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Archive - Jun 2017

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June 15th

Broccoli Extract Improves Glucose Control in Type 2 Diabetes

Researchers have identified an antioxidant – richly occurring in broccoli – as a new antidiabetic substance. A patient study shows significantly lower blood sugar levels in participants who ate broccoli extract with high levels of sulforaphane. “There are strong indications that this can become a valuable supplement to existing medication,” says Dr. Anders Rosengren, Docent in Metabolic Physiology at the University of Gothenburg in Sweden and affiliated with the Lund University Diabetes Centre. Publication of the finding in the June 14, 2017 issue of Science Translational Medicine builds on several years’ research at Sahlgrenska Academy, University of Gothenburg, and the Faculty of Medicine at Lund University. The open-access article is titled “Sulforaphane Reduces Hepatic Glucose Production and Improves Glucose Control in Patients with Type 2 Diabetes.” The objective of the study was to find new medications against type 2 diabetes by addressing an important disease mechanism: the liver’s elevated glucose production. The classic drug metformin works by doing just that, but often causes gastric side-effects and can also not be taken when kidney function is severely reduced, which affects many with diabetes. The researchers began by mapping the genetic changes in the liver in diabetes. 50 genes proved to play key roles. These were then matched against different substances in the search for compounds that could affect these particular key genes, and thereby attack the disease on a broad front. Of 2,800 substances investigated through computer-based mathematical analyses, sulforaphane proved to have the best characteristics for the task. An antioxidant that was previously studied for the treatment of cancer and inflammatory disease, but not for diabetes was thereby identified.

June 14th

New Mutation Identified for Rare Genetic Kidney Disease (MCKD1); Mutant Protein Can Be Detected in Urinary Exosomes, Offering Possible Biomarker for Early Detection of Disease

Medullary cystic kidney disease type 1 (MCKD1) is an autosomal dominant tubulointerstitial kidney disease (ADTKD). Recently, mucin 1 (MUC1) was identified as a causal gene MCKD1. However, the identified MUC1 mutation was found to be a single cytosine insertion in a single copy of the GC-rich variable number of tandem repeats (VNTRs), which are very difficult to analyze by next-generation sequencing. Until now, other mutations had not been detected in ADTKD-MUC1, and the mutant MUC1 protein has not been analyzed because of the difficulty of genetically modifying the VNTR sequence. Now, a second mutation in the causal gene has been identified and this advance may enable earlier detection of the disease, perhaps via protein analysis of urinary exosomes. Despite the general rarity of MCKD1, because it is an autosomal dominant disease, once a causative mutation is in a family, many family members can be affected. Current diagnostic methods discover the disease only late in its development. Recently, Osaka University (Japan) researchers studied one family in which 9 of 26 members were positive for MCKD1 and identified the new mutation in the disease-associated mucin 1 (MUC1) gene that may act as an early marker of the disease. “Besides renal failure and genetic testing, there is little we have to identify the disease,” says Associate Professor Jun-Ya Kaimori, a nephrologist at Osaka University Hospital. “There are very few early signs that show illness.” At the point of renal failure, patients are usually left with only extreme and invasive treatment options, such as dialysis or transplantation. “MCKD1 is caused by a single mutation in MUC1 gene discovered in 2013,” he continued. This mutation is located in a region of the gene that includes GC-rich variable number of tandem repeats (VNTRs). This, explains Dr.

June 13th

DNA Methylation (Epigenetic) Changes Present at Birth Could Explain Later Behavior Problems

Epigenetic changes present at birth - in genes related to addiction and aggression - could be linked to conduct problems in children, according to a new study by researchers at King's College London and the University of Bristol. Conduct problems (CP) such as fighting, lying, and stealing are the most common reason for child treatment referral in the UK, costing an enormous amount of money each year. Children who develop conduct problems before the age of 10 (known as early-onset CP) are at a much higher risk for severe and chronic antisocial behavior across the lifespan, resulting in further social costs related to crime, welfare dependence, and health-care needs. Genetic factors are known to strongly influence conduct problems, explaining between 50-80 per cent of the differences between children who develop problems and those who do not. However, little is known about how genetic factors interact with environmental influences - especially during fetal development - to increase the risk for later conduct problems. Understanding changes in DNA methylation, an epigenetic process that regulates how genes are “switched on and off,” could aid the development of more effective approaches to preventing later conduct problems. The study, published online on June 12, 2017, in Development & Psychopathology, used data from Bristol's Avon Longitudinal Study of Parents and Children (ALSPAC) to examine associations between DNA methylation at birth and conduct problems from the ages of 4 to 13. The researchers also measured the influence of environmental factors previously linked to early onset of conduct problems, including maternal diet, smoking, alcohol use, and exposure to stressful life events.

Scientists Make First Crystal Model of Molecular Interactions in Under-Diagnosed Autoimmune Disease (Myasthenia Gravis); 3D Model Shows Interactions Between Auto-Antibodies and Auto-Antigen

As a molecular biologist, Kaori Noridomi gets an up-close view of the targets of her investigations. But when she began studying the molecular structures of a rarely diagnosed autoimmune disorder, myasthenia gravis, she decided to step out of the lab for a better view. Dr. Noridomi said she thought she needed to know more than what she saw under a microscope and decided she should meet patients who have myasthenia gravis. She went so far as to attend a fundraising walk that supported research of the disease. "Patients are just waiting for breakthroughs in research and better treatment," said Noridomi, a researcher in Professor Lin Chen's Molecular and Computational Biology lab at the University of Southern California (USC) Dornsife College of Letters, Arts and Sciences. "They may also, because the disease attacks their immune system, end up with other diseases. I met one patient who had myasthenia gravis and had also dealt with four different types of cancer." Motivated by the patients' stories, Noridomi and a team of scientists, including Professor Chen (photo), developed a 3-D, crystal structure of the disease's molecular interactions to fully view its molecular interactions with a neural receptor that is the regular target of the disease. It is the first, high-resolution visual display of the molecular interactions. The development of the crystal structure gives scientists a clear view of how exactly the disease behaves and interferes with brain-to-muscle signals. The ability to see these interactions will likely accelerate research of the disease and could possibly lead to new disease-targeting therapies, said Dr. Chen, the study's corresponding author and a USC Dornsife College Professor of Biological Sciences and Chemistry. "Because of this finding, we may also find a better quantitative way to identify patients," Dr. Chen said.

June 12th

Possible “Game-Changer in Treatment of Type 2 Diabetes” Canagliflozin (Invokana) Drug Reduces Risks of Cardiovascular Disease, Heart Failure Hospitalization, and Kidney Disease Progression, According to Study Published in NEJM

A drug that lowers blood sugar levels for people with type 2 diabetes has also been revealed to significantly reduce the risk of both cardiovascular and kidney disease. The study by The George Institute for Global Health has major implications for the treatment of type 2 diabetes, which affects approximately 450 million people worldwide. The findings published online on June 12, 2017 in the New England Journal of Medicine found that the drug canagliflozin (Invokana) reduced the overall risk of cardiovascular disease by 14 per cent and reduced the risk of heart failure hospitalization by 33 per cent. It was also shown to have a significant impact on the progression of renal disease. Professor Bruce Neal, of The George Institute for Global Health, said the findings, which were presented at the American Diabetes Association Conference in San Diego (June 9-13) were exciting and offered real hope to people suffering from type 2 diabetes. "Coronary heart disease is the biggest killer by far for people with type 2 diabetes. Our findings suggest that not only does canagliflozin significantly reduce the risk of heart disease, it also has many other benefits too. We found it also reduced blood pressure and led to weight loss. Type 2 diabetes is growing rapidly all over the world and we need drugs that not only deal with glucose levels, but that also protect the many millions of people from the very real risks of stroke and heart attack." The study is particularly important to Australiaa because approximately 65% of all cardiovascular deaths occur in people with diabetes or pre-diabetes, and diabetes is also the leading cause of end-stage kidney disease. It also reinforces the findings from a previous study which also showed a reduced risk of cardiovascular disease associated with blood-sugar-level-lowering drugs.

Small Group of Hypothalamus Neurons (POMC) Modulates Amount of Insulin Pancreas Produces

The brain is key in the regulation of appetite, body weight, and metabolism. Specifically, there is a small group of hypothalamus neurons, called POMC (pro-opiomelanocortin) neurons, that detect and integrate signals that inform on the energy state of the organism and activate the appropriate physiological responses. These neurons are sensitive to fluctuations in nutrients such as glucose, fatty acids, and amino acids. Now, a research project co-chaired by Marc Claret, at the August Pi i Sunyer Biomedical Research Institute (IDIBAPS), and Antonio Zorzano, at the Institute for Research in Biomedicine (IRB Barcelona), both members of the CIBERDEM network, reveals the connection between POMC neurons at the hypothalamus and the release of insulin by the pancreas and describes new molecular mechanisms involved in this connection. The study was published in the June 6, 2017 issue of Cell Metabolism and the first authors are Sara Ramírez and Alicia G. Gómez-Valadés, both at IDIBAPS. The article is titled “Mitochondrial Dynamics Mediated by Mitofusin 1 Is Required for POMC Neuron Glucose-Sensing and Insulin Release Control.” POMC neurons detect changes in nutrient availability, but the molecular mechanisms involved are not known in detail. Also changes in the shape of mitochondria, a phenomenon known as mitochondrial dynamics, is a mechanism of energy adaptation in changing metabolic conditions, to adjust the needs of cells. To determine whether defects in the mitochondrial dynamics of this small nucleus of POMC neurons could cause alterations in metabolism, researchers removed a mitochondrial dynamics protein, mitofusin 1, in these cells in mice. First, the scientists observed that these mice have altered detection of glucose levels and adaptation between the fasting state and after being fed.

Liquid Biopsy Propelling Cancer Diagnostics Research Is Focus of Mid-Morning Session on Day 2 of Personalized Medicine World Conference (PMWC) 2017 at Duke; GRAIL Founder Richard Klausner Speaks

Speakers in the mid-morning session of Day 2 of the PMWC 2017 at Duke focused on how “Liquid Biopsy Is Propelling Cancer Diagnostics Research.” The speakers included Richard Klausner, MD, former Director of the National Cancer Institute, past Chief Medical Officer at Illumina, and a founder of GRAIL, Inc. (https://grail.com/), a life sciences company whose mission is to detect cancer early, when it can be cured, using wide and deep DNA sequencing analysis of circulating cell-free DNA (cfDNA); John Beeler, PhD, VP of Corporate & Business Development, Inivata (https://www.inivata.com/), a company dedicated to transforming clinical cancer care with liquid biopsy; and Edward Kim, MD, Chair of Solid Tumor Oncology and Investigational Therapeutics and the Donald S. Kim Distinguished Chair for Cancer Research at the Levine Cancer Institute, Carolinas HealthCare System in Charlotte, North Carolina. Dr. Kim was previously at UT MD Anderson Cancer Center in Houston, Texas where he was a tenured Associate Professor of Medicine, Chief of the Section of Head and Neck Medical Oncology, and Director of Clinical Research Operations in the Department of Thoracic/Head and Neck Medical Oncology. Dr. Klausner began the session by briefly telling the story of how GRAIL, a company that recently raised $900 million in funding, came to be. The story began not too long ago at Illumina, the biotech company where Dr. Klausner was CMO. Illumina had developed a highly specific and precise liquid biopsy test (Noninvasive Prenatal Testing) that could detect aberrant chromosome numbers (monosomies and trisomies) in fetal DNA in blood taken from expectant mothers as early as 10 weeks into the pregnancy. Dr. Klausner said that this test became the most rapidly adopted test in history.

June 11th

New Trends and Emerging Technologies Are Focus of Morning Session on Day 2 of Personalized Medicine World Conference (PMWC) 2017 at Duke

After the morning’s opening panel discussion on “The Value of Data Sharing,” Day 2 of the Personalized Medicine World Conference (PMWC) 2017 at Duke continued with a high-energy, high-impact presentation by Mark Levin (photo), Co-Founder of Third Rock Ventures in the session on “New Trends and Emerging Technologies.” Other speakers in this session included John Mikszta PhD, Director of the Genomic Sciences Focus Area at BD Technologies; Lawrence David, PhD, Assistant Professor, Department of Molecular Genetics and Microbiology and Center for Genomics & Computational Biology at Duke University; and Panna Sharma, President and CEO, Cancer Genetics, Inc. Dr. Mikszta spoke on ”Single-Cell Genomics: Emerging Applications,” Dr. David spoke on “The Role of the Human Microbiome,”and Dr. Sharma spoke on “How AI Is Accelerating and Enabling Precision Oncology.” Mark Levin has been a life science leader for 40 years, most of them spent conceiving and launching biotechnology companies. Early on, Levin recognized that personalized medicine had the potential to benefit the patient and revolutionize both pharma and biotech. He strongly espoused that the only way the field would reach this potential was if all stakeholders banded together to overcome the many challenges it faced. To enable this, he helped conceive the Personalized Medicine Coalition. In 2007, Levin co-founded Third Rock Ventures, a different kind of venture capital firm that actively searched for disruptive medical technology and innovative science, to build into companies from the ground up. Many of these were based on personalized medicine, such as cancer epigenetics, gene therapy and molecular diagnostics. Then, he and his partners carefully selected the founding teams and instilled them with a sustainable culture.

June 10th

Mass General Study Finds Potential Mechanism for BCG Vaccine Reversal of Type 1 Diabetes; Data Presented at ADA Meeting Indicates Increase in Expression of Genes Restoring Function of Beneficial Treg Cells

Interim results from an FDA-approved clinical trial testing the generic vaccine bacillus Calmette-Guérin (BCG) to reverse advanced type 1 diabetes are being presented at the 77th Scientific Sessions of the American Diabetes Association (June 9-13, San Diego). The data demonstrate a potential new mechanism by which the BCG vaccine may restore the proper immune response to the insulin-secreting islet cells of the pancreas. Presented by Denise Faustman (photo), MD, PhD, Director of the Massachusetts General Hospital Immunobiology Laboratory and principal investigator of the trial, the findings suggest that BCG may induce a permanent increase in the expression of genes that restore the beneficial regulatory T cells (Tregs) that prevent the immune system from attacking the body's own tissue. The results are being presented on Saturday, June 10. "Many groups are looking at the ability of BCG vaccination to reverse autoimmunity," says Dr. Faustman, who is an Associate Professor of Medicine at Harvard Medical School. "We and other global efforts have known for some time that restoring beneficial Treg cells might halt the abnormal self-reactivity in type 1 diabetes and other autoimmune diseases, but therapies to restore this immune balance have not achieved long-lasting results. The discovery that BCG restores Tregs through epigenetics - a process that modulates whether or not genes are expressed - is exciting. This now provides a better idea of how BCG vaccination appears to work by powerfully modulating Treg induction and resetting the immune system to halt the underlying cause of the disease." Type 1 diabetes is an autoimmune disease characterized by the destruction of islets by autoreactive T cells, which mistakenly attack islets as if they were an infection.

Five Years Before Brain Cancer Diagnosis, Cytokine Changes Are Detectable in Blood

Changes in immune activity appear to signal a growing brain tumor five years before symptoms arise, new research has found. Interactions among proteins that relay information from one immune cell to another are weakened in the blood of brain cancer patients within five years before the cancer is diagnosed, said lead researcher Dr. Judith Schwartzbaum of The Ohio State University. That information could one day lead to earlier diagnosis of brain cancer, said Dr. Schwartzbaum, an Associate Professor of Epidemiology and member of Ohio State's Comprehensive Cancer Center. The study, published online on June 8, 2017 in the journal PLOS ONE, focused on gliomas, which make up about 80 percent of brain cancer diagnoses. Average survival time for the most common type of glioma is 14 months. The open-access PLOS ONE article is titled “A Nested Case-Control Study of 277 Prediagnostic Serum Cytokines and Glioma.” Symptoms vary and include headaches, memory loss, personality changes, blurred vision and difficulty speaking. On average, the cancer is diagnosed three months after the onset of symptoms and when tumors are typically advanced. "It's important to identify the early stages of tumor development if we hope to intervene more effectively," Dr. Schwartzbaum said. "If you understand those early steps, maybe you can design treatments to block further tumor growth." While widespread blood testing of people without symptoms of this rare tumor would be impractical, this research could pave the way for techniques to identify brain cancer earlier and allow for more-effective treatment, Dr. Schwartzbaum said. Dr. Schwartzbaum evaluated blood samples from 974 people, half of whom went on to receive a brain-cancer diagnosis in the years after their blood was drawn. The samples came from Norway's Janus Serum Bank.