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Archive - Aug 28, 2017

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Novartis Anti-Inflammatory Drug (IL-1ß Inhibitor) Reduces Risk of Cardiovascular Disease and Perhaps Even of Lung Cancer in Patients with Previous Heart Attack and Atherosclerosis

On August 27, 2017, Novartis revealed primary data from CANTOS, a Phase III study evaluating quarterly injections of ACZ885 (canakinumab) in people with a prior heart attack and inflammatory atherosclerosis as measured by high-sensitivity C-reactive protein (hsCRP) levels of >=2mg/L, a known marker of inflammation. Trial participants received either placebo or one of three doses of ACZ885 in combination with current standard of care therapies, with 91% of them taking lipid-lowering statins. The study showed that ACZ885 led to a statistically significant 15% reduction in the risk of major adverse cardiovascular events (MACE), a composite of non-fatal heart attack, non-fatal stroke, and cardiovascular death, compared to placebo (p-value 0.021). This benefit was sustained throughout the duration of the study (median follow up 3.7 years) and was largely consistent across key pre-specified baseline sub groups. The study met the primary endpoint in cardiovascular risk reduction with the 150 mg dose of ACZ885; the 300 mg dose showed similar benefits and the 50 mg dose was less efficacious. The study findings in cardiovascular risk reduction were presented on August 27, 2017 at the European Society of Cardiology (ESC) Congress and published simultaneously in The New England Journal of Medicine. The NEJM article is titled “Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease.” The details of the additional CANTOS lung cancer findings were also presented at ESC and simultaneously published in The Lancet.

Invitation to ASEMV 2017 Annual Meeting (Exosomes & Microvesicles) in Asilomar, California (October 8-12)

The American Society for Exosomes and Microvesicles (ASEMV) is inviting interested scientists to the ASEMV 2017 meeting, to be held October 8-12, 2017 at the Asilomar Conference Center in California. This center is located on the Monterrey peninsula, just south of San Francisco (www.visitasilomar.com). The meeting will cover the full breadth of the exosome field, from basic cell biology to clinical applications, and follow the ASEMV tradition of inclusion and diversity as participants learn about the latest advances in the field. ASEMV 2017 is a forum for learning the latest discoveries in the field of exosomes, microvesicles, and extracellular RNAs. Over the course of four days at the Asilomar Conference Center, ASEMV 2017 will offer presentations from leading scientists and young researchers. Topics will span the breadth of the extracellular vesicle/RNA field, including the basic sciences, disease research, translation efforts, and clinical applications. Talks will be presented in multiple sessions, beginning at 7 pm on Sunday, October 8, 2017, and concluding at 4 pm on Thursday, October 12, 2017. Poster sessions will run throughout the meeting, with ample time to get to know your colleagues in the field and explore the many opportunities in this rapidly expanding field. Please see the links below.

Symptom Severity in Neuropsychiatric Disorder (Functional Neurological Disorder) Associated with Structural Changes Within Brain Network

An imaging study by Massachusetts General Hospital (MGH) investigators has identified differences in key brain structures of individuals whose physical or mental health has been most seriously impaired by a common, but poorly understood, condition called functional neurological disorder (FND). In their report published online on August 26, 2017 in the Journal of Neurology, Neurosurgery and Psychiatry (JNNP), the research team describes reductions in the size of a portion of the insula in FND patients with the most severe physical symptoms and relative volume increases in the amygdala among those most affected by mental health symptoms. The article is titled “Corticolimbic Structural Alterations Linked to Health Status and Trait Anxiety in Functional Neurological Disorder.” "The brain regions implicated in this structural neuroimaging study are areas involved in the integration of emotion processing, sensory-motor, and cognitive functions, which may help us understand why patients with functional neurological disorder exhibit such a mix of symptoms," says David Perez, MD, MMSc, of the MGH Departments of Neurology and Psychiatry, the lead and corresponding author of the report. "While this is a treatable condition, many patients remain symptomatic for years, and the prognosis varies from patient to patient. Advancing our understanding of the pathophysiology of FND is the first step in beginning to develop better treatments." One of the most common conditions bringing patients to neurologists, FND involves a constellation of neurologic symptoms - including weakness, tremors, walking difficulties, convulsions, pain, and fatigue - not explained by traditional neurologic diagnoses. This condition has also been called conversion disorder, reflecting one theory that patients were converting emotional distress into physical symptoms, but Dr.

Study of Worm Infection Reveals Cross-Talk in Lymph Nodes

Lymph nodes are small, kidney-shaped organs found throughout the body. Full of immune cells, the lymph nodes’ function is to clear out foreign objects and support the immune system. Lymph nodes communicate with the tissues and with each other through the lymphatic vessels, which carry fluids and objects from the tissues and back out to the bloodstream. Normally, lymphatic vessels grow during the embryo stage, but also in adults during wound healing, cancer, and inflammation. But the exact mechanism of this "lymphangiogenesis" is yet unknown. Ecole Polytechnique Fédérale de Lausanne (EPFL) scientists have now identified the molecules that signal the growth of lymphatic vessels during worm infections. The work was published on August 28, 2017 in Nature Communications. The open-access article is titled “Interactions Between Fibroblastic Reticular Cells and B Cells Promote Mesenteric Lymph Node Lymphangiogenesis.” The lymphatic vessels drain pathogens from tissues to the collecting lymph nodes, where immune responses begin. These vessels also allow lymphocytes and dendritic cells --which expose pathogen material to trigger the immune system -- to flow in and out of the lymph nodes. Because of this, lymphangiogenesis is important for immune responses against infections. But recent studies have shown that lymphangiogenesis can also regulate immune responses during inflammation. This connection between inflammation and lymphangiogenesis is key in our understanding of the adaptive immune response, which is the slower but more specialized wave against infections and involves T and B cells. The lab of Dr. Nicola Harris at EPFL looked at the mesenteric lymph node, which collects fluids and material from the intestine of mice. The research, led by Dr.

Microbes Compete for Nutrients, Affect Metabolism & Development in Mice

"Gut bacteria get to use a lot of our food before we do," says Dr. Federico Rey, a Professor of Bacteriology at the University of Wisconsin-Madison. Then we get their leftovers -- or their waste. The problem, says Dr. Rey, is that if our microbiome overindulges, we might not have access to the nutrients we need. That's the suggestion from new research conducted by Dr. Rey's group that shows mice that harbor high levels of microbes that eat choline are deprived of this essential nutrient. Compared to mice without choline-hungry bacteria, the choline-starved mice had an increased susceptibility to metabolic diseases and gave birth to pups with biochemical alterations in the brain and that exhibited more anxious behaviors. The study was published online on July 31, 2017 in Cell Host & Microbe. UW-Madison Professor of Bacteriology Daniel Amador-Noguez and researchers from Harvard University also contributed to the work. The article is titled “Metabolic , Epigenetic, and Transgenerational Effects of Gut Bacterial Choline Consumption.” Epigenetic regulation -- the decorating of genes with chemical groups that control how much they are expressed -- appears to underlie the effects of gut bacteria that consume too much choline. Choline contributes to the pool of resources that cells use to make these modifications to DNA, and with less choline available, the cell's ability to modify and regulate genes can be impaired. Tissues from the liver to the brain had altered epigenetic patterns in mice with high levels of choline-eating microbes. "Epigenetic modifications change how genes are expressed," explains Kym Romano, a graduate student in Dr. Rey's group and one of the lead authors of the new research.