wednesday.

The much-feared Ebola virus emerged in Africa in the 1970s and can incite a hemorrhagic fever which causes a person to bleed to death in up to 90 percent of cases.

While rare, the Ebola virus is considered a potential weapon for bioterrorists because it is so highly contagious, so lethal and has no standard treatment.

But a pair of well-known drugs that have been used to treat leukemia — known as nilotinib and imatinib — appear to have some success in stopping the virus from replicating in human cells.

Lead researcher Mayra Garcia of the US National Institute of Allergy and Infectious Diseases and colleagues reported their finding in Wednesday’s edition of the journal Science Translational Medicine.

By experimenting with human embryonic kidney cells in a lab, they found that a protein called c-Abl1 tyrosine kinase was a key regulator in whether the Ebola virus could replicate or not.

The leukemia drugs work by stopping that protein’s activity. In turn, a viral protein called VP40 stopped the release of viral particles from the infected cells, a process known as filovirus budding.

“Drugs that target filovirus budding would be expected to reduce the spread of infection, giving the immune system time to control the infection,” the study authors wrote.

“Our results suggest that short-term administration of nilotinib or imatinib may be useful in treating Ebola virus infections.”

Imatinib, which is marketed as Gleevec and Glivec, is used to treat chronic myelogenous leukemia in humans, a disease which is caused by dysregulation of c-Abl enzyme.

Nilotinib, also known as Tasigna, has been used in chronic myelogenous leukemia patients who are resistant to imatinib.

Both “have reasonable safety profiles, although some cardiac toxicity has been reported with long-term administration in a small number of patients,” the study added.

According to the UN’s World Health Organization (WHO), about 1,850 cases of Ebola, with some 1,200 deaths, have occurred since 1976.

The virus has a natural reservoir in several species of African fruit bat. Gorillas and other non-human primates are also susceptible to the disease.

Source: Bloomberg

How Dengue Infection Hits Harder the Second Time Around

January 7, 2012 Leave a comment

One of the most vexing challenges in the battle against dengue virus, a mosquito-borne virus responsible for 50-100 million infections every year, is that getting infected once can put people at greater risk for a more severe infection down the road.

The cluster of dark dots near the center of this micrograph shows dengue virus particles. (Credit: CDC)

Now, for the first time, an international team of researchers that includes experts from the University of California, Berkeley, has pulled apart the mechanism behind changing dengue virus genetics and dynamics of host immunity, and they are reporting their findings in the Dec. 21 issue of Science Translational Medicine.

The virus that causes dengue disease is divided into four closely related serotypes (dengue virus 1, 2, 3 and 4), and those serotypes can be further divided into genetic variants, or subtypes.

The researchers showed that a person’s prior immune response to one serotype of dengue virus could influence the interaction with virus subtypes in a subsequent infection. How that interaction plays out could mean the difference between getting a mild fever and going into a fatal circulatory failure from dengue hemorrhagic fever or dengue shock syndrome.

The findings have implications for the efforts to combat a disease that has grown dramatically in recent decades, including the development of a first-ever dengue vaccine.

According to the World Health Organization, dengue disease is now endemic in more than 100 countries around the world, and recent estimates say some 3 billion people — almost half of the world’s population — are at risk.

It was already known that upon a person’s first infection with dengue virus, the immune system reacts normally by creating antibodies to fight the viral invaders. The problem is that those antibodies can then be confused if confronted later with one of the other three types of dengue virus, and as this new study revealed, even different subtypes within the same serotype.

“With the second infection, the antibodies sort of recognize the new type of viruses, but not well enough to clear them from the system,” said study lead author Molly OhAinle, post-doctoral fellow in infectious diseases at UC Berkeley’s School of Public Health. “Instead of neutralizing the viruses, the antibodies bind to them in a way that actually helps them invade the immune system’s other cells and spread.”

The study authors noted that this Trojan horse effect has been shown before, but the new research provides an analysis of the interplay between viral genetics and immune response with unprecedented detail, going beyond the main serotype.

Putting the puzzle pieces together required UC Berkeley’s expertise in immunology and virology, the genome analysis and biostatistical capabilities at the Broad Institute of Harvard University and Massachusetts Institute of Technology, and the epidemiological and clinical field work at Nicaragua’s National Virology Laboratory.

Researchers used data from two independent, Nicaragua-based studies headed by Eva Harris, professor of infectious diseases and vaccinology and director of UC Berkeley’s Center for Global Public Health, and Dr. Angel Balmaseda, director of the National Virology Laboratory in Nicaragua. One was a hospital-based study that examined children admitted to the National Pediatric Reference hospital with dengue between 2005 and 2009. The other was a prospective study that had followed 3,800 children since 2004, with blood samples collected annually.

By following dengue cases in both studies, researchers were able to identify a dramatic increase in severe dengue disease and then sequence the virus across time. They detected genetic changes in the virus that coincided with changes in disease severity, but only in the context of pre-existing immune response to specific dengue virus serotypes.

They found that children who had antibodies to dengue virus 3, which circulated in the region from 1994-1998, were at greater risk for developing severe infections when exposed to subtype 2B of dengue virus 2. They also found that children who had antibodies to dengue virus 1, which circulated from 2002-2005, were also at increased risk of severe disease from exposure to subtype 1 of dengue virus 2 after an initial period of immunity wore off.

“We showed for dengue that both the subtype of virus you get infected with and whether your body has antibodies to another type of virus matter,” said Matthew Henn, director of viral genomics at the Broad Institute. “If you get the wrong combination of the two, you are more likely to get severe disease. This study provides a framework we can utilize to eventually predict which specific virus types will proliferate in different human populations. We lacked a good model for this previously.”

The researchers followed up with tests in the lab to confirm the complex interplay of viral genetics and immune system response.

Harris understands this risk on a personal level. She has been studying dengue in Nicaragua for 24 years, and in 1995, became infected with dengue virus type 3. That puts her at greater risk for a severe reaction should she become exposed to other dengue virus serotypes.

While no vaccine yet exists for dengue, Harris noted that the vaccines currently under development aim to immunize against all types of the virus.

“Our findings have implications for vaccine development and implementation, as the precise genetics of vaccine strains, as well as the timing and serotype sequence of infection prior to and after vaccination, play an important role in determining the outcome of infection,” she said.

Harris added that this study benefited from decades of productive collaboration between U.S. and Nicaraguan researchers. “It was the multi-disciplinary approach we took to analyzing two high-quality studies that allowed us to untangle this very complex phenomenon,” she said.

Funding from the National Institute of General Medical Sciences, the National Institute of Allergy and Infectious Diseases and the Pediatric Dengue Vaccine Initiative provided support for this research.

Story Source:

The above story is reprinted (with editorial adaptations by ScienceDaily staff) from materials provided byUniversity of California – Berkeley. The original article was written by Sarah Yang.

Journal Reference:

M. OhAinle, A. Balmaseda, A. R. Macalalad, Y. Tellez, M. C. Zody, S. Saborio, A. Nunez, N. J. Lennon, B. W. Birren, A. Gordon, M. R. Henn, E. Harris. Dynamics of Dengue Disease Severity Determined by the Interplay Between Viral Genetics and Serotype-Specific Immunity.Science Translational Medicine, 2011; 3 (114): 114ra128 DOI: 10.1126/scitranslmed.3003084