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Archive - Nov 2015

November 8th

Silica Nanoparticles Containing Moxifloxacin, and with pH-Sensitive Nanovalves, Deliver Antibiotic Directly within Macrophages and Vastly Improve Drug’s Effectiveness Against Pneumonic Tularemia Caused by Francisella tularensis

Scientists from the California NanoSystems Institute at UCLA have developed a nanoparticle delivery system for the antibiotic moxifloxacin that vastly improves the drug’s effectiveness against pneumonic tularemia, a type of pneumonia caused by inhalation of the bacterium Francisella tularensis. The study, which was published online on October 5, 2015 in the journal ACS Nano, shows how the nanoparticle system targets the precise cells infected by the bacteria and maximizes the amount of drug delivered to those cells. The article is titled “Mesoporous Silica Nanoparticles with pH-Sensitive Nanovalves for Delivery of Moxifloxacin Provide Improved Treatment of Lethal Pneumonic Tularemia.” Jeffrey Zink, Ph.D., Distinguished Professor of Chemistry and Biochemistry and a senior author on the study, developed the mesoporous silica nanoparticles used for drug delivery. Dr. Zink and his research team conducted an exhaustive process to find the best particle for the job. “The nanoparticles are full of deep empty pores,” Dr. Zink said. “We place the particles in drug solution overnight, filling the pores with drug molecules. We then block the pore openings on the nanoparticle’s surface with molecules called nanovalves, sealing the drug inside the nanoparticle.” When the drug-bearing nanoparticles are injected into the infected animal, in this case a mouse, the drug stays in the nanoparticles until they reach their target: white blood cells called macrophages. Macrophages ingest nanoparticles into compartments that have an acidic environment. The nanovalves, which are designed to open in response to the more acidic surroundings, then release the drug.

Rapid-Detection, Point-of-Care Saliva Test for Ebola Deployed in Mobile, Suitcase-Sized Labs in Senegal & Guinea

A rapid-detection Ebola test developed by an international team of scientists, including a University of Stirling, Scotland virologist has been deployed following a highly effective pilot project. Manfred Weidmann, Ph.D., from the University's School of Natural Sciences, was part of a Wellcome Trust project led by the Pasteur Institute of Dakar. Together, the scientists developed a sophisticated, point-of-care saliva test, all contained within a suitcase-sized mobile laboratory. Three mobile labs have now been deployed in Senegal and Guinea, and a test evaluation of 928 samples showed that the new test performs exceptionally well under field conditions. "There are more than 25 laboratories in West Africa and everyone is using different tests," said Dr. Weidmann. "Ours, which uses a method called recombinase polymerase amplification, was compared to two other tests and results show it can be reliably used without the need for a confirmatory test, and it appears to outperform a widely used WHO recommended test.”"There has been a huge push for robotic testing systems, but they are difficult to establish and expensive to maintain. Our project has successfully developed and deployed a low-cost mobile laboratory, using a rapid, highly sensitive and specific assay that can be stored at room temperature and operated by local teams with its own energy supply." Dr. Weidmann has also developed a range of assays to detect other mosquito-borne viruses, such as Dengue virus and Rift Valley Fever virus. He added: "Mosquito-borne viruses can affect high numbers of people much faster than Ebola, and outbreaks of Dengue virus and Rift Valley Fever virus have recently erupted in West-Africa. The system represents real progress in the quest to take the laboratory into the field.

$1.5 Million Awarded for Oxford Research to Develop Brain-Targeted, Systemically-Administered Exosomes That Will Cross Blood-Brain Barrier to Deliver Gene-Silencing Drugs to Inhibit Expression of Mutant Huntington’s Disease Gene in Brain

Matthew Wood (photo), Ph.D., Professor of Neuroscience at the University of Oxford, has been granted an award of £1,008,110 ($1,517,155) from the UK’s Medical Research Council (MRC) for a three-year research project (September 2015-August 2018) intended to develop an systemically-administered, exosome-based, gene-silencing therapy for Huntington’s disease (HD). In the project description (see link below), it is noted that, although therapeutic compounds are being actively developed to treat HD, the delivery of these drugs into the brain is a major impediment to the successful development of these candidate drugs into effective treatments. Consequently, in the newly funded project, Dr. Wood and his Oxford team intend to develop what they term “an entirely new solution” to this major problem. Over the course of 36 months (September 2015 to August 2018), the researchers will attempt to develop a new treatment that can switch off the mutant huntingtin (HTT) gene, and that can successfully cross the blood-brain barrier (BBB) to enter the brain using small, natural sub-cellular particles called exosomes. Exosomes are fat-encapsulated, sub-cellular particles (vesicles) that are generated naturally by all cells of the body and that Dr. Wood and his team have previously exploited for the delivery of drugs into the brain by modifying the exosomes in such a way that they display small molecules on their surface that allow them to home into the brain following their injection into a vein in the body. Perfecting this systemically-administered, exosome-based, brain-targeted drug delivery approach will open the door to testing many compounds that have been proven potentially capable of reducing the levels of the mutant HTT protein that is coded for by the mutant HTT gene in HD.

November 7th

Odometer Neurons: Study of Treadmill-Running Rats Shows That Brain’s Grid Cells Can Encode Time and Distance, As Well As Location in Space

Animals navigate by calculating their current position based on how long and how far they have traveled and a new study on treadmill-running rats reveals how: neurons called grid cells integrate information about time and distance to support memory and spatial navigation, even in the absence of visual landmarks. The findings, published in an open-access article in the November 4, 2015 issue of Neuron, challenge currently held views of the role of grid cells in the brain. The article is titled “During Running in Place, Grid Cells Integrate Elapsed Time and Distance Run.” "Space and time are ever-present dimensions by which events can be organized in memory," says senior study author Howard Eichenbaum, Ph.D., a psychologist and neuroscientist at Boston University. "These findings support the view that memory evolved as a common function in mammals using circuits that organize events in space, time, and potentially many other dimensions of experience." Past research has shown that grid cells receive information from other cells about the direction traveled. But until now, there was no direct evidence showing that grid cells signal distance or time, leaving the role of these variables in path integration merely speculative. In the new study, Dr. Eichenbaum and first author Benjamin Kraus, Ph.D., also of Boston University, and colleagues, addressed this question by placing rats on treadmills while recording the activity of grid cells. The researchers kept either the run duration or run distance fixed, while varying the speed, in order to disentangle the influence of these factors on cell firing. During treadmill running, 92% of grid cells fired at specific moments or distances while the rats ran in place.

Lupski-Led Analysis of Rare Genetic Variants (SNVs and CNVs) in Mendelian Neurogenetic Disorders Identifies Genes That Affect Brain Structure & Function

Like the delicate strokes of the painter’s brush, genes and the epigenetics that regulate them guide the formation of the complicated architecture of the human brain. The result is a marvel of biology, able to learn and to create, while controlling the most basic functions of the body. However, when the genes do not work well or the epigenetic mechanisms are out of alignment, the result is often a devastating genetic disorder, sometimes coupled with a brain malformation. In a news study published in the November 4, 2015 issue of Neuron, an international team of researchers led by James Lupski (photo), M.D., Ph.D., at the Baylor College of Medicine in Houston, Texas, and including a large group of Turkish medical professionals, evaluated the genetics underlying such brain disorders and malformations. The Neuron article is titled “Genes that Affect Brain Structure and Function Identified by Rare Variant Analyses of Mendelian Neurologic Disease.” In their newly reported work, the researchers found variants of genes already known to cause brain disorders and malformations, and they also identified new mutations in genes not previously known to be involved in such problems. In addition, they identified structural deviations such as the duplications or deletions known as copy number variations (CNVs) in different chromosomes. “Human brain development is a precisely orchestrated process requiring multiple genetic and epigenetic events,” said Dr. Lupski, the Cullen Professor of Molecular and Human Genetics at Baylor College of Medicine and the senior and corresponding author of the Neuron article. Dr.

Whole Genome Sequencing of All 14 Known Species of Malassezia Fungi Identifies Multiple Targets for Potential Treatments of Dandruff, Seborrheic Dermatitis, Eczema, and a Form of Skin Cancer

An international team of scientists, led by researchers from A*STAR’s Genome Institute of Singapore (GIS), Institute of Medical Biology (IMB), and Bioinformatics Institute (BII), and Proctor & Gamble, has completed the first comprehensive genomic and biologic study of all known species of Malassezia, one of the top skin disease-causing microbes. The breakthrough study identified multiple potential targets for treating diseases such as seborrheic dermatitis, eczema, and dandruff, all of which can be caused by Malassezia. Malassezia is also associated with skin cancer, the sixth most common cancer in males and the seventh in females in Singapore. These findings improve our understanding of the human skin microbiome, with significant implications for dermatology and immunology. The new study was published online on November 5, 2015 in the November issue of the open-access journal PLOS Genetics, under the title “Genus-Wide Comparative Genomics of Malassezia Delineates Its Phylogeny, Physiology, and Niche Adaptation on Human Skin.” Malassezia is a type of fungus found on the skin of all birds and warm-blooded mammals, including humans. Often, Malassezia simply forms part of our normal skin flora, but, for unknown reasons, it sometimes causes disease. In their article abstract, the authors noted that “Malassezia is a unique lipophilic genus in class Malasseziomycetes in Ustilaginomycotina, (Basidiomycota, fungi) that otherwise consists almost exclusively of plant pathogens. Malassezia are typically isolated from warm-blooded animals, are dominant members of the human skin mycobiome and are associated with common skin disorders.” Two particular species of Malassezia, namely M. restricta and M. globosa, are present on all human scalps and are responsible for common dandruff and seborrheic dermatitis.

November 6th

MGH/Harvard-Led Team Reports First-Ever Successful Systemic Treatment of Recurrent, BRAF-Mutant Brain Tumor (Craniopharyngioma) with Monoclonal Antibody BRAF Inhibitor Dabrafinib

A team led by Massachusetts General Hospital (MGH) investigators has reported the first successful use of a targeted therapy drug to treat a patient with a debilitating, recurrent brain tumor. In a paper published online on October 23, 2015 in the Journal of the National Cancer Institute (JNCI), the researchers report that treatment with the BRAF inhibitor dabrafinib led to shrinkage of a BRAF-mutant craniopharyngioma that had recurred even after four surgical procedures. More than a year after dabrafinib treatment, which was followed by surgery and radiation therapy, the patient's tumor has not recurred. The article is titled “Dramatic Response of BRAF V600E Mutant Papillary Craniopharyngioma to Targeted Therapy.” "This is the first time that a systemic therapy has shown efficacy against this type of tumor," says Priscilla Brastianos (photo), M.D., co-lead author of the JNCI report. Dr. Brastianos is Director, Central Nervous System Metastasis Program. Massachusetts General Hospital. Harvard Medical School. She is also Instructor of Medicine, Harvard Medical School. "This has the potential of completely changing the management of papillary craniopharyngiomas, which can cause lifelong problems for patients - including visual defects, impaired intellectual function, and pituitary and other hormonal dysfunction." Craniopharyngiomas are pituitary tumors that, while technically benign, can cause serious problems because of their location near critical structures, such as optic and other cranial nerves and the hypothalamus. Not only does the growing tumor compromise neurological and hormonal functions by impinging on these structures, but treatment by surgical removal or radiation therapy can produce the same symptoms by damaging adjacent tissues.

Capricor Therapeutics to Present 6-Month Safety & Exploratory Efficiency Results from Ongoing Phase I DYNAMIC Clinical Trial of Cardiosphere-Derived-Cell (CDC) Therapy (CAP-1002) for Advanced Heart Failure on Monday, November 9

Capricor Therapeutics, Inc., (NASDAQ: CAPR), a biotechnology company focused on the discovery, development, and commercialization of first-in-class therapeutics, announced, on Friday, November 6, 2015, that results will be presented from its ongoing Phase I DYNAMIC (Dilated Cardiomyopathy Intervention with Allogeneic Myocardially Regenerative Cells) clinical trial evaluating CAP-1002 in patients with advanced heart failure. The data will be presented in a poster to be delivered at the 2015 American Heart Association (AHA) Scientific Sessions taking place November 7-11, 2015 in Orlando, Florida. The poster is titled “Dilated Cardiomyopathy Intervention with Allogeneic Myocardially Regenerative Cells (DYNAMIC): Six Month Safety and Exploratory Efficacy Results,” and it will be presented on Monday, November 9, 2015, 5:30 - 6:45 pm ET in Poster Hall, A2, BS, in the “APS.06.02. Stem/Progenitor Cells II” session (Poster Number: M 104). CAP-1002 is Capricor's lead investigational allogeneic, cardiosphere-derived-cell (CDC) therapy. The Phase I DYNAMIC trial is evaluating CDCs (CAP-1002) ( in patients with advanced heart failure. The trial enrolled 14 patients with either ischemic or non-ischemic dilated cardiomyopathy with left ventricular ejection fraction (LVEF) of 35% or below and New York Heart Association (NYHA) Class III or Ambulatory Class IV heart failure. Suitable patients underwent sequential intracoronary infusion of CAP-1002 in up to three coronary territories. The primary safety endpoints were assessed at the 1-month visit. Other safety and exploratory efficacy endpoints, including ejection fraction, ventricular volumes, and a six-minute walk test were evaluated at 6 months and will be evaluated at a 12-month follow-up.

Worrisome Dung Beetle Decline in Mediterranean; Eco-Important Beetle’s Olfactory, Locomotor, & Reproductive Capacities Damaged by Low Doses of Ivermectin, Anti-Parasitic Drug Commonly Adminstered to Livestock

Research led by the University of Alicante's Ibero-American Centre for Biodiversity (WHERE) in Spain shows the adverse effects of an anti-parasitic drug (ivermectin), commonly administered prophylactically to livestock, on populations of a key dung beetle in Mediterranean ecosystems. A multidisciplinary research team, made up of researchers from the Spanish universities of Alicante, Jaen and Granada, the French Universities of Montpellier and Paul-Valéry Montpellier, the CSIC's National Museum of Natural Sciences, and the IUCN Centre for Mediterranean Cooperation, has analyzed the impact of ivermectin on Scarabaeus cicatricosus populations in the Mediterranean region. Led by José R. Verdú, Ph.D., from the Ibero-American Centre for Biodiversity (CIBIO) at the Universidad de Alicante, this research shows that arthropods that ingest this substance, even in low doses, become unable to interact with their surroundings because the drug affects both their olfactory and locomotor capacity. This fact may explain the population decline observed for this dung beetle. The open-access article reporting this finding, “Low Doses of Ivermectin Cause Sensory and Musculoskeletal Disorders in Dung Beetles,” was published online on September 9, 2015 in Scientific Reports. Ivermectin is a very effective anti-parasitic drug that has been used as a preventative in livestock since its discovery in 1981. Since then, the use of ivermectin use has increased exponentially to become a standard drug in the treatment and prevention of common parasites, including in human beings. The drug is considered by the World Health Organization (WHO) to be as an essential medication. Dr. Verdú points out that, although this drug has proven very effective, its widespread use comes at a price.

Exosome Diagnostics to Present New Data on Plasma EGFR Mutation Detection Using a Combined Exosomal RNA and Circulating Tumor DNA Approach & on ID of Novel Exosome mRNA Signature of Ipilimumab Response in Metastastic Melanoma Patients

Exosome Diagnostics, Inc., a developer of revolutionary, biofluid-based molecular diagnostics, announced on November 6, 2015 that the company will present two posters at the 26th AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics, taking place November 5-9 at the Hynes Convention Center in Boston, Massachusetts. The first poster contains new data on the company’s exosomal RNA (exoRNA) plus cell-free (cfDNA) liquid biopsy panel for solid tumors. According to Exosome Diagnostics, this data demonstrates superior detection of activating and acquired resistance mutations to EGFR therapy in patients with non-small cell lung cancer (NSCLC) versus a cfDNA-only approach. The title of this poster is “Plasma EGFR Mutation Detection Using a Combined Exosomal RNA and Circulating Tumor DNA Approach in Patients with Acquired Resistance to First-Generation EGFR-TKIs” (#15-A-456-AACR). This poster will be presented on Saturday, November 7, from 12:30 to 3:30 p.m. ET. The second Exosome Diagnostics poster demonstrates the ability of the company’s proprietary exoRNA technology to enrich cancer-specific exosomes in order to more precisely determine tumor-specific gene changes in response to immunotherapy treatment. The title of this second poster is “Early Exosome mRNA Changes Are Associated with Improved Progression-Free Survival of Metastatic Melanoma patients on Ipilimumab: Identification of a Novel Exosome mRNA Signature of Ipilimumab Response” (#LB-C05). This poster will be presented on Sunday, November 8, from 12:30 to 3:30 p.m. ET. The image shows Johan Skog, Ph.D., Chief Scientific Officer and Founding Scientist of Exosome Diagnostics.