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Archive - 2019

March 18th

Blood Test Using Vibrational Spectroscopy Accurately Spots Molecular Signature of Fibromyalgia; “Could Lead to Better, More Directed Treatment for Patients," Lead Researcher Says; Unusual Collaboration with Food Science Group Key to Advance

For the first time, researchers have evidence that fibromyalgia can be reliably detected in blood samples -- work they hope will pave the way for a simple, fast diagnosis. In a study published in the February 15, 2019 issue of the Journal of Biological Chemistry, researchers from The Ohio State University report success in identifying biomarkers of fibromyalgia and differentiating it from a handful of other related diseases. Their article is titled “Metabolic Fingerprinting for Diagnosis of Fibromyalgia and Other Rheumatologic Disorders.” The discovery could be an important turning point in care of patients with a disease that is frequently misdiagnosed or undiagnosed, leaving them without proper care and advice on managing their chronic pain and fatigue, said lead researcher Kevin Hackshaw (photo), MD, an Associate Professor in Ohio State's College of Medicine and a rheumatologist at the University's Wexner Medical Center. Identification of biomarkers of the disease - a "metabolic fingerprint" like that discovered in the new study - could also open up the possibility of targeted treatments, he said. To diagnose fibromyalgia, doctors now rely on patient-reported information about a multitude of symptoms and a physical evaluation of a patient's pain, focusing on specific tender points, he said. But there's no blood test - no clear-cut, easy-to-use tool to provide a quick answer. "We found clear, reproducible metabolic patterns in the blood of dozens of patients with fibromyalgia. This brings us much closer to a blood test than we have ever been," Dr. Hackshaw said.

March 14th

Huntington Disease Rate of Progression Determined by Length of Uninterrrupted CAG Repeats in DNA, Not Length of Polyglutamine Segment of Mutant Huntingtin Protein; Results Point to Importance of DNA Maintenance Mechanisms

HIn a preprint posted on January 24, 2019 by Cold Spring Harbor Laboratory’s bioRxiv, the Genetic Modifiers of Huntington’s Disease Consortium (GeM-HD), including such prominent HD experts as James Gusella, PhD, and Marcy MacDonald, PhD, both of the Molecular Neurogenetics Unit, Center for Genomic Medicine, Massachusetts General Hospital; and Jane Paulsen, PhD, Departments of Psychiatry and Neurology, University of Iowa, make the provocative suggestion that some property of the uninterrupted CAG repeat segment in exon 1 of the huntingtin-coding gene (HTT), distinct from the resulting too-lengthy polyglutamine segment of the huntingtin protein, determines the rate at which HD develops. The article is titled “Huntington's Disease Onset Is Determined by Length of Uninterrupted CAG, Not Encoded Polyglutamine, and Is Modified by DNA Maintenance Mechanisms” (( According to the article abstract, “The timing of onset shows no significant association with HTT cis-eQTLs, but is influenced, sometimes in a sex-specific manner, by polymorphic variation at multiple DNA maintenance genes, suggesting that the special onset-determining property of the uninterrupted CAG repeat is a propensity for length instability that leads to its somatic expansion. Additional naturally-occurring genetic modifier loci, defined by GWAS, may influence HD pathogenesis through other mechanisms.

Heart Uses Exosomes to Send SOS Signal to Bone Marrow (BM) Cells After Heart Attack; In BM, Exosomes Release Heart-Specific MicroRNAs That Down-Regulate CXCR4 & Stimulate BM Progenitor Cells to Enter Blood Stream & Travel to Heart to Attempt Repairs

Human cells release exosomes. These tiny, membrane-bound vesicles can carry cargo for cell-to-cell communication, with the ability to ferry diverse loads of proteins, lipids, and/or nucleic acids. Researchers at the University of Alabama at Birmingham (UAB) and in China now report that exosomes are key to the SOS signal that the heart muscle sends out after a heart attack. After the heart attack, the exosomes in the bloodstream carry greatly increased amounts of heart-specific microRNAs — an observation seen in both mice and humans. These exosomes preferentially carry the microRNAs to progenitor cells in the bone marrow. Inside those progenitor cells, the microRNAs turn off a specific gene that allows the progenitor cells to leave the bone marrow and enter the bloodstream. The cells then travel to the heart to attempt repairs. The investigators say discovery of this novel pathway — a signal from the damaged heart to a systemic response by the reparative bone marrow cells — can now be leveraged to improve cell-based cardiovascular repair after heart attacks. The study — led by Gangjian Qin, MD, Professor in the UAB Department of Biomedical Engineering and Director of the Molecular Cardiology Program, and Min Cheng, MD, PhD, Huazhong University of Science and Technology, Wuhan, China — was published online on February 27, 2019 in Nature Communications. The open-access article is titled “Circulating Myocardial MicroRNAs from Infarcted Hearts Are Carried in Exosomes and Mobilize Bone Marrow Progenitor Cells.” For 15 years, it had been known that progenitor cells are released from the bone marrow after a heart attack. These cells move to the damaged heart muscle to attempt repairs. However, many efforts to improve that repair have yielded only modest efficacies, at best.

March 13th

New Genetic Data on 50,000 UK Biobank Participants Made Available to Global Health Research Community—"“We Believe This Is the Largest Open-Access Resource of Exome Sequence Data Linked to Robust Health Records in the World," Regeneron SVP Says

A vast tranche of new UK Biobank genetic data became available to health researchers on March 11, 2019, offering an unprecedented resource to enhance understanding of human biology and aid in therapeutic discovery. The exome sequence data of 50,000 UK Biobank participants was generated at the Regeneron Genetics Center through a collaboration among UK Biobank, Regeneron (US), and GSK (GlaxoSmithKline - UK) and are linked to detailed health records, imaging, and other health-related data. Regeneron is also leading a consortium of biopharma companies (including Abbvie, Alnylam, AstraZeneca, Bristol-Myers Squibb, Biogen, Pfizer, and Takeda) to complete exome sequencing of the remaining 450,000 UK Biobank participants by 2020. In addition, GSK has committed a £40 million (~$53 million) investment to initiatives, such as UK Biobank, that harness advances in genetic research in the development of new medicines. Consistent with the founding principles of UK Biobank, the first tranche of data has now been incorporated back into the UK Biobank resource for the global health research community to use. It follows a brief exclusive research period for Regeneron and GSK. Additional tranches of data will similarly be released over the next two years. All sequencing and analyses activities are undertaken on a de-identified basis, with the utmost consideration and respect for participant privacy and confidentiality principles. This major enhancement to UK Biobank would have been unimaginable when the study began recruiting participants in 2006, and makes it one of the most important studies of population health in the world.

Large New Study (Over 35,000 Individuals with Late-Onset AD, Over 94,000 Total) Identifies Five Additional Genes That Put People at Greater Risk of Alzheimer’s Disease—Dr. Francis Collins Comments in NIH Director’s Blog

Predicting whether someone will get Alzheimer’s disease (AD) late in life, and how to use that information for prevention, has been an intense focus of biomedical research. The goal of this work is to learn, not only about the genes involved in AD, but how they work together, and with other complex biological, environmental, and lifestyle factors to drive this devastating neurological disease. It’s good news to be able to report that an international team of researchers, partly funded by NIH, has made more progress in explaining the genetic component of AD. Their analysis, involving data from more than 35,000 individuals with late-onset AD, has identified variants in five genes that put people at greater risk of AD. It also points to molecular pathways involved in AD as possible avenues for prevention, and offers further confirmation of 20 other genes that had been implicated previously in AD. The results of this largest-ever genomic study of AD suggest key roles for genes involved in the processing of beta-amyloid peptides, which form plaques in the brain recognized as an important early indicator of AD. The results also offer the first evidence for a genetic link to proteins that bind tau, the protein responsible for tell-tale tangles in the AD brain that track closely with a person’s cognitive decline. The Nature Genetics article summarizing this work was published online on February 28, 2019, and is titled “Genetic Meta-Analysis of Diagnosed Alzheimer’s Disease Identifies New Risk Loci and Implicates Aβ, Tau, Immunity, and Lipid Processing.”

March 12th

“Join the the R-EV-olution!” Highlights from 3rd Annual Mid-Atlantic Extracellular Vesicle (EV) Scientific Symposium

(BY RACHEL DERITA, PhD,Thomas Jefferson University, Department of Cancer Biology). The field of extracellular vesicles (EVs) is expanding rapidly and this was never more evident than when a group of prominent leaders in the field, and scientists more recently entering the field, all came to The Wistar Institute in Philadelphia, Pennsylvania for the 3rd Annual Mid-Atlantic Extracellular Vesicle Scientific Symposium on February 26, 2019. The Symposium provided an opportunity for veteran EV researchers from different backgrounds, and scientists who have more recently entered the field, to both present their research and network with each other to exchange insights on this exciting and accelerating field that seems more important in more different areas almost every week. The Symposium began with a talk by Kenneth Witwer, PhD, Associate Professor of Molecular and Comparative Pathobiology at Johns Hopkins University, and a Co-Chair of the Symposium, who is also Executive Chair of the International Society of Extracellular Vesicles (ISEV). Recently, Dr. Witwer and Clotilde Thery, PhD, INSERM Director of Research at the Institut Curie, and over 380 other contributing ISEV members, published the “Minimal Information for Studies of Extracellular Vesicles 2018 (MISEV 2018) in the Journal of Extracellular Vesicles. This is an update to guidelines first published in 2014 in response to a need for increased methodologic understanding and rigor in the EV field. Dr. Witwer highlighted some of the most important updates made to MISEV since 2014. The most prominent of these was in the nomenclature of EVs.

Gene (MT-ATP6) Behind Long-Recognized Mitochondrial Disease Has Highly Varied Effects; CHOP Researchers Find More Than 30 Variations in MT-ATP6 Gene with Broadly Variable Clinical Symptoms and Biochemical Features

For more than two decades, mutations in a gene located in the DNA of mitochondria have been classified as a mitochondrial disease and linked to a particular set of symptoms. However, according to new findings from researchers at Children's Hospital of Philadelphia (CHOP), mutations in this gene, which encodes an essential part of the mitochondrial motor known as ATP synthase that generates cellular energy, are much more variable than previously thought. This prompts the need to develop more precise clinical tests that can better determine the course of treatment for patients affected by mitochondrial disorder. The study was published online on February 14. 2019 in the journal Human Mutation. The article is titled “"MT-ATP6 Mitochondrial Disease Variants: Phenotypic and Biochemical Features Analysis in 218 Published Cases and Cohort of 14 New Cases." Mitochondria are structures found within human and animal cells that are responsible for energy production. Mitochondria contain 37 genes encoded in their own DNA (mtDNA) that are separate from the DNA found inside the nucleus of the cell. Variations in more than 350 different genes located across both nuclear and mitochondrial DNA are responsible for causing mitochondrial diseases, which can typically cause more than 16 different symptoms in each patient and affect multiple organs. Mutations in the mtDNA-encoded ATP synthase membrane subunit 6 gene (MT-ATP6) are found in between 10 and 20 percent of cases of Leigh syndrome, a progressive brain disorder long recognized as a form of mitochondrial disease, and another recognizable condition known as neuropathy, ataxia, and retinitis pigmentosa (NARP) syndrome.

March 11th

tACS (Transcranial Alternating Current Stimulation) of Brain Improves Symptoms of Major Depression, Restores Brain Waves in Clinical Study; New Approach Might Significantly Help Depressed Patients in Inexpensive, Non-Invasive Way, Lead Researcher Says

University of North Carolina (UNC) School of Medicine researchers, led by Flavio Frohlich, Ph.D., are the first to use transcranial alternating current brain stimulation (tACS) to significantly reduce symptoms in people diagnosed with major depression. With a weak alternating electrical current sent through electrodes attached to the scalp, University of North Carolina (UNC) School of Medicine researchers successfully targeted a naturally occurring electrical pattern in a specific part of the brain and markedly improved depression symptoms in about 70 percent of participants in a clinical study. The research, published online on March 5, 2019 in Translational Psychiatry, lays the groundwork for larger research studies to use a specific kind of electrical brain stimulation called transcranial alternating current stimulation (tACS) to treat people diagnosed with major depression. The open-access article is titled “Double-blind, randomized pilot clinical trial targeting alpha oscillations with transcranial alternating current stimulation (tACS) for the treatment of major depressive disorder (MDD).” "We conducted a small study of 32 people because this sort of approach had never been done before," said senior author Flavio Frohlich, PhD, Associate Professor of Psychiatry and Director of the Carolina Center for Neurostimulation. "Now that we've documented how this kind of tACS can reduce depression symptoms, we can fine-tune our approach to help many people in a relatively inexpensive, noninvasive way." Dr. Frohlich, who joined the UNC School of Medicine in 2011, is a leading pioneer in this field who also published the first clinical trials of tACS in schizophrenia and chronic pain. Dr.

Roche's VENTANA PD-L1 (SP142) Assay Approved As First Companion Diagnostic to Identify Triple-Negative Breast Cancer Patients Eligible for Treatment with Tecentriq in Combination with Abraxane

On March 11, 2019, Roche (SIX: RO, ROG; OTCQX: RHHBY) announced the the US Food and Drug Administration had approved the VENTANA PD-L1 (SP142) Assay as the first companion diagnostic to aid in identifying triple-negative breast cancer (TNBC) patients eligible for treatment with the Roche cancer immunotherapy Tecentriq® (atezolizumab) plus chemotherapy (Abraxane® [paclitaxel protein-bound particles for injectable suspension (albumin-bound); nab-paclitaxel]). Assessment of PD-L1 biomarker status on tumor-infiltrating immune cells with the assay is essential for identifying those patients most likely to benefit from the treatment. A diagnosis of triple-negative breast cancer means that the three most common proteins associated with breast cancer growth (estrogen receptor, progesterone receptor, and HER2/neu) are not expressed on the tumor. "Triple-negative breast cancer is an aggressive disease that, until now, has had limited treatment options," said Michael Heuer, CEO of Roche Diagnostics. "This assay plays a pivotal role in helping physicians identify patients who can benefit from Tecentriq therapy, providing better patient care. At Roche, we build on our capacity to research both targeted medicines and companion diagnostics under one roof, so we can provide the right treatment to the right patient at the right time." Each year about 300,000 women are diagnosed globally with triple-negative breast cancer, an aggressive disease with limited treatment options that represents 15 percent of all breast cancer cases. The VENTANA PD-L1 (SP142) Assay was developed to enhance visual contrast of tumor-infiltrating immune cell staining. In triple-negative breast cancer, PD-L1 is primarily expressed on tumor-infiltrating immune cells rather than on tumor cells themselves.

FDA Grants Roche’s Tecentriq, in Combination with Abraxane, Accelerated Approval for People With PD-L1-Positive, Metastatic Triple-Negative Breast Cancer; First Cancer Immunotherapy Regimen Approved for Breast Cancer

On March 11, Roche (SIX: RO, ROG; OTCQX: RHHBY) announced that the US Food and Drug Administration (FDA) has granted accelerated approval to Tecentriq® (atezolizumab) (an anti-PD-L1 monoclonal antibody), plus chemotherapy (Abraxane® [paclitaxel protein-bound particles for injectable suspension (albumin-bound); nab-paclitaxel]), for the treatment of adults with unresectable, locally advanced or metastatic triple-negative breast cancer (TNBC) in people whose tumors express PD-L1, as determined by an FDA-approved test. “The FDA approval of this Tecentriq combination is an important treatment advance for people with PD-L1-positive, metastatic triple-negative breast cancer, a disease with high unmet medical need,” said Sandra Horning, MD, Roche’s Chief Medical Officer and Head of Global Product Development. “This Tecentriq combination is the first cancer immunotherapy regimen to be approved in breast cancer, representing a meaningful step forward in the understanding of this disease.” This indication is approved under accelerated approval based on progression-free survival (PFS). Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s). The FDA’s Accelerated Approval Program allows conditional approval of a medicine that fills an unmet medical need for a serious or life-threatening disease or condition. This accelerated approval is based on data from the Phase III IMpassion130 study, which demonstrated that Tecentriq, plus nab-paclitaxel, significantly reduced the risk of disease worsening or death (PFS) by 40% compared with nab-paclitaxel alone (median PFS=7.4 vs.