Neural Cell News Volume 13.19 | May 22 2019

TOP STORY

Progenitors from the Central Nervous System Drive Neurogenesis in Cancer

Researchers showed that neural progenitors from the central nervous system that express doublecortin (DCX⁺) infiltrate prostate tumors and metastases, in which they initiate neurogenesis. In mouse models of prostate cancer, oscillations of DCX⁺ neural progenitors in the subventricular zone were associated with disruption of the blood-brain barrier, and with the egress of DCX⁺ cells into the circulation. [Nature] Abstract | Press Release

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Single-Cell Genomics Identifies Cell Type-Specific Molecular Changes in Autism

Scientists used single-nucleus RNA sequencing of cortical tissue from patients with autism to identify autism-associated transcriptomic changes in specific cell types. They found that synaptic signaling of upper-layer excitatory neurons and the molecular state of microglia were preferentially affected in autism. [Science] Full Article | Press Release

Elevating Growth Factor Responsiveness and Axon Regeneration by Modulating Presynaptic Inputs

The authors overexpressed Lin28 in the retina. Lin28-treated retinas responded to insulin-like growth factor-1 by initiating retinal ganglion cell (RGC) axon regeneration after axotomy. This effect was cell non-autonomous. Lin28 expression was required only in amacrine cells, inhibitory neurons that innervate RGCs. [Neuron] Abstract

Membralin Deficiency Dysregulates Astrocytic Glutamate Homeostasis Leading to ALS-Like Impairment

Reduced membralin and EAAT2 levels correlated with disease progression in spinal cord from SOD1-mutant mouse models, and reductions in membralin/EAAT2 were observed in human ALS spinal cord. Overexpression of membralin in SOD1^G93A astrocytes decreased TNFR1 levels and increased EAAT2 expression, and improved motor neuron survival. [J Clin Invest] Abstract | Full Article | Graphical Abstract

Yin Yang 1 Sustains Biosynthetic Demands during Brain Development in a Stage-Specific Manner

Researchers showed that Yin Yang 1 (YY1) controlled murine cerebral cortex development in a stage-dependent manner. By regulating a wide range of metabolic pathways and protein translation, Yy1 maintained proliferation and survival of neural progenitor cells at early stages of brain development. [Nat Commun] Full Article

The Long Noncoding RNA Pnky Is a trans-Acting Regulator of Cortical Development In Vivo

The authors showed that conditional deletion of Pnky from the developing cortex regulated the production of projection neurons from neural stem cells in a cell-autonomous manner, altering postnatal cortical lamination. Surprisingly, Pou3f2 expression was not disrupted by deletion of the entire Pnky gene. [Dev Cell] Abstract | Graphical Abstract

Cellular Labeling of Endogenous Retrovirus Replication (CLEVR) Reveals De Novo Insertions of the Gypsy Retrotransposable Element in Cell Culture and in Both Neurons and Glial Cells of Aging Fruit Flies

The gypsy-CLEVR reporter revealed gypsy replication both in cell culture and in individual neurons and glial cells of the aging adult fly. Scientists also demonstrated that the gypsy-CLEVR replication rate was increased when the short interfering RNA silencing system was genetically disrupted. [PLoS Biol] Full Article

ZEB1 Represses Neural Differentiation and Cooperates with CTBP2 to Dynamically Regulate Cell Migration during Neocortex Development

Overexpression of zinc-finger E-box binding homeobox 1 (Zeb1) during neuronal differentiation, when its expression normally declines, blocked neural progenitor cell lineage progression and disrupted multipolar-to-bipolar transition of differentiating neurons, leading to severe migration defects and subcortical heterotopia bands at postnatal stages. [Cell Rep] Full Article | Graphical Abstract

Sonic Hedgehog Effectively Improves Oct4-Mediated Reprogramming of Astrocytes into Neural Stem Cells

Oct4-driven reprogramming of astrocytes into induced neural stem cells (iNSCs) was potentiated with continuous sonic hedgehog stimulation, as demonstrated by sped-up reprogramming and increased conversion efficiency. Moreover, the iNSCs-derived neurons possessed functionality as neurons. [Mol Ther] Abstract | Graphical Abstract

The Kinase Inhibitor SI113 Induces Autophagy and Synergizes with Quinacrine in Hindering the Growth of Human Glioblastoma Multiforme Cells

SI113 strongly affected the PI3K/mTOR pathway, evoking a pro-survival autophagic response in neurospheres. These results suggested the use of SI113 coupled, for maximum efficiency, with autophagy inhibitors. Indeed, the association of SI113 with an autophagy inhibitor, the antimalarial drug quinacrine, induced a strong synergistic effect in inhibiting glioblastoma multiforme growth properties in all the cells tested, including neurospheres. [J Exp Clin Cancer Res] Full Article

MeHg-Induced Autophagy via JNK/Vps34 Complex Pathway Promotes Autophagosome Accumulation and Neuronal Cell Death

Investigators demonstrated that methylmercury (MeHg) induced mTOR-independent autophagy through JNK/Vps34 complex pathway, which further promoted autophagosome accumulation and neuronal cell death. In addition to cell death, MeHg increased LC3-II expression in a concentration- and time-dependent manner in neuronal cells; furthermore, western blot analysis of LC3-II expression under baf A1-treated condition indicated that MeHg activated autophagy induction. [Cell Death Dis] Full Article

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Astrocytes: Emerging Therapeutic Targets in Neurological Disorders

Although rectifying astrocyte malfunction has successfully counteracted disease pathogenesis and outcome in many preclinical settings, the translation of this revolutionary approach into clinical practice urges the development of innovative, safe, and effective systems for both the selective delivery of therapeutics to the astrocytes and astrocyte replacement strategies. [Trends Mol Med] Abstract

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Brain Balance Achievement Centers Announces Collaboration with Renowned Neuroscientist

Brain Balance Achievement Centers announced a nationwide collaboration with Cambridge Brain Sciences (CBS). Brain Balance is collaborating with CBS on a variety of efforts, including providing access to data in an effort to study changes in cognitive development over time and how developmental concerns impacts cognition in children and young adults. [Brain Balance Achievement Centers] Press Release

Corrona Expands Its Real-World Evidence Registry Collaboration for Patients with Multiple Sclerosis

Corrona, LLC announced a key milestone for the Corrona^® Multiple Sclerosis (MS) Registry, a real-world US-based registry developed as a collaborative effort with the National MS Society. The collaborative registry model now includes Genentech as the first pharmaceutical company to support and participate in the registry. [Corrona, LLC] Press Release

Kazia Enters Clinical Collaboration for Metastatic Brain Cancer with Alliance for Clinical Trials in Oncology

Kazia Therapeutics Limited announced that it has entered into a collaboration with the Alliance for Clinical Trials in Oncology Foundation. Alliance will launch a multi-centre Phase II study to investigate the potential use of Kazia’s investigational new drug, GDC-0084, alongside several other targeted cancer therapies, in the treatment of brain metastases. [Kazia Therapeutics Limited] Press Release

AbbVie Provides Update on Depatuxizumab Mafodotin (Depatux-M), an Investigational Medicine for Newly Diagnosed Glioblastoma, an Aggressive Form of Brain Cancer

AbbVie announced the Phase III INTELLANCE-1 study of depatuxizumab mafodotin in patients with newly diagnosed glioblastoma, whose tumors have epidermal growth factor receptor amplification, demonstrated no survival benefit for patients receiving Depatux-M at an interim analysis. [AbbVie Inc.] Press Release

Tocagen’s Toca 5 Pivotal Phase III Clinical Trial in Patients with Recurrent Brain Cancer Continues without Modification at Planned Interim Analysis

Tocagen Inc. announced the Toca 5 Phase III clinical trial evaluating Toca 511 & Toca FC in patients with recurrent high grade glioma continues without modification following a planned interim analysis of data conducted by an Independent Data Monitoring Committee. [Tocagen Inc.] Press Release

BioArctic Receives MEUR 15 Milestone Payment from Eisai for Start of BAN2401 Confirmatory Phase III Study in Early Alzheimer’s Disease

BioArctic AB announced that the company will receive a milestone payment of MEUR 15 from its partner Eisai for the achievement of the first patient being dosed in the global, single confirmatory Phase III study with BAN2401 in early Alzheimer´s disease. [BioArctic AB] Press Release

Mustang Bio and Nationwide Children’s Hospital Receive Orphan Drug Designation for MB-108 (Oncolytic Virus C134) for the Treatment of Malignant Glioma

Mustang Bio, Inc. and Nationwide Children’s Hospital announced that the FDA has granted Orphan Drug Designation to MB-108 for the treatment of malignant glioma, a type of brain cancer with a median survival of less than 18 months. Nationwide Children’s has exclusively licensed oncolytic virus C134 to Mustang. [Mustang Bio, Inc.] Press Release

UCB Announces NAYZILAM^® (Midazolam) Nasal Spray Now Approved by FDA to Treat Intermittent, Stereotypic Episodes of Frequent Seizure Activity in People Living with Epilepsy in the US

UCB announced that the FDA has approved a New Drug Application for the company’s newest anti-epileptic drug NAYZILAM^® nasal spray CIV, a benzodiazepine indicated for the acute treatment of intermittent, stereotypic episodes of frequent seizure activity that are distinct from a patient’s usual seizure pattern in patients with epilepsy 12 years of age and older. [UCB, Inc.] Press Release

Critical Windows When Experience Shapes the Brain

Pat Levitt, PhD, Chief Scientific Officer at Children’s Hospital Los Angeles and Simms/Mann Chair in Developmental Neurogenetics, received a $3.7M grant from the National Institute of Mental Health to study development of neural circuits. [Children’s Hospital Los Angeles] Press Release

Neuralstem Announces Issuance of New Patent Covering Broad Therapeutic Use of Neural Stem Cells

Neuralstem, Inc. announced the expansion of their intellectual property portfolio with the recent issuance of a newly published patent. US Patent No. 10,286,010, entitled “Methods of Treating Neurodegenerative Conditions” was issued, by the United States Patent and Trademark Office. The patent covers the use of transplanted human neural stem cells for the treatment of neurodegeneration resulting from disease and injury. [Neuralstem, Inc.] Press Release

uniQure Strengthens Intellectual Property Portfolio with Granted Patent Claims Covering AMT-130 for Huntington’s Disease

uniQure N.V. announced the issuance of two new patents covering AMT-130, the company’s gene therapy candidate for the treatment of Huntington’s disease. AMT-130 comprises a recombinant AAV5 vector carrying a DNA cassette, encoding a microRNA that non-selectively lowers or knocks-down human huntingtin protein in Huntington’s disease patients. [uniQure N.V.] Press Release

How European Scientists Will Spend €100 Billion

Politicians don’t win prizes for speed, but the European Union’s parliament and the leaders of its member states made record time this year when they hammered out an agreement that could supply researchers in Europe with more than €100 billion (US$113 billion) over seven years. [Nature News] Editorial

National Cancer Institute Will Stop Funding Nanotechnology Centers

The end to funding represents a “natural transition” from putting dedicated support into an emerging field to becoming a more mature research field that fits in with other cancer fields, says Piotr Grodzinski of the National Cancer Institute’s Nanodelivery Systems and Devices Branch, which oversees the Centers of Cancer Nanotechnology Excellence, to Science. [The Scientist] Editorial

NEW Cell Symposia: Engineering Organoids and Organs
August 25-27, 2019
San Diego, California, United States

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

NEW Associate Professor – Translational Psychiatry (Aarhus University)

Postdoctoral Positions – Neuroscience (Weill Cornell Medical College)

Lecturer – Neuroscience (University College London)

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

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

Postdoctoral Positions – Astrocyte Research (Washington University in St.Louis)

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

Postdoctoral Fellow – Alcohol & Adult Neurogenesis (The University of Texas at Austin)

Postdoctoral Research Associate – Neurological Diseases (University of Utah)

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