microRNA called miR-142 involved in the process by which the immature cells in the bone marrow give rise to all the types of blood cells, including immune cells and the oxygen-bearing red blood cells


Reporter: Aviva Lev-Ari, PhD, RN






Master Key




Hornstein group

Dr. Elik Chapnik, Natali Rivkin and Dr. Eran Hornstein
It takes only a tiny key to open a door wide or set large machinery in motion. Dr. Eran Hornstein of the Weizmann Institute’s Molecular Genetics Department and his team recently discovered such a key – one that unlocks the cellular machinery for producing mature blood cells. That key is a minuscule, hairpin-shaped RNA belonging to a class of RNA strands so small they had long been ignored. Even now, these so-called microRNAs are too often thought to be secondary to the cell’s major processes. The new findings suggest that microRNAs can also be master keys, putting several vital processes into motion at once.
In collaboration with Prof. Steffen Jung of the Immunology Department and his coworkers Dr. Elik Chapnik, Natali Rivkin and Dr. Alexander Mildner, Hornstein discovered that a microRNA called miR-142 was involved in the process by which the immature cells in the bone marrow give rise to all the types of blood cells, including immune cells and the oxygen-bearing red blood cells. In fact, an early hint for the importance of this microRNA had been documented years earlier, in 1989, as it plays a role in a type of B-cell leukemia. But back then, before the era of genomics and before the microRNA revolution, it was thought to be a protein-coding gene.


wt megakaryocyte

Wild type megakaryocyte
The Weizmann researchers looked at a broad lineage of myeloid cells – a group that includes the red blood cells and the platelets that make our blood clot. They were looking for cells in which miR-142 is instrumental, and that could provide a clear insight into its function. Their initial analysis pointed to megakaryocytes as the ideal experimental model.
Megakaryocytes are very large cells in the bone marrow that generate platelets by budding off bits of their internal cytoplasm. The development of megakaryocytes and their ability to function as they mature depends on a strong, malleable internal structure – the cytoskeleton. In a series of experiments on mouse megakaryocytes, the researchers found that miR-142 is essential to the proper formation of the primary building material of the cytoskeleton – actin fibers. When miR-142 activity was halted, the production of actin was deregulated, and the megakaryocytes were not able to mature and produce platelets.
KO blood cell

Megakaryocyte in which the microRNA mir-142 has been knocked out
Using a large array of techniques in their labs, the researchers were able to reveal the precise activities of miR-142. Their findings, which were recently published ineLife, show that miR-142 is, indeed, a master key that turns on and off a number of different cellular processes; these are crucial to actin production and regulation. To put it another way, microRNA-142 is a “hub” in the cellular network of pathways that keeps the cell growing, dividing, developing and functioning.
According to Hornstein, the impact of microRNA-142 and its mechanism may even go all the way back to the first blood cells in the embryo. In addition, miR-142 malfunctions are likely to show up in certain clotting disorders; but the findings hint that the same miRNA gene may be involved in any number of other blood diseases. Hornstein: “This model for blood cell development is very informative and fruitful. Together with Jung we have already characterized four different cell types in which this miRNA is influential, which is very exciting.”
The implications are clear for microRNA research, says Hornstein, helping cast microRNA in a new light: they can no longer be seen as mere helper molecules that “fine-tune” the cellular pathways; they are also key players with the power to direct the development of the cell.
Dr. Eran Hornstein’s research is supported by the Kekst Family Institute for Medical Genetics; the David and Fela Shapell Family Center for Genetic Disorders Research; the Crown Human Genome Center; the Yeda Sela Center; the Nella and Leon Benoziyo Center for Neurological Diseases; the Y. Leon Benoziyo Institute for Molecular Medicine; the Helen and Martin Kimmel Institute for Stem Cell Research; the Nathan, Shirley, Philip and Charlene Vener New Scientist Fund; the Julius and Ray Charlestein Foundation; the Celia Benattar Memorial Fund for Juvenile Diabetes; the Wolfson Family Charitable Trust; the Legacy Heritage Fund; the Adelis Foundation; the Minna-James-Heineman Stiftung; Dr. Sidney Brenner and Friends; Maria Halphen, France; and the estate of Fannie Sherr. Dr. Hornstein is the incumbent of the Helen and Milton A. Kimmelman Career Development Chair.

Prof. Steffen Jung’s research is supported by the Leir Charitable Foundations; the Leona M. and Harry B. Helmsley Charitable Trust; the Maurice and Vivienne Wohl Biology Endowment; the Adelis Foundation; Lord David Alliance, CBE; the Wolfson Family Charitable Trust; the estate of Olga Klein Astrachan; and the European Research Council.



Pain Management Drug Market: Insight Pharma Reports

Reporter: Aviva Lev-Ari, PhD, RN


Announcement by

Lisa Scimemi, MBE, MSM


Insight Pharma Reports

250 First Avenue, Suite 300

Needham, MA 02494

I wanted to make you aware of these new reports available from


  • Global Pain Management Devices Market 2014-2018
  • Chronic Pain – Pipeline Review
  • Global Pain Management Drugs Market 2014-2018
  • Cancer Pain – Pipeline Review
  • Acute Pain Global Clinical Trials Review
  • Pain Management Therapeutics Market to 2019
  • Inflammatory Pain – Pipeline Review


All these reports are available thru Insight Pharma Reports.  If you are looking for a specific topic not

listed above, contact us and we can search our network of publishers for a report on the topic are you

are looking for.


If you have any questions, or would like to reserve your copy of one of these reports, contact me today.


Thank you.


Lisa Scimemi, MBE, MSM


Insight Pharma Reports

250 First Avenue, Suite 300

Needham, MA 02494



Dompe’ Receives FDA orphan drug designation for rhNGF in the treatment of Neurotrophic Keratitis (NK).

Reporter: Stephen J Williams, PhD


The U.S. FDA granted Dompe’ an orphan drug designation for rhNGF (recombinant human nerve growth factor) in the treatment of Neurotrophic Keratitis (NK).

Neurotrophic Keratitis (NK) is a rare, degenerative corneal disease caused by an impairment of corneal innervation (the distribution or supply of nerves), leading to a decrease or absence of corneal sensation and dysfunction of the corneal epithelium and abnormal corneal epithelial healing. The development of persistent epithelial defects or corneal ulcers can result in vision loss.

Severe NK is consistently recognized by clinicians as a serious condition lacking a highly effective treatment option.

The epidemiology of NK has not been well-defined. The estimated prevalence of patients with moderate-to-severe NK (stage 2-3) is less than 1 person in 5,000 globally.

Clinical trials in the U.S. are expected to begin in the next few months in leading research centers.

Dompé will be present at the American Association of Ophthalmology Annual meeting (Chicago, October 18-21). Currently, the enrollment is ongoing for the company’s Phase II trial with rhNGF in the treatment of NK.
Background – Dompé and its R&D

  • Dompé is a leading Italian biopharmaceutical company (with headquarters in Milan) committed to the development of innovative treatment solutions for rare, often orphan, diseases that have a high social impact, in areas where unmet treatment needs still exist.
  • The Company focuses its R&D activities in diabetes, ophthalmology, oncology and organ transplants.
  • The R&D activities are carried out in the Dompé biotech plant located in L’Aquila (Abruzzo), which has an internationally recognized expertise in the field of rare diseases.  
  • This year (2014), Dompé opened an office in New York, staffed with scientists and R&D teams in order to carry out and coordinate the scientific activities in the U.S.


Dompé commitment in ophthalmology – rhNGF

  • In ophthalmology, Dompé is promoting the research and development of Nerve Growth Factor (NGF), a soluble protein that stimulates the growth, maintenance and survival of neurons, whose discovery led to Prof. Rita Levi Montalcini being awarded the Nobel Prize in 1986.
  • Recombinant human Nerve Growth Factor (rhNGF) has been studied and produced exclusively at Dompé’s production site in L’Aquila, Italy, and is undergoing an international Phase II trial, called “REPARO”, to evaluate its efficacy and safety in the treatment of Neurotrophic Keratitis, a rare orphan disease. The trial is being conducted in 39 centers and nine European countries.

The medicine recently has been designated an orphan drug for the treatment of Retinitis Pigmentosa (RP), a severe, genetic rare disease that can lead to blindness for which there is currently no treatment available. A clinical trial in the EU, involving patients with RP, started in the first quarter of 2014 with the enrolment of the first patient.


From: Gail Thornton <gailsthornton@yahoo.com>
Reply-To: Gail Thornton <gailsthornton@yahoo.com>
Date: Wed, 23 Jul 2014 07:02:05 -0700
To: Aviva Lev-Ari <avivalev-ari@alum.berkeley.edu>
Subject: Dompe’ Receives FDA orphan drug designation for rhNGF

Originally posted on horovits:

Things definitely change fast in the landscape of the Internet of Things. On my last blog post less than 2 weeks ago I discussed standardization efforts in IoT and covered the announcement of a new consortium called Open Interconnect Consortium (OIC), led by Samsung, Intel, Dell and others.

And just a week later we got the new heavy gun in the field: Google announced, through its recently acquired company Nest, a new industry group called Thread, together with Samsung, ARM Holdings and others, to define the communications standard for the smart home. The new standard is said to solve reliability, security, power and compatibility issues for connecting products around the home.


This announcement joins Microsoft’s announcement from beginning of this month about joining AllSeen Alliance as the 51st member, which was followed by last week’s announcement of 7 other new members, making AllSeen Alliance 58 members strong to date (on my last…

View original 172 more words



News in Exploration of the Biological Causes of Mental Illness: Potential for New Treatments

Reporter: Aviva Lev-Ari, PhD,RN

Broad’s Stanley Center for Psychiatric Genome Research: Ted Stanley Pledges $650M

Initially opened with a gift from Stanley and his late wife in 2007, the Broad’s Stanley Center has already made progress in identifying genetic risk factors for schizophrenia and bipolar disorder and investigating therapeutic efforts based on those discoveries. This week researchers from Broad and other institutes published a GWAS analysis inNature that identified more than 100 regions of DNA associated with schizophrenia.

“Ten years ago, finding the biological causes of psychiatric disorders was like trying to climb a wall with no footholds,” Stanley Center Director Steven Hyman said in a statement. “But in the last few years, we’ve turned this featureless landscape into something we can exploit. If this is a wall, we’ve put toeholds into it. Now, we have to start climbing.”




The Nature paper1 was produced by the Psychiatric Genomics Consortium (PGC) — a collaboration of more than 80 institutions, including the Broad Institute. Hundreds of researchers from the PGC pooled samples from more than 150,000 people, of whom 36,989 had been diagnosed with schizophrenia. This enormous sample size enabled them to spot 108 genetic locations, or loci, where the DNA sequence in people with schizophrenia tends to differ from the sequence in people without the disease. “This paper is in some ways proof that genomics can succeed,” Hyman says.


“This is a pretty exciting moment in the history of this field,” agrees Thomas Insel, director of the National Institute of Mental Health (NIMH) in Bethesda, Maryland, who was not involved in the study.





Biological insights from 108 schizophrenia-associated genetic loci

Ripke, S. et alNature http://dx.doi.org/10.1038/nature13595 (2014).


Nature (2014) doi:10.1038/nature13595
Published online 22 July 2014



Schizophrenia is a highly heritable disorder. Genetic risk is conferred by a large number of alleles, including common alleles of small effect that might be detected by genome-wide association studies. Here we report a multi-stage schizophrenia genome-wide association study of up to 36,989 cases and 113,075 controls. We identify 128 independent associations spanning 108 conservatively defined loci that meet genome-wide significance, 83 of which have not been previously reported. Associations were enriched among genes expressed in brain, providing biological plausibility for the findings. Many findings have the potential to provide entirely new insights into aetiology, but associations at DRD2 and several genes involved in glutamatergic neurotransmission highlight molecules of known and potential therapeutic relevance to schizophrenia, and are consistent with leading pathophysiological hypotheses. Independent of genes expressed in brain, associations were enriched among genes expressed in tissues that have important roles in immunity, providing support for the speculated link between the immune system and schizophrenia.



In the largest (to our knowledge) molecular genetic study of schizophrenia, or indeed of any neuropsychiatric disorder, ever conducted, we demonstrate the power of GWAS to identify large numbers of risk loci. We show that the use of alternative ascertainment and diagnostic schemes designed to rapidly increase sample size does not inevitably introduce a crippling degree of heterogeneity. That this is true for a phenotype like schizophrenia, in which there are no biomarkers or supportive diagnostic tests, provides grounds to be optimistic that this approach can be successfully applied to GWAS of other clinically defined disorders.

We further show that the associations are not randomly distributed across genes of all classes and function; rather they converge upon genes that are expressed in certain tissues and cellular types. The findings include molecules that are the current, or the most promising, targets for therapeutics, and point to systems that align with the predominant aetiological hypotheses of the disorder. This suggests that the many novel findings we report also provide an aetiologically relevant foundation for mechanistic and treatment development studies. We also find overlap between genes affected by rare variants in schizophrenia and those within GWAS loci, and broad convergence in the functions of some of the clusters of genes implicated by both sets of genetic variants, particularly genes related to abnormal glutamatergic synaptic and calcium channel function. How variation in these genes impact function to increase risk for schizophrenia cannot be answered by genetics, but the overlap strongly suggests that common and rare variant studies are complementary rather than antagonistic, and that mechanistic studies driven by rare genetic variation will be informative for schizophrenia.




Manhattan plot showing schizophrenia associations.

Manhattan plot of the discovery genome-wide association meta-analysis of 49 case control samples (34,241 cases and 45,604 controls) and 3 family based association studies (1,235 parent affected-offspring trios). The x axis is chromosomal position and the y axis is the significance (–log10 P; 2-tailed) of association derived by logistic regression. The red line shows the genome-wide significance level (5×10−8). SNPs in green are in linkage disequilibrium with the index SNPs (diamonds) which represent independent genome-wide significant associations.




Biological insights from 108 schizophrenia-associated genetic loci


Schizophrenia Working Group of the Psychiatric Genomics Consortium


Nature (2014) doi:10.1038/nature13595



In vitro Models of Tumor Microenvironment for New Cancer Target and Drug Discovery, 11/17 – 11/19/2014, Hyatt Boston Harbor

Reporter: Aviva Lev-Ari, PhD, RN


On 7/21/2014 Cambridge Healthtech Institute Announced:

Cambridge Healthtech Institute, 250 First Avenue, Suite 300, Needham, MA 02494, http://www.healthtech.com



Traditional drug screening relies on monolayer cell culture, which is not always predictive of natural physiological state. This is especially problematic in cancer drug discovery, where simple cell cultures are not predictive of complex tumor microenvironment that consists of various cell types that interact in 3-dimensional structures. As the cost of drug development rises, there is increasing pressure for more predictive in vitro models for functional analysis and compound characterization. Cambridge Healthtech Institute’s Second Annual Physiologically-Relevant Cellular Tumor Models for Drug Discovery meeting will focus on the latest advances in 3D cellular tumor models and complex co-culture systems for functional analysis studies and compound screening/characterization.



An All-Human Microphysiologic Liver System for Carcinoma Metastasis

Alan H. Wells, M.D., D.M.Sc., Vice Chair and Thomas J. Gill III Professor, Pathology, University of Pittsburgh



New Tricks for Spheroids: Mimicking Stromal Interactions, Investigating Nanoparticle Drug Delivery, and Modeling Resection

Mark Grinstaff, Ph.D., Professor, Chemistry, Boston University

Functional Analysis of Therapeutic Antibodies and Antigens Using ex vivo Tumor Spheroids

Mitchell Ho, Ph.D., Chief, Antibody Therapy Section, Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health



High-Throughput Compatible Co-Spheroid Model Analyzing Compound Effects on Both Tumor and Stroma Cells

Jan E. Ehlert, Ph.D., Head, Cellular Drug Discovery, ProQinase GmbH

Sponsored by: ProQinase GmbH

Additional sponsorship opportunities available. Contact Ilana Quigley at iquigley@healthtech.com.HIGH-CONTENT ANALYSIS OF TUMOR SPHEROID MODELS

Drug Discovery and Development of Novel Anticancer Agents: Applications of Novel 3D Multicellular Tumor Spheroid Models

Daniel V. LaBarbera, Ph.D., Assistant Professor, Drug Discovery and Medicinal Chemistry, The Skaggs School of Pharmacy and Pharmaceutical Sciences, The University of Colorado

Novel Stromal Targets that Support Tumor Spheroid Formation

Shane R. Horman, Ph.D., Research Investigator, Advanced Assay Group, Genomics Institute of the Novartis Research Foundation

Developing Biodynamic Screening Assays for 3D Live-Tissue Models

David Nolte, Ph.D., Professor, Physics, Purdue University; President, Animated Dynamics, Inc.



Targeted Electric Field Therapy Development in 3D Models of the Heterogeneous Glioma Microenvironment

Scott S. Verbridge, Ph.D., Assistant Professor, School of Biomedical Engineering and Sciences, Virginia Tech – Wake Forest University

Targeting Physical and Stromal Determinants of Tumor Heterogeneity in Bioengineered 3D Models

Imran Rizvi, Ph.D., Instructor, Medicine and Dermatology, Harvard Medical School; Associate Bioengineer, Brigham and Women’s Hospital; Assistant, Biomedical Engineering, Wellman Center for Photomedicine, Massachusetts General Hospital

Hydrogel Co-Culture Systems for Growing Patient-Derived Xenografts: Use in Selective Drug Screening

Mary C. Farach-Carson, Ph.D., Ralph and Dorothy Looney Professor, Biochemistry and Cell Biology; Scientific Director, BioScience Research Collaborative, Rice University

Human Stroma-Derived Extracellular Matrices: 3D ECM Physiological Systems

Edna Cukierman, Ph.D., Associate Professor, Cancer Biology, Fox Chase Cancer Center


Microfluidic Models with Microvascular Networks to Study Metastatic Disease

Roger D. Kamm, Ph.D., Cecil and Ida Green Distinguished Professor, Biological and Mechanical Engineering, MIT

Monitoring Extravascular Migratory Metastasis of Angiotropic Cancer Cells Using a 3D in vitro Co-Culture System

Claire Lugassy, M.D., Research Associate Professor, Pathology and Lab Medicine, UCLA School of Medicine; Member, Jonsson Comprehensive Cancer Center

Using Block Cell Printing to Develop Single Cell Arrays for Drug Screening

Lidong Qin, Ph.D., Associate Member, Nanomedicine, Methodist Hospital Research Institute; Assistant Professor, Cell and Developmental Biology, Weill Cornell Medical College




Stem Cell Models for Drug Discovery

Monday Evening, November 17 | 6:30-9:30 pm


Anne G. Bang, Ph.D., Director, Cell Biology, Prebys Center, Sanford-Burnham Medical Research Institute

Pamela J. Hornby, Ph.D., Senior Scientific Director and Research Fellow, Cardiovascular and Metabolic Disease, Translational Models, Janssen Pharmaceutical Companies of Johnson & Johnson

Wei Zheng, Ph.D., Group Leader, National Center for Advancing Translational Sciences, National Institutes of Health

Expert ThinkTank: How to Meet the Need for Physiologically-Relevant Assays?

Tuesday Evening, November 18 | 6:00-9:00 pm


Lisa Minor, Ph.D., President, In Vitro Strategies, LLC


Beverley Isherwood, Ph.D., Team Leader, AstraZeneca R&D

Michael Jackson, Ph.D., Senior Vice President, Drug Discovery and Development, Conrad Prebys Center for Chemical Genomics, Sanford-Burnham Medical Research Institute (tentative)

Jean-Louis Klein, Ph.D., Principal Scientist, Target and Pathway Validation, Platform Technology and Science, GlaxoSmithKline

Caroline Shamu, Ph.D., Director, ICCB-Longwood Screening Facility and Assistant Professor, Harvard Medical School

D. Lansing Taylor, Ph.D., Director, University of Pittsburgh Drug Discovery Institute and Allegheny Foundation; Professor, Computational and Systems Biology, University of Pittsburgh

Scott S. Verbridge, Ph.D., Assistant Professor, School of Biomedical Engineering and Sciences, Virginia Tech – Wake Forest University

Soft Tissue Transponder for Radiotherapy and Radiosurgery Treatments for Cancer got FDA Approval

Reporter: Aviva Lev-Ari, PhD, RN

Varian Medical Systems ($VAR) scored FDA 510(k) clearance for its soft tissue transponder for radiotherapy and radiosurgery treatments


FDA clears Varian soft tissue transponder to treat cancer

Varian Medical Systems’ Calypso soft tissue Beacon transponder–Courtesy of Varian

Varian Medical Systems ($VAR) scored FDA 510(k) clearance for its soft tissue transponder for radiotherapy and radiosurgery treatments.

The Palo Alto, CA-based company’s Calypso soft tissue Beacon transponders are implanted in soft tissue throughout the body, allowing physicians to target high energy treatment beam radiation at tumors without damaging surrounding tissue. The grain-sized device includes a real-time GPS monitoring system that continuously tracks and monitors the position of transponders during radiosurgery.

An earlier version of the product was cleared for use in the prostate and prostatic bed, but the new indication expands the device’s applications for other types of cancer, the company said in a statement. Varian plans to release the transponders toward the end of this year, and expects a full commercial roll-out in 2015.

“We’re pleased to be able to make the system available to clinicians who want to use it more broadly, not just for conventional radiotherapy but for some of the newer approaches, like stereotactic body radiotherapy (SBRT), which involves delivering higher radiation doses very quickly,” Andrea Morgan, Calypso product manager said in a statement. “For treatments like that, accurate targeting is essential, and the new Calypso transponders have an important role to play.”

The FDA nod bodes well for Varian, as the company struggles to recover from a disappointing second quarter. The devicemaker saw its net earnings fall nearly 18% in Q2, with profits of $92.7 million down from $112.8 million the same period last year. Revenue increased 1% to $779 million, primarily due to a 4% jump in oncology sales and a slight uptick in imaging components.

Regulatory blessings also help Varian forge ahead in its emerging markets, where the company sees strong demand for its oncology and medical imaging products. Last year, Varian built its first Asian subsidiary in South Korea, giving it an expanded market for its cancer-treating radiotherapy devices and imaging equipment. In January, the company renewed a three-year, $515 billion deal withToshiba Medical Systems to supply medical imaging components. The companies originally charted the deal in January 2011 for an estimated $450 billion.

Varian Medical Systems

Varian Medical Systems, Inc., of Palo Alto, California, is the world’s leading manufacturer of medical devices and software for treating cancer and other medical conditions with radiotherapy, radiosurgery, and brachytherapy. The company supplies informatics software for managing comprehensive cancer clinics, radiotherapy centers and medical oncology practices. Varian is a premier supplier of tubes, digital detectors, and image processing workstations for X-ray imaging in medical, scientific, and industrial applications and also supplies high-energy X-ray devices for cargo screening and non-destructive testing applications.  Varian Medical Systems employs approximately 6500 people who are located at manufacturing sites in North America, Europe, and China and approximately 70 sales and support offices around the world. For more information, visit http://www.varian.com or follow us on Twitter .


- read the release

Related Articles:
Varian’s profits slip as revenue ticks up slightly
Varian Medical pays $35M to settle Pitt patent spat
Varian touts emerging markets as looming Medicare changes take a toll
Varian, Toshiba announce a $515M medical imaging deal
Korean government ramps up plans to boost medical equipment exports




Get every new post delivered to your Inbox.

Join 1,375 other followers