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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 ( 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.

Half-Way Milestone Reached in Development of Kinase Chemogenomic Set

The Structural Genomics Consortium at the University of North Carolina at Chapel Hill (SGC-UNC), in partnership with the DiscoverX Corporation, has reached the milestone halfway point in its development of the Kinase Chemogenomic Set, a potent group of inhibitors which allow deeper exploration of the human kinome, a family of enzymes critical to understanding human disease and developing new therapies. By building this selective set of compounds and making it freely available, UNC-Chapel Hill and its partners are offering the scientific community a better understanding of the roles the kinome plays in human disease and the ability to collaborate on the discovery and advancement of new therapies. The kinome, made up of enzymes called kinases, provides a tremendous opportunity for drug discovery. While more than 30 kinase inhibitors have been approved for the treatment of disease, the kinome has been largely unexplored until SGC-UNC, DiscoverX, and other SGC partner companies embarked on this project. "Through our collaboration with DiscoverX, we screened a large set of compounds that we call Published Kinase Inhibitor Set 2, and these results allowed us to reach the halfway point in constructing the KCGS" said Dr. David Drewry, a Research Associate Professor at the UNC Eshelman School of Pharmacy and SGC-UNC principal investigator who is leading the project to develop the Kinase Chemogenomic Set. "To mark this milestone and in keeping with our mission of open science, we are releasing these results into the public domain. We sincerely thank all of our co-author partners whose vision, generosity and hard work makes the construction of this set possible." A publication describing the team's strategy and progress toward achieving a comprehensive KCGS was posted online in PLOS ONE on August 2, 2017.

New Research on Fragile X Syndrome Reinforces Importance of Early Detection

Fragile X syndrome--the most common heritable cause of autism spectrum disorder--is something of a phantom. It interferes with the production of a protein critical to synapse formation during a brief period in early development when the brain is optimizing its ability to process sensory input. Then it dials way down...leaving behind permanent changes in neural circuit structure that can cause low IQ, learning disabilities, and hypersensitivity, along with other symptoms characteristic of ASD. This picture of the basic nature of Fragile X has been reinforced by a series of studies reported in a paper titled "Fragile X Mental Retardation Protein Requirements in Activity Dependent Critical Period Neural Circuit Refinement" published in the August 7,2017 issue of Current Biology. The article is titled “Fragile X Mental Retardation Protein Requirements in Activity-Dependent Critical Period Neural Circuit Refinement.” The research was conducted by a team of researchers in the Broadie Laboratory at Vanderbilt University--Kendal Broadie, Stevenson Professor of Neurobiology, postdoctoral fellow Dr. Caleb Doll, and graduate student Dominic Vita--who employed a battery of state-of-the-art techniques to document the effects that the lack of a critical protein caused by the syndrome, called the Fragile X Mental Retardation Protein (FMRP), has on the development of the brain and nervous system of the Drosophila disease model."Our research confirms that the Fragile X protein is essential for refining the brain's ability to process sensory information. The brains of individuals with the syndrome look perfectly normal. They can walk, talk, and chew gum, just not at peak performance," Dr. Broadie said.

PCSK9 Is a Co-Activator of Platelet Function Beyond Its Role In Cholesterol Homeostasis

PCSK9 is a co-activator of platelet function beyond its role in cholesterol homeostasis, according to research presented at European Society of Cardiology (ESC) Congress on August 27, 2017, in Barcelona (August 26-30). The findings suggest that PCSK9 inhibitors, a new class of cholesterol-lowering treatments, may also reduce thrombosis by interfering with platelet activation. Proprotein convertase subtilisin/kexin 9 (PCSK9) is a main player in cholesterol homeostasis by inducing degradation of the low-density lipoprotein (LDL) cholesterol receptor. Emerging evidence indicates that plasma levels of PCSK9 predict recurrent cardiovascular events, for example myocardial infarction and angina, in patients with coronary artery disease, even in those with well controlled LDL cholesterol levels. "We hypothesized that the contribution of PCSK9 to cardiovascular events might be mediated by as yet unknown cholesterol-independent pathways," said last author Dr. Marina Camera, Associate Professor of Pharmacology, University of Milan, Italy. "It has been reported that increased plasma levels of PCSK9 are associated with platelet reactivity. However, no study has so far evaluated whether or not PCSK9 directly affects the function of platelets." Platelets play a key role in the acute, thrombotic complications of atherosclerosis by causing life-threatening ischemic events at a late stage of the disease. Increased platelet activation (called platelet hyperreactivity) has been reported in patients with coronary artery disease and type 2 diabetes mellitus. This study evaluated whether PCSK9 modulates platelet activation. It also assessed whether PCSK9 is expressed in platelets from healthy subjects, stable angina patients, and patients with type 2 diabetes mellitus.

CareFirst BlueCross BlueShield and Exosome Diagnostics Announce Evidence Development Collaboration for Molecular Diagnostic Tests

On August 24, 2017, CareFirst BlueCross BlueShield (CareFirst) and Exosome Diagnostics, Inc. (ExoDx) announced that they have signed an agreement to collaborate on evidence development studies for ExoDx® diagnostic tests. The collaboration is designed to evaluate new products using clinical outcome and cost analyses with the goal of accelerating health plan coverage for products demonstrating measurable benefits for patient care. The agreement is the first in a series of such agreements through CareFirst’s new HealthWorx program, which enables CareFirst to work with small, early-stage companies to bring new technologies and care advances to CareFirst’s members and providers with the goal of improving health care quality and reducing costs. Under the terms of the agreement, CareFirst will become ExoDx’s preferred partner for evidence development studies. CareFirst and ExoDx will mutually agree on the diagnostic tests to be studied, the extent and qualifications of providers participating in these studies, and the study endpoints. The initial collaboration between ExoDx and CareFirst will center on the company’s EPI test (ExoDx® Prostate IntelliScore). The EPI test is a “rule out” test designed to more accurately predict whether a patient presenting for an initial biopsy does not have high-grade prostate cancer and, thus, could potentially avoid the discomfort, complications and cost of an initial biopsy and, instead, continue to be monitored. “One of the challenges presented by prostate-specific antigen (PSA) cancer screenings is the relatively high number of false positives detected from PSA results which often fall into a ‘gray’ zone and require further testing through biopsies,” said Dr. Rahul Rajkumar, CareFirst’s Chief Medical Officer.

Tyrosine Kinase Inhibitor Slows Cyst Growth in Autosomal Dominant Polycystic Kidney Disease (ADPKD) in New Study

A cancer drug called bosutinib may inhibit the growth of cysts in patients with autosomal dominant polycystic kidney disease (ADPKD), according to a study published online on August 24, 2017 in the Journal of the American Society of Nephrology (JASN). The JASN article is titled “Bosutinib Versus Placebo for Autosomal Dominant Polycystic Kidney Disease." The findings point to a potential new treatment strategy for affected patients, but the long-term benefits remain to be determined. ADPKD is an inherited disorder that affects up to 1 in 1000 people and is characterized by cysts in the kidney and other organs. As patients' kidney volume increases due to cyst growth, they gradually lose their kidney function and often develop kidney failure. Current treatments are primarily supportive, such as focusing on hypertension and other secondary complications. The inherited mutations that cause ADPKD affect a protein involved in various signaling pathways that often involve enzymes called tyrosine kinases. Therefore, a team led by Vladimir Tesar, MD, PhD (Charles University and General University Hospital, in the Czech Republic) tested the potential of an investigational drug called bosutinib that inhibits a particular tyrosine kinase called Src/Bcr-Abl. (Bosutinib is approved for the treatment of certain cases of chronic myeloid leukemia). The phase 2 study included patients with ADPKD who were randomized 1:1:1 to bosutinib 200 mg/day, bosutinib 400 mg/day, or placebo. Of 172 patients enrolled, 169 received at least one treatment. The higher dose of bosutinib was not well tolerated. The annual rate of kidney enlargement was reduced by 66% for patients receiving bosutinib 200 mg/day vs. those receiving placebo (1.63% vs. 4.74%, respectively) and by 82% for all patients receiving bosutinib vs.

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