Neural Cell News Volume 13.21 | June 5 2019

TOP STORY

mir-17~92 Confers Motor Neuron Subtype Differential Resistance to ALS-Associated Degeneration

Reduced mir-17~92 was accompanied by elevated nuclear PTEN in spinal motor neurons (MNs) of presymptomatic SOD1^G93A mice. Selective dysregulation of the mir-17~92/nuclear PTEN axis in degenerating SOD1^G93A lateral motor column-MNs was confirmed in a double-transgenic embryonic stem cell system and recapitulated in human SOD1^+/L144F-induced pluripotent stem cell-derived MNs. [Cell Stem Cell] Abstract | Graphical Abstract

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Direct Reprogramming of Human Neurons Identifies MARCKSL1 as a Pathogenic Mediator of Valproic Acid-Induced Teratogenicity

Scientists showed that directly reprogrammed neurons, despite their rapid maturation kinetics, could model teratogenic mechanisms that specifically affect early neurodevelopment. They delineated distinct phases of in vitro maturation during reprogramming of human neurons and assessed the cellular phenotypes of valproic acid, a teratogenic drug. [Cell Stem Cell] Abstract | Graphical Abstract

Single-Cell Activity Tracking Reveals that Orbitofrontal Neurons Acquire and Maintain a Long-Term Memory to Guide Behavioral Adaptation

Researchers showed that the orbitofrontal cortex contained several functional clusters of neurons distinctly encoding cue-reward memory representations, with only select responses routed downstream to the ventral tegmental area. Unexpectedly, these representations were stably maintained by the same neurons even after extinction of the cue-reward pairing, and supported behavioral learning and memory. [Nat Neurosci] Abstract

Neuronal Differentiation and Cell-Cycle Programs Mediate Response to BET-Bromodomain Inhibition in MYC-Driven Medulloblastoma

Using a combination of expression profiling, genome-scale CRISPR/Cas9-mediated loss of function and ORF/cDNA driven rescue screens, and cell-based models of spontaneous resistance, the authors identified bHLH/homeobox transcription factors and cell-cycle regulators as key genes mediating BET-bromodomain inhibition’s response and resistance. [Nat Commun] Full Article

Tau Binding Protein CAPON Induces Tau Aggregation and Neurodegeneration

Carboxy-terminal PDZ ligand of neuronal nitric oxide synthase (CAPON) expression induced significantly higher levels of phosphorylated, oligomerized and insoluble tau. In contrast, CAPON deficiency ameliorated Alzheimer’s disease-related pathological phenotypes in a tauopathy model. [Nat Commun] Full Article

ANO1/TMEM16A Regulates Process Maturation in Radial Glial Cells in the Developing Brain

Knockdown of ANO1 suppressed radial glial cell (RGC) process extension and protrusions, whereas ANO1 overexpression stimulated process extension. Among various trophic factors, brain-derived neurotrophic factor (BDNF) activated ANO1, which was required for BDNF-induced process extension in RGCs. [Proc Natl Acad Sci USA] Full Article

Olfactory Sensory Neurons Mediate Ultrarapid Antiviral Immune Responses in a TrkA-Dependent Manner

Scientists report that nasal delivery of rhabdoviruses induced apoptosis in crypt olfactory sensory neurons (OSNs) via the interaction of the OSN TrkA receptor with the viral glycoprotein in teleost fish. This signal resulted in electrical activation of neurons and very rapid proinflammatory responses in the olfactory organ, but dampened inflammation in the olfactory bulb. [Proc Natl Acad Sci USA] Abstract

STRIPAK Members Orchestrate Hippo and Insulin Receptor Signaling to Promote Neural Stem Cell Reactivation

The authors showed that PP2A/microtubule star phosphatase, with its regulatory subunit Widerborst, maintained neural stem cell (NSC) quiescence, preventing premature activation of InR/PI3K/Akt signaling. Conversely, an increase in Mob4 and Cka levels promoted NSC reactivation. [Cell Rep] Full Article | Graphical Abstract

Individual Oligodendrocytes Show Bias for Inhibitory Axons in the Neocortex

Researchers found that different classes of cortical interneurons showed distinct patterns of myelin distribution starting from the onset of myelination, suggesting that oligodendrocytes can recognize the class identity of individual types of interneurons that they target. Notably, they showed that some oligodendrocytes disproportionately myelinate the axons of inhibitory interneurons, whereas others primarily target excitatory axons or show no bias. [Cell Rep] Full Article | Graphical Abstract

Stem Cell-Derived Cranial and Spinal Motor Neurons Reveal Proteostatic Differences between ALS Resistant and Sensitive Motor Neurons

Investigators report that embryonic stem cell (ESC)-derived cranial motor neurons (CrMNs) accumulated less human (h)SOD1 and insoluble p62 than spinal motor neurons (SpMNs) over time. ESC-derived CrMNs had higher proteasome activity to degrade misfolded proteins and were intrinsically more resistant to chemically-induced proteostatic stress than SpMNs. [eLife] Abstract

Malignant Glioma Therapy by Vaccination with Irradiated C6 Cells-Derived Microvesicles Promote an Antitumoral Immune Response

Scientists characterized and evaluated irradiated C6 cells-derived microvesicles as a therapeutic vaccination in C6 malignant glioma. Cultured C6 glioma cells were irradiated by a single dose of 50 Gy to obtain the microvesicles. Subcutaneous implant of C6 cells was made, once the tumor developed 2 cm of diameter, non-irradiated and irradiated C6 cells-derived microvesicles were administered subcutaneously. [Mol Ther] Abstract | Full Article

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Spinal Cord Repair: Advances in Biology and Technology

The authors summarize recent advances in biological and engineering strategies to augment neuroplasticity and/or functional recovery in animal models of spinal cord injury that are pushing toward clinical translation. [Nat Med] Abstract

Perineuronal Nets: Plasticity, Protection, and Therapeutic Potential

The crucial role of perineuronal nets (PNNs) in plasticity and protection means that such therapeutic modulation must strike a careful balance: manipulation of PNNs to promote plasticity may have unintended negative consequences resulting from excessive plasticity or from exposure of neurons to neurotoxins. [Trends Neurosci] Abstract

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Medicenna Presents Clinical Validation of the IL4 Receptor as a Biomarker for MDNA55 in Recurrent Glioblastoma

The presentation by Dr. Dina Randazzo of Duke University School of Medicine and a Principal Investigator in the Phase IIb clinical trial MDNA55-05, which recently completed its enrollment, focused on the development of a new biomarker test for the interleukin-4 (IL4) receptor that may enable better selection and superior treatment outcomes for patients with recurrent glioblastoma, a highly aggressive and uniformly fatal form of brain cancer. [Press release from Medicenna Therapeutics Corp. discussing research presented at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting, Chicago] Press Release

Adastra Pharmaceuticals Announces Positive Interim Data from Phase Ib Clinical Trial of Zotiraciclib in the Treatment of Recurrent Malignant Gliomas

Adastra Pharmaceuticals, Inc. announced interim data from a Phase Ib trial of the company’s lead clinical candidate, zotiraciclib, in combination with temozolomide for the treatment of recurrent malignant gliomas. [Press release from Adastra Pharmaceuticals, Inc. (PR Newswire Association LLC.) discussing research presented at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting, Chicago] Press Release

Ziopharm Oncology Provides Positive Clinical Data for Controlled IL-12 for the Treatment of Recurrent Glioblastoma

Ziopharm Oncology, Inc. announced the presentation of new interim analyses of clinical data from two ongoing substudies in its Controlled IL-12 platform, or Ad-RTS-hIL-12 plus veledimex, both as monotherapy and in combination with a PD-1 inhibitor, for the treatment of recurrent or progressive glioblastoma multiforme in adults. [Press release from Ziopharm Oncology, Inc. discussing research presented at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting, Chicago] Press Release

Radiographic Analysis of VB-111 Phase II and III Clinical Trials in Recurrent Glioblastoma Shows Survival Benefit Associated with Objective Responses and Distinct Signature of VB-111 Activity

VBL Therapeutics announced that MRI data from VB-111 Phase II and Phase III studies in recurrent GBM, presented, showed a survival benefit associated with objective responses to the compound and a distinct signature of VB-111 activity. [Press release from VBL Therapeutics discussing research presented at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting, Chicago] Press Release

Basilea Reports Publication of Clinical Data for Anticancer Drug Candidates BAL101553 in Glioblastoma and Derazantinib in Intrahepatic Cholangiocarcinoma

Basilea Pharmaceutica Ltd. reported the Phase I data from an ongoing study with the oral formulation of its novel tumor checkpoint controller, BAL101553, in brain cancer patients with progressive or recurrent glioblastoma, or high-grade glioma. The data were presented on June 2^nd, 2019. [Press release from Basilea Pharmaceutica Ltd. discussing research presented at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting, Chicago] Press Release

New Data on Larotrectinib Efficacy in Patients with TRK Fusion Cancer and Primary CNS Tumors or Brain Metastases Presented

A new analysis from clinical trials in patients with TRK fusion cancer and brain metastases or primary tumors of the central nervous system (CNS) confirm the strong activity of larotrectinib in both adults and children. In TRK fusion cancer patients with intracranial disease, the compound achieved responses and durable disease control, across age or tumor histology. [Press release from Bayer AG discussing research presented at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting, Chicago] Press Release

DelMar Provides Clinical Update on VAL-083 from Ongoing First- and Second-Line Trials in Patients with MGMT-Unmethylated Glioblastoma at a Key Opinion Leader Forum

DelMar Pharmaceuticals, Inc. presented clinical updates from the company’s ongoing first- and second-line trials in patients with MGMT-unmethylated glioblastoma multiforme (GBM) at a key opinion leader forum focused on brain tumors and the role of VAL-083 to address the unmet medical need in GBM. [Press release from DelMar Pharmaceuticals, Inc. discussing research presented at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting, Chicago] Press Release

Dr. Madeline Lancaster talks about her groundbreaking work generating ‘mini-brains’. Watch Now

Origenis GmbH Announces Research Collaboration with US Cancer Center

Origenis GmbH announced that the company has entered into a collaboration with Memorial Sloan Kettering Cancer Center, New York, targeting glioblastoma, a rare but fatal brain cancer. Under the research and collaboration agreement, Origenis will use its proprietary AI platform for drug discovery and development. [Origenis GmbH] Press Release

Vect-Horus Announces Collaboration and Option Agreement with Astellas Pharma

Vect-Horus announced the signing of the Research Collaboration and Option Agreement with Astellas Pharma Inc. Vect-Horus will use its proprietary technology VECTrans^® to transport Astellas’ antibody to the brain for the treatment of CNS diseases. [Vect-Horus] Press Release

BrainStorm Announces Second Clinical Site to Enroll Patients in Its Progressive MS Phase II Study

BrainStorm Cell Therapeutics Inc. announced that the Stanford University School of Medicine will serve as the second contracted clinical study site for the company’s Phase II open-label, multicenter study of repeated intrathecal administration of autologous MSC-NTF cells in participants with progressive Multiple Sclerosis (MS). [BrainStorm Cell Therapeutics Inc.] Press Release

AxoSim Licenses Revolutionary Mini-Brain Technology from Johns Hopkins University Enabling the Use of Human Data to Speed New Drug Research

AxoSim, Inc. announced an exclusive license from Johns Hopkins University to intellectual property underlying the “Mini-Brain” technology, which uses induced pluripotent stem cells to create functional models of the human brain. [AxoSim, Inc. (PR Newswire Association LLC.)] Press Release

Oligomerix, Inc Receives Ongoing Support for Tau Oligomer Inhibitor Program from National Institutes of Health

Oligomerix, Inc. announced the company has successfully completed Phase I of the work required under its Small Business Innovation Research Phase I/Phase II Fast-Track grant announced in October of 2018. The company recently received $1 million from the National Institutes of Health, National Institute on Aging to fund Phase II activities. [Oligomerix, Inc. (Business Wire, Inc.)] Press Release

Alzheimer’s Drug Discovery Foundation Announces the First Award Recipients of Its Diagnostics Accelerator Program

The Alzheimer’s Drug Discovery Foundation announced the first group of researchers who will receive funding through its Diagnostics Accelerator, a new research program that aims to fast-track the development of diagnostic tools and biomarkers for Alzheimer’s disease and related dementias. [The Alzheimer’s Drug Discovery Foundation] Press Release

NIH Has Referred 16 Allegations of Foreign Influence on US Research to Investigators

The National Institutes of Health (NIH) has referred 16 allegations related to foreign influence of US-funded research to investigators and contacted 61 research institutions about such concerns, federal health officials said at a hearing. [STAT News] Editorial

Hungarians Protest against Proposed Government Takeover of Science

Thousands of scientists and their supporters marched through the streets of Budapest on 2 June to protest against a proposed law that would give the Hungarian government direct control of the country’s top research institutes. [Nature News] Editorial

NEW Cell Symposia: Neuro-Immune Axis: Reciprocal Regulation in Development, Health, and Disease
September 22-24, 2019
Long Beach, California, United States

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NEW Postdoctoral Research Fellow – Molecular Neuroscience (Fred Hutchinson Cancer Research Center)

NEW Postdoctoral Fellow – Nanoparticle-Based Therapeutic Delivery to the Brain (Johns Hopkins School of Medicine)

NEW Postdoctoral Researcher – Brain Cancer Research (University of Alabama at Birmingham)

Postdoctoral Position – Neuropsychiatric Disorders (Stanford University)

Postdoctoral Fellow – Epigenetic Regulation of Neuronal Identity (The Helmholtz Pioneer Campus)

Associate Professor – Translational Psychiatry (Aarhus University)

Postdoctoral Positions – Neuroscience (Weill Cornell Medical College)

Postdoctoral Fellow – Ion Channel & Neuroscience Research (Johns Hopkins University)

Postdoctoral Fellow/Research Assistant Positions – Glioma Research (NIH National Cancer Institute Laboratory of Pathology)

Postdoctoral Position – Retinal Stem Cell Biology (Johns Hopkins University)

Postdoctoral Research Associate – Neurological Diseases (University of Utah)

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