€85million European programme targets novel antibiotics

The growing problem of resistance to antibiotics is very costly, both in human lives and in resources. Uppsala University is now to be a leading actor in a gigantic EU-funded project in which academia, the pharmaceutical industry and the biotechnology industry will collaborate to fast-track the development of new antibiotics.

Over 30 European universities and companies, led by GlaxoSmithKline and Uppsala University, are joining forces in a 6 year programme funded by the Innovative Medicines Initiative (IMI) to develop novel antibiotics against Gram-negative pathogens in a project called ENABLE (European Gram Negative Antibacterial Engine).

The antibiotic crisis

The world faces a growing epidemic of antibiotics resistance, however only two new classes of antibiotics have been brought to the market in the last 30 years. The discovery and development of new antibiotics is essential to maintain medical advances but poses significant scientific, clinical, and financial challenges, particularly for antibiotics active against Gram-negative bacteria (such as E.coli). Such bacteria have effective barriers against drugs, making treatment difficult, resistance likely and development costs and risks high. In addition, any new antibiotics brought to the market would likely be used cautiously to delay the development of resistance, adding an additional financial challenge in recouping the development costs.

Public private route forward In response to such barriers in the development of novel antibiotics, the IMI, a research partnership between the European Commission and major pharmaceutical companies (through EFPIA, the European Federation of Pharmaceutical Industries and Associations), has launched New Drugs for Bad Bugs (ND4BB), a series of projects to target the bottlenecks in the development and effective use of novel antibiotics.

The ENABLE project, the third within the ND4BB series, spans 13 countries and brings together 32 partners with the mission to establish a significant anti-bacterial drug discovery platform for the progression of research programmes through discovery and Phase 1 clinical trials. A preliminary portfolio of programmes will be expanded through open calls outside the consortium to create a full development pipeline, with the ultimate goal to deliver at least one novel anti-bacterial candidate against gram negative infections into Phase 2 clinical trials by 2019.

This joint public and private investment through the IMI reflects the changing nature of drug development for high-risk areas such as antibiotics, and has the mission to mobilise expertise from universities and industry in Europe to meet global challenges. It places Europe at the forefront of collaborative research between industry and academia for health challenges.

"Accelerated efforts like this with the goal of creating an entirely new family of antibiotics are unique. The commitment fills a long-standing gap: Funding for collaboration is needed for the discovery of new antibacterials if we are to be able to cope with infectious diseases in the future, says Anders Karlén", a professor at the Disciplinary Domain of Medicine and Pharmacy at Uppsala University, who is the scientific co-director of the project

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Stroke risk tied to cold, humidity, weather swings

The Associated PressFILE - In this Tuesday, Jan. 21, 2014 file photo, tourists walk through the snow-covered Empty Sky Memorial at Liberty State Park in Jersey City, N.J. Researchers who analyzed local climate trends and hospital records on millions of Americans say there may be a link between weather and the risk for stroke. Cold weather, high humidity and big daily temperature swings brought more stroke hospitalizations. The study by researchers from Yale, Harvard and Duke universities was discussed Wednesday, Feb. 12, 2014 at a stroke conference in San Diego. (AP Photo/Julio Cortez)

      There may be a link between weather and the risk of suffering a stroke, say researchers who analyzed climate trends and hospital records on millions of Americans.

Cold weather, high humidity and big daily temperature swings seem to land more people in the hospital with strokes. As it got warmer, risk fell — 3 percent for every 5 degrees, the study found.

‘‘Maybe some of these meteorological factors serve as a trigger,’’ said Judith Lichtman, a Yale University stroke researcher who led the study. With global climate change and extreme weather like this week’s freak storm in the South, ‘‘this could be increasingly important,’’ she said.

Lichtman and colleagues from Harvard and Duke universities gave results of their study Wednesday at the American Heart Association’s International Stroke Conference in San Diego. It is the largest and most detailed research on this issue.

Each year, about 800,000 Americans have a stroke. Most are due to clots that block a blood vessel to the brain, and high blood pressure is a major risk factor.

Some earlier studies found a seasonal trend to stroke rates, and there are biological reasons to think they are related, said one independent expert, Dr. Andrew Stemer, a neurologist at Georgetown University.

Blood vessels constrict in cold weather, which can raise blood pressure, he said. Extreme weather can trigger a stress reaction by the body, causing it to release substances ‘‘that not only increase the work of the heart’’ but make blood stickier and more likely to clot, Stemer said.

In cold weather ‘‘your body clamps down, there’s cardiovascular stress,’’ said Dr. Larry Goldstein, a Duke stroke specialist who worked on the study.

Conversely, ‘‘high humidity may cause dehydration,’’ which also can raise the risk for clots and raise stress on the body, he said. ‘‘You know how you feel when you’re out in hot, humid weather — you don’t feel so hot.’’

Several of these same researchers published another study earlier this year that looked at stroke deaths from 1999 to 2006 among Medicare patients and found a pattern — higher rates in the winter, lower in summer and a small peak in July.

The new study looked at stroke hospitalizations, not just deaths, in a wider population of adults using a federal database covering all states except Idaho, North Dakota, Delaware and New Hampshire. Researchers also had daily climate data down to the county level from the National Climatic Data Center for 2010 and 2011.

Researchers tracked only strokes caused by clots, not the less common kind caused by a burst or bleeding blood vessel.

Lower temperatures, larger daily temperature changes and higher dew points (humidity) were tied to higher stroke hospitalization rates.

Each 5-degree increase in daily temperature fluctuation (the highest reading minus the lowest one) raised the chance of stroke hospitalization by 6 percent. Each 5-degree rise in the dew point (humidity) raised the risk by 2 percent.

The researchers did not establish a threshold when things were too hot — the point of the study was tracking the general trend, Lichtman said.

The results mean that during extreme weather, friends and relatives should ‘‘keep an eye on people that are at high risk, those who are older,’’ she said.

During stressful weather conditions, ‘‘you want to watch your diet, watch your salt intake, regardless of what the temperatures are,’’ and get enough fluids, said Daniel Lackland, a scientist at Medical University of South Carolina in Charleston.

Goldstein added this advice for people already at cardiovascular risk: ‘‘Stay in air conditioning in the summer and stay heated in the winter,’’ so the weather outside affects you less.

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Novel immune signature 'predicts severity of flu symptoms'

New research recently published in the American Journal of Respiratory and Critical Care Medicine details the discovery of an immune signature that may predict whether patients who have been newly diagnosed with influenza are likely to develop severe symptoms and experience poor outcomes. The research team, led by Investigators from St. Jude Children's Research Hospital in Tennessee, says the findings could also help explain why young children have a higher risk of complications as a result of influenza. For the study, which is still ongoing, the researchers analyzed 84 individuals with influenza that had been acquired from the community. Participants were aged between 3 weeks and 71 years, and 41 of the participants were children aged 23 months or younger. The investigators collected blood, nasal swabs and nasal wash samples from all participants and used these to track their flu infection and immune responses to it for 28 days. The first set of samples was taken once patients sought medical attention for their flu symptoms, and sampling was repeated on days 3, 7, 10 and 28. The investigators carried out similar sampling on 126 volunteers from the households of the flu patients. The researchers also measured the levels of 42 cykotines - small proteins important to cell signaling - in each participant as well as the levels of antibodies that worked against the circulating flu virus.

Children have more aggressive inflammatory response to flu

  the researchers found that both children and adults were able to eliminate the virus from their bodies in 7-10 days. But from analyzing cykotine levels in the blood, nose and sinuses, the researchers found that children had a much more aggressive inflammatory response to influenza compared with adults - a finding the investigators were not expecting to see. Christine Oshansky, of St. Jude Children's Research Hospital and first author of the study, says:
"The fact that the innate immune response was stronger in the airways of children than adults was a surprise. Previous studies using different measures reported that children mounted a weaker immune response."
 The investigators say this finding could explain why infants and toddlers are more likely to suffer severe flu symptoms.

 High levels of three cykotines 'predicts severe flu symptoms' 

Looking into the inflammatory response further, the researchers discovered that high levels of three cykotines at flu diagnosis - MCP-3, interferon alpha 2 (IFNa2) in the nasal and interleukin-10 (IL-10) in the blood - predicted the occurrence of severe flu symptoms later.

Furthermore, the investigators found that patients with high blood levels of IL-10, MCP-3 and interleukin-6 were more likely to be hospitalized as a result of their influenza symptoms.

 According to the researchers, MCP-3 and IFNa2 trigger inflammation, while IL-10 curbs inflammation. They note that high IL-10 levels usually mean that the body is attempting to switch off the inflammatory response.

Additionally, the investigators found that inflammatory cykotine levels were associated with monocytes - white blood cells - that are called to infection sites.

The researchers explain that different types of monocytes can trigger a variety of immune responses through cykotine secretion. They note that although some of these inflammatory responses can be beneficial, some of them could hamper the recovery of the patient. Overall, the investigators say it is clear that new treatments need to be created that target this immune signature. Paul Thomas, of the Department of Immunology at St. Jude Children's Research Hospital and co-author of the study, says:

 "Patients in this study could handle the flu virus and clear it from their lungs in a week to 10 days. The problem for patients with this immune signature is likely the inflammatory environment in their airways created by the innate immune system in response to the virus. Clinically, we need to explore targeted therapies to address this problem separately from efforts to clear the virus." The findings could also explain why the beneficial effects of antiviral drug oseltamivir quickly fade out in the early stages of flu. "

This drug helps get rid of the virus, but these patients do not appear to have a problem with that," adds Thomas. Last year, Medical News Today reported on a study suggesting that the flu virus is able to wipe out the immune system's primary defense against virus re-infection.

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