Excluding options.
in some severe cases of pandemic influenza H1N1 09, the virus was resistant against all viral compounds, leaving doctors without medicines.
Zhang Xiaowei / Xinhua / Newscom
The 1918 Spanish flu killed up to 40 million people. The swine flu pandemic in 09 killed about 284,000. Now scientists have discovered a substance that could help doctors save lives during future influenza pandemics. Eritoran, a compound being studied as a drug for sepsis, significantly reduces deaths due to influenza in mice. "This could open up a whole new class of anti-influenza drugs," said Michael Osterholm, a flu expert at the Research Center and policies relating to infectious diseases at the University of Minnesota, Twin Cities, which has not participated.
at present, doctors have a single class of compounds available to fight against influenza. the drugs, Tamiflu and Relenza, block neuraminidase, a surface protein that the virus influenza should leave the cell after reproduction. the drugs, taken orally, are to be given soon after infection to be effective, however, and some flu strains have developed resistance against them. some scientists have also questioned the safety and efficacy of compounds, many countries stocks during the H1N1 pandemic of 09. "Basically, if you see the arsenal available today, it is limited and could be blown over night, "said Albert Osterhaus, a virologist at Erasmus MC in Rotterdam, the Netherlands.
Instead of targeting the virus, Stefanie Vogel immunologist at the University of Maryland, Baltimore, tried to interfere with the host immune system. Scientists have long speculated that some cases of severe flu are not the direct result of the virus havoc, but due to a so-called cytokine storm, a catastrophic overactivation of the immune system that leads to many inflammatory substances being released into the whole body, which can lead to multiple organ failure. For example, immune cells and the liquid can accumulate in the lungs, airway blockage. A 08 study cell suggested that the cascade is triggered by the activation of a molecule called Toll-like receptor 4 (TLR4), which normally signals the immune system to the presence of certain bacteria in the body . If these pathogens overwhelm the body, TLR4 is also thought to trigger inflammation of the entire body known as sepsis. For this reason, blocking TLR4 was viewed as a potential treatment for patients suffering from sepsis.
Vogel and colleagues studied eritoran, a compound that blocks TLR4 and is now in clinical trials as sepsis drug. They infected mice with influenza laboratory strain called PR8 and gave half of them eritoran injections for 5 days, starting 2 days after infection. Ninety percent of the untreated mice died, against only 10% of those given the drug. If the treatment was started at 6 days after infection, 33% of the animals survived. The compound also reduced lung damage in cotton rats, a species that does not die from the influenza strain used for the study, the authors report online today in Nature .
"It is an elegant study based on assumption rather bold," says Osterhaus. But the mechanism of the disease in mice could be different from that of man, he said. "This does not disqualify the results, but that means we must be careful." Vogel said she has already submitted a grant to test the compound in ferrets, the most widely used animal influenza studies. "Since eritoran has a very good safety record in people, we hope that our preclinical studies will ultimately support clinical trials in humans for flu and perhaps other diseases that cause disease by a similar mechanism, "she wrote in an e-mail to science NOW.
For Osterholm, the paper adds to the evidence that influenza causes illness by several different mechanisms. Some strains of influenza, such as the one that caused the Spanish flu in 1918, or swine flu in 09, are more likely to cause death by activating the immune system, leading to more deaths in younger age groups he argued. "This is the case it will be demand." Osterholm but also warns that many promising drug candidates fail at later stages. "We will not know if it works until we put in people."
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