Syndicate content

LNA-Based Compounds Can Inhibit Entire Disease-Associated MicroRNA Families

A study published online on March 20, 2011, in Nature Genetics demonstrates that tiny locked nucleic acid (LNA)-based compounds developed by Santaris Pharma A/S can inhibit entire disease-associated microRNA families. This provides a potential new approach for treating a variety of diseases including cancer, viral infections, cardiovascular and muscle diseases. Santaris Pharma A/S, a clinical-stage biopharmaceutical company focused on the research and development of mRNA and microRNA targeted therapies, developed the tiny LNA-based compounds, which are 8-mer LNA oligonucleotides, using its proprietary LNA Drug Platform. The high affinity and target specificity of tiny LNA-based compounds enabled functional inhibition of both single microRNAs and entire microRNA families in a range of tissues in vivo without off-target effects. MicroRNAs have emerged as an important class of small regulatory RNAs encoded in the genome. They act to control the expression of sets of genes and entire pathways and are thus thought of as master regulators of gene expression associated with many diseases. Because they dictate the expression of fundamental regulatory pathways, microRNAs represent potential drug targets in the treatment of many disease processes. "Using tiny LNA-based compounds to successfully inhibit entire disease-associated microRNA families provides a new range of opportunities to develop novel microRNA-targeted drugs for both in-house drug discovery programs, as well as with our partners," said Dr. Henrik Ørum, Vice President and Chief Scientific Officer of Santaris Pharma A/S.

Berkeley Scientists Discuss Systems Biology Advances in Review Issue of Cell

Dr. Adam Arkin, director of the Physical Biosciences Division of the U.S. Department of Energy (DOE)’s Lawrence Berkeley National Laboratory and a leading computational biologist, is the corresponding author of an essay in the March 18, 2011 issue of Cell which describes in detail key technologies and insights that are advancing systems biology research. The paper is titled “Network News: Innovations in 21st Century Systems Biology.” Co-authoring the article is Dr. David Schaffer, a chemical engineer with Berkeley Lab’s Physical Biosciences Division. Both Drs. Arkin and Schaffer also hold appointments with the University of California (UC) Berkeley. The Cell issue is devoted to reviews of systems biology. “System biology aims to understand how individual elements of the cell generate behaviors that allow survival in changeable environments, and collective cellular organization into structured communities,” Dr. Arkin says. “Ultimately, these cellular networks assemble into larger population networks to form large-scale ecologies and thinking machines, such as humans.” In their essay, Drs. Arkin and Schaffer argue that the ideas behind systems biology originated more than a century ago and that the field should be viewed as “a mature synthesis of thought about the implications of biological structure and its dynamic organization.” Research into the evolution, architecture, and function of cells and cellular networks in combination with ever expanding computational power has led to predictive genome-scale regulatory and metabolic models of organisms. Today systems biology is ready to “bridge the gap between correlative analysis and mechanistic insights” that can transform biology from a descriptive science to an engineering science.

New Strategy for Extending Useful Life of Antibiotics

A team of scientists from the University of Oxford, U.K., has devised a new strategy that could one day slow, possibly even prevent, the spread of drug-resistant bacteria. In a new research report published in the March 2011 issue of GENETICS, the scientists show that bacterial gene mutations that lead to drug resistance come at a biological cost not borne by nonresistant strains. They speculate that by altering the bacterial environment in such a way to make these costs too great to bear, drug-resistant strains would eventually be unable to compete with their nonresistant neighbors and die off. "Bacteria have evolved resistance to every major class of antibiotics, and new antibiotics are being developed very slowly; prolonging the effectiveness of existing drugs is therefore crucial for our ability to treat infections," said Dr. Alex Hall, a researcher involved in the work from the Department of Zoology at the University of Oxford. "Our study shows that concepts and tools from evolutionary biology and genetics can give us a boost in this area by identifying novel ways to control the spread of resistance." The research team measured the growth rates of resistant and susceptible Pseudomonas aeruginosa bacteria in a wide range of laboratory conditions. They found that antibiotic resistance has a cost to bacteria, and this cost can be eliminated by adding chemical inhibitors of the enzyme responsible for resistance to the drug. Leveling the playing field increased the ability of resistant bacteria to compete effectively against sensitive strains in the absence of antibiotics. Given that the cost of drug resistance plays an important role in preventing the spread of resistant bacteria, manipulating the cost of resistance may make it possible to prevent resistant bacteria from persisting after the conclusion of antibiotic treatment.

New Blood Analysis Chip Could Yield Diagnoses in Minutes

A major milestone in microfluidics could soon lead to stand-alone, self-powered chips that can diagnose diseases within minutes. A new device, developed by an international team of researchers from the University of California, Berkeley, Dublin City University in Ireland, and Universidad de Valparaíso Chile, is able to process whole blood samples without the use of external tubing and extra components. The researchers have dubbed the device SIMBAS, which stands for Self-powered Integrated Microfluidic Blood Analysis System. The report on SIMBAS was featured as the cover story of the March 7, 2011 issue of the peer-reviewed journal Lab on a Chip. “The dream of a true lab-on-a-chip has been around for a while, but most systems developed thus far have not been truly autonomous,” said Dr. Ivan Dimov, UC Berkeley post-doctoral researcher in bioengineering and co-lead author of the study. “By the time you add tubing and sample prep setup components required to make previous chips function, they lose their characteristic of being small, portable and cheap. In our device, there are no external connections or tubing required, so this can truly become a point-of-care system.” Dr. Dimov works in the lab of the study’s principal investigator, Dr. Luke Lee, UC Berkeley professor of bioengineering and co-director of the Berkeley Sensor and Actuator Center. “This is a very important development for global healthcare diagnostics,” said Dr. Lee. “Field workers would be able to use this device to detect diseases such as HIV or tuberculosis in a matter of minutes. The fact that we reduced the complexity of the biochip and used plastic components makes it much easier to manufacture in high volume at low cost.

Llama Antibodies Provide Clues to Novel Treatment of Virulent Hospital Infection

Clostridium difficile is a health problem that affects hundreds of thousands of patients and costs $10 billion to $20 billion every year in North America. Researchers from the University of Calgary and the National Research Council of Canada and colleagues say they are gaining a deeper understanding of this disease and are closer to developing a novel treatment using antibodies from llamas. "We have found that relatively simple antibodies can interfere with the disease-causing toxins from C. difficile," said paper co-author Dr. Kenneth Ng, an associate professor of biological sciences at the University of Calgary and principal investigator of the Alberta Ingenuity Centre for Carbohydrate Science. "This discovery moves us a step closer to understanding how to neutralize the toxins and to create novel treatments for the disease." His research is part of a paper published in the March 18, 2011 issue of the Journal of Biological Chemistry. Approximately two percent of all patients admitted to hospital may be infected by C. difficile, which thrives when healthy bacteria in the gut are weakened by antibiotics, thus allowing spores from Clostridium to germinate and colonize the large intestine. "This research is significant because C. difficile is an increasing heath care problem and many people may experience multiple infections," said Dr. Glen Armstrong, head of the Department of Microbiology, Immunology, and Infectious Diseases in the Faculty of Medicine at the University of Calgary. "The current treatments are becoming less effective and C. difficile is developing resistance to conventional antibiotics. This research promises to provide a much-needed alternate treatment option that will overcome the failings of conventional antibiotics." C.

Protein Is Promising Candidate for New TB Vaccine

Scientists have discovered a protein secreted by tuberculosis (TB) bacteria that could be a promising new vaccine candidate, they report online on March 18, 2011, in PNAS. The protein could also be used to improve diagnosis of TB. TB is caused by the bacterium Mycobacterium tuberculosis (MTB), which infects the lungs and spreads through the air as a result of coughing. There are 9 million new cases of TB each year, killing 4,700 people a day worldwide. BCG, an attenuated mycobacterial strain, is the only available vaccine but it is of limited effectiveness in protecting against TB. BCG derives from the Mycobacterium bovis bacterium, which infects cattle and is closely related to MTB. Vaccines work by stimulating the immune system to retain a memory of particular molecules from a microbe that will trigger a rapid immune response if the microbe is encountered later. The best candidates for vaccines are those that trigger the strongest response from the immune system. In the new study, scientists identified a protein, called EspC, that triggers a stronger immune response in people infected with the TB bacterium than any other known molecule. This protein is secreted by the TB bacterium but not by the BCG vaccine. As a result, the BCG vaccine does not induce an immune response to this protein, so deploying it as a new TB vaccine would provide additive immunity over and above that provided by BCG. The protein could also be useful as a diagnostic tool, because an immune response to it is seen in TB-infected people, but not in non-infected people who have had a BCG vaccine. Detecting immune responses to it would distinguish BCG-vaccinated people from TB-infected people, which the currently-used tuberculin skin prick test (the Mantoux test) is unable to do.

Scientists Show Enzyme Family Plays Key Role in Cell Motility

Researchers at Albert Einstein College of Medicine of Yeshiva University and colleagues have discovered that members of an enzyme family found in humans and throughout the plant and animal kingdoms play a crucial role in regulating cell motility. Their findings suggest an entirely new strategy for treating conditions ranging from diabetic ulcers to metastatic cancer. Dr. David Sharp, associate professor of physiology & biophysics, was the senior author of the study, which was published online on March 6, 2011, in Nature Cell Biology. "Cells in our bodies are in constant motion, migrating from their birth sites to distant targets," said Dr. Sharp. "Cellular movement builds our tissues and organs and underlies key functions such as the immune response and wound healing. But uncontrolled cell migration can lead to devastating problems including mental retardation, vascular disease, and metastatic cancer." Dr. Sharp and his colleagues found that certain members of an enzyme family known as katanins concentrate at the outer edge of non-dividing cells where they break up microtubules – dynamic intracellular polymers that regulate cell movement by controlling the formation of protrusions called lamellipodia. When Dr. Sharp's team treated motile cells of the fruit fly Drosophila with a drug that inhibited katanin production, the treated cells moved significantly faster than control cells and with a striking increase in high-velocity movements, indicating that katanin prevents cells from moving too rapidly or in an uncontrolled manner. The researchers observed similar effects with katanin when they examined human cells. "Our study opens up a new avenue for developing therapeutic agents for treating wounds – burns and diabetic ulcers, for example – as well as metastatic disease," added Dr. Sharp.

New Research Tool Targets MicroRNA Expression

A new research tool for studying microRNA expression in zebrafish will help researchers analyze the effects of microRNA (miRNA) on the early development of this model organism and better understand developmental and disease mechanisms in humans, as described in Zebrafish, a peer-reviewed journal published by Mary Ann Liebert, Inc. The article is available free online ahead of print. Researchers from University of Oregon (Eugene) have developed a novel, cost-effective method for measuring the expression of miRNAs in specific tissues in developing zebrafish embryos. miRNAs play an important role in regulating embryonic development. They are difficult to detect because they are very short strands of oligonucleotide and are often present in cells at low levels. Drs. Xinjun He, Yi-Lin Yan, April DeLaurier, and John Postlethwait describe the efficient technique they devised using digoxigenin-labeled riboprobes (oligonucleotide-based probe sequences capable of binding to a complementary miRNA sequence) in in situ hybridization (ISH) experiments. "This is a terrific new addition to the zebrafish toolbox, opening the door to an array of new experiments focused on the biology of non-coding RNAs using this superb model system," said Dr. Stephen Ekker, Editor-in-Chief of Zebrafish and Professor of Medicine at the Mayo Clinic, Rochester, Minnesota. [Press release] [Zebrafish abstract]

New Clinical Guidelines on Diagnosis and Management of Idiopathic Pulmonary Fibrosis

The American Thoracic Society has released new official clinical guidelines on the diagnosis and management of idiopathic pulmonary fibrosis (IPF). The statement replaces ATS guidelines published in 2000, and reviews current knowledge in the epidemiology, etiology, diagnosis and management of IPF, as well as available treatment options, including pharmacologic and non-pharmacologic therapies and palliative care. The statement appears in the March 15, 2011 issue of American Journal of Respiratory and Critical Care Medicine. IPF is a chronic, progressive, fatal form of fibrotic lung disease, characterized by shortness of breath during exertion, which occurs primarily in relatively older adults. The etiology of IPF is unclear. The disease occurs when injury to the lungs is triggered by an unknown cause, resulting in the formation of scar tissue that causes the lungs to become thickened and stiff. IPF may progress slowly over several years and may be punctuated by episodes of acute respiratory decline. Lung transplantation is a feasible treatment option in highly selected patients. A subgroup of patients with IPF has a genetic predisposition to the disease. "In the decade since the publication of the previous statement on IPF, studies have used the criteria for the diagnosis of IPF and recommendations published in the previous consensus-based statement to further our understanding of the clinical manifestations and course of IPF, and there has been an increasing body of evidence pertinent to its clinical management," said Dr. Ganesh Raghu, director of the Interstitial Lung Disease/Sarcoid/Pulmonary Fibrosis Program at the University of Washington Medical Center in Seattle and chair of the collaborative committee that drafted the statement.

Bacteria More Likely to Adopt “Loner” Genes

A new study of more than three dozen bacteria species — including the microbes responsible for pneumonia, meningitis, stomach ulcers and plague — settles a longstanding debate about why bacteria are more likely to steal some genes than others. While most organisms get their genes from their parents just as people do, bacteria and other single-celled creatures also regularly pick up genes from more distant relatives. This ability to 'steal' snippets of DNA from other species — known as lateral gene transfer — is responsible for the rapid spread of drug resistance among disease-causing bacteria. "By understanding why some genes are more likely to spread from one species to the next, we can better understand how new virulent bacterial strains emerge," said co-author Dr. Tal Pupko, a visiting scientist at the National Evolutionary Synthesis Center in Durham, North Carolina. Scientists have proposed several theories to explain why some bacterial genes are more likely to jump into other genomes. One theory, Dr. Pupko explained, is that it depends on what the gene does in the cell. Genes involved in core functions, like converting RNA into protein, are much less likely to make the leap. "If a species already has the basic molecular machinery for transcription and translation, there's no advantage to taking in another set of genes that do the same thing," Pupko said. Other studies suggest it's not what the gene does that matters, but how many proteins it interacts with – a network researchers have dubbed the 'interactome.' Genes involved in transcription and translation, for example, must work in concert with many partners to do their job.

Syndicate content