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Researchers Identify a Metabolite as a Biomarker of Diabetes Risk

Type 2 diabetes (T2D) is the most common form of diabetes and is associated with many complications. T2D is preventable through weight control and exercise; however, many individuals are unaware that they are at risk and do not change their lifestyle in time to avoid disease.

Study Reveals Much-needed Strategy to Protect Against Deadly Liver Fibrosis

Chronic liver disease is a leading cause of death in the United States, in part because it often causes the formation of harmful scar tissue—a process known as fibrosis. A study published by Cell Press August 15 in the journal Immunity reveals the central role the immune molecule interleukin 33 (IL-33) plays in the formation of liver fibrosis. The findings suggest that drugs targeting this molecule could serve as a new treatment strategy to protect against liver fibrosis.

“Currently, the therapeutic options for liver fibrosis are limited and not curative,” says senior study author Stefan Wirtz of Friedrich-Alexander University Erlangen-Nuremberg. “We identified novel immunological factors that contribute to the development of liver fibrosis, opening up new avenues for the treatment of this serious condition.”

Liver fibrosis refers to the accumulation of harmful deposits of extracellular matrix (ECM) proteins, and it can eventually lead to organ failure. Past studies have suggested that this kind of damage is associated with abnormal immune responses in the liver, but very little was known about the molecules and cells that contribute to fibrosis.

In the new study, Wirtz and his team found that the amount of IL-33 in the blood was higher than normal in patients with liver disease. Following up on this observation, they discovered that injection of IL-33 into mice caused ECM proteins to build up in the liver, whereas mice that were genetically modified to lack IL-33 were largely protected from fibrosis. The researchers went on to identify the immune networks underlying IL-33’s harmful effects and discovered that this molecule activates immune cells called type 2 innate lymphoid cells (ILC2), which had never before been linked to liver disease.

“Our findings reveal IL-33 as a novel biomarker that could potentially lead to early detection of fibrosis in patients, which may be extremely valuable for preventing further damage to the liver,” Wirtz says. “Moreover, the study shows that drugs targeting IL-33 or ILC2 responses could be a promising strategy to protect against fibrosis and chronic liver disease.”

Study: Interleukin-33-Dependent Innate Lymphoid Cells Mediate Hepatic Fibrosis [Immunity]

Source: EurekAlert!

Creighton Awarded $1.44 Million for Bench-to-Bedside Asthma Research

What started as basic cancer research at Creighton University has yielded promising results for diagnosing and treating asthma – and the National Institutes of Health (NIH) agrees, investing nearly $1.5 million in Creighton to find out more.

In a previous prostate cancer study, Yaping Tu, Ph.D., a cancer biologist and associate professor of pharmacology at Creighton University School of Medicine, studied a mouse model that was missing a specific gene, called RGS2; he believed the deleted gene would lead to prostate cancer in the animals. Though the tumors failed to develop, Tu noticed the mice had trouble breathing and were less active, similar to asthma patients. With the help of Creighton’s renowned allergy and asthma researcher Thomas Casale, M.D., professor of medicine and microbiology and immunology and Chief of the Division of Allergy and Immunology, Tu soon determined the animals suffered from airway hyperresponsiveness, or a twitchiness of the airways – a cardinal feature of asthma.

“This finding piqued our interest and made us wonder if there was a connection to human patients with asthma,” says Tu. “In a preliminary study funded by the American Asthma Foundation, we were able to confirm that RGS2 is downregulated in a high percentage of patients with asthma, confirming the possibility that this may be a target for a novel gene therapy in asthma patients.”
Now with a $1.44 million, four-year NIH grant, Tu and collaborators Casale and Peter Abel, Ph.D., professor of pharmacology at Creighton University School of Medicine, will take a bench-to-bedside approach to explore how the gene works in the development of airway hyperresponsiveness and whether it can be used as a diagnostic marker for asthma. Finally, the collaborators will work to develop a therapeutic approach to restore gene function, with the hope of one day applying the research to human trials.

Asthma currently affects more than 25 million Americans. There is not one cause; different patients have different triggers. The one shared trait, however, is airway hypperresponsiveness possibly related to the change to RGS2.

“Our current treatment options are similar to a lock-and-key,” Casale explains. “Each drug on the market is the key to unlock and treat a different symptom or pathway important in causing asthma – and we still haven’t found all of the keys. We still have a lot of work to do, but our findings suggest that therapy targeting RGS2 gene expression might just be the master key to managing a critical component of asthma as a whole.”

Research reported in this press release was supported by the National Heart, Lung and Blood Institute of the National Institutes of Health under award number R01HL116849. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Source: Creighton University

New Research from SRI Points to Biomarker that Could Track Huntington’s Disease Progression

A hallmark of neurodegenerative diseases such as Alzheimer’s, Parkinson’s and Huntington’s is that by the time symptoms appear, significant brain damage has already occurred—and currently there are no treatments that can reverse it. A team of SRI International researchers has demonstrated that measurements of electrical activity in the brains of mouse models of Huntington’s disease could indicate the presence of disease before the onset of major symptoms. The findings, “Longitudinal Analysis of the Electroencephalogram and Sleep Phenotype in the R6/2 Mouse Model of Huntington’s Disease,” are published in the July 2013 issue of the neurology journal Brain, published by Oxford University Press.

SRI researchers led by Stephen Morairty, Ph.D., a director in the Center for Neuroscience in SRI Biosciences, and Simon Fisher, Ph.D., a postdoctoral fellow at SRI, used electroencephalography (EEG), a noninvasive method commonly used in humans, to measure changes in neuronal electrical activity in a mouse model of Huntington’s disease. Identification of significant changes in the EEG prior to the onset of symptoms would add to evidence that the EEG can be used to identify biomarkers to screen for the presence of a neurodegenerative disease. Further research on such potential biomarkers might one day enable the tracking of disease progression in clinical trials and could facilitate drug development.

“EEG signals are composed of different frequency bands such as delta, theta and gamma, much as light is composed of different frequencies that result in the colors we call red, green and blue,” explained Thomas Kilduff, Ph.D., senior director, Center for Neuroscience, SRI Biosciences. “Our research identified abnormalities in all three of these bands in Huntington’s disease mice. Importantly, the activity in the theta and gamma bands slowed as the disease progressed, indicating that we may be tracking the underlying disease process.”

EEG has shown promise as an indicator of underlying brain dysfunction in neurodegenerative diseases, which otherwise occurs surreptitiously until symptoms appear. Until now, most investigations of EEG in patients with neurodegenerative diseases and in animal models of neurodegenerative diseases have shown significant changes in EEG patterns only after disease symptoms occurred.

“Our breakthrough is that we have found an EEG signature that appears to be a biomarker for the presence of disease in this mouse model of Huntington’s disease that can identify early changes in the brain prior to the onset of behavioral symptoms,” said Morairty, the paper’s senior author. “While the current study focused on Huntington’s disease, many neurodegenerative diseases produce changes in the EEG that are associated with the degenerative process. This is the first step in being able to use the EEG to predict both the presence and progression of neurodegenerative diseases.”

Although previous studies have shown there are distinct and extensive changes in EEG patterns in Alzheimer’s and Huntington’s disease patients, researchers are looking for changes that may occur decades before disease onset.

Huntington’s disease is an inherited disorder that causes certain nerve cells in the brain to die, resulting in motor dysfunction, cognitive decline and psychiatric symptoms. It is the only major neurodegenerative disease where the cause is known with certainty: a genetic mutation that produces a change in a protein that is toxic to neurons.

Study: Longitudinal Analysis of the Electroencephalogram and Sleep Phenotype in the R6/2 Mouse Model of Huntington’s Disease

Source: SRI International

No Biomarkers Identified to Assess Potential Health Effects of GMOs

Many people in Europe are critical of genetically modified (GM) food, due to safety concerns. A Eurobarometer survey, published in 2010, revealed that the European public tends to be worried on a “mediate level” about GM food, with people in Austria being particularly concerned. Today, genetically modified maize is cultivated commercially, mainly in Spain and Portugal. Nonetheless, authorised GM Organisms (GMO) may enter the European market as feed for animals or in food products.

Whether such products pose any health threats to consumers, is controversial. “We have to find the best way to evaluate the issue,” says Michelle Epstein, an allergy and immunology clinician from the Medical University of Vienna, Austria. She coordinated a recently completed EU-funded project called GMSAFOOD that aimed at identifying possible biomarkers for indicating adverse health effects of GM food. Such biomarkers could be used for monitoring commercially available GM food or feed.

The European Food Safety Authority EFSA, who plays a fundamental role in assessing the risk of GM crops and derived food and feed in Europe, has included a recommendation for so-called post-market monitoring (PMM) in its Guidance for risk assessment of food and feed from genetically modified plants, published in 2011. This approach is supposed to complement the pre-market toxicological tests. “This [the PMM] is for the unexpected things”, Epstein explains. “Even if you do a lot of testing before placing a product on the market, it is not the public at large you are testing,” she tells youris.com. Some people may have immune diseases or consume certain products at very high levels.

As part of the project, the researchers conducted feeding experiments with pigs, mice, salmon and rats. They fed them with a variety of commercially available GM maize, called MON 810, and a pea containing a pest resistance gene derived from a bean. “We were using the peas because we knew it had effects”, Epstein says. Indeed, a previous study published in 2005 by Australian scientists had shown allergenic responses in mice feeding on the pea.

However, the researchers were not successful in their search for biomarkers. “We didn’t see any health effects”, Epstein comments. Moreover, when looking at the allergenic effect the peas had caused in the original study, the scientists found the same effects in the native bean, implying that the GM pea did not cause the allergic reaction. They attributed this discrepancy to a cross-reaction with a substance called pea lectin and to technical differences between testing laboratories.

The project scientists also developed a machine learning approach to identify potential GMO-associated biomarkers. Data is fed into a mathematical model, which is supposed to find parameters that may serve as biomarkers. “We proposed to the [European Commission] to set up a public repository with all of the project data,” Epstein says. This public database would also allow people from research and industry to include their own data and use the approach for identifying biomarkers for PMM.

Experts doubt the usefulness of PMM, in this case. “In my view, in contrast to the mandatory post-market environmental monitoring, monitoring GM food is questionable,” comments Joachim Schiemann, biosafety expert at the Julius Kühn-Institut, Federal Research Centre for Cultivated Plants, Germany. He considers the pre-market risk assessment of GM food as sufficient in most cases. He argues that uncertainties should be defined prior to introducing a product to the market. “The regulatory authorities have to decide how much uncertainty is acceptable,” Schiemann adds.

Other experts agree. “I am personally very reluctant to consider PMM as a useful tool for risk management of GM food or feed,” Harry Kuiper, retired scientist at Wageningen University, the Netherlands, and former head of the GMO Panel at EFSA, says. He points at various difficulties PMM may face. For example, he believes that it is hard to determine which group to target and how much of a product people actually consume.

“For the GM foods on the market today, there are simply no indications for identification of biomarkers upon exposure of humans or animals,” Kuiper also tells youris.com. “Personally, I would try to solve problems or uncertainties identified with GM food or feed during the pre-market risk assessment”, he adds. However, he believes that future GM food, which may alter the physiological or nutritional status of humans or animals, may provide opportunities for identifying biomarkers.

While she is not opposed to post-market monitoring, Helen Wallace, director of the not-for-profit organisation Genewatch UK recognises that “it is a very hard thing to do”. Instead, “we need more pre-market assessments of GM crops”, Wallace says. In her view, these should include follow-ups of studies, which suggest possible adverse health effects. She also criticises prevalent study designs and the fact that regulators have to rely on commercial studies: “These lack independence and often data isn’t made public by companies.”

Source: Youris.com