Title:
POLYNUCLEOTIDE FOR TREATMENT OF NEURODEGENERATIVE DISEASE, VECTOR, CELL, PHARMACEUTICAL COMPOSITION, AND SCREENING METHOD
Document Type and Number:
WIPO Patent Application WO/2022/186089
Kind Code:
A1
Abstract:
The purpose of the present invention is to provide a novel method for increasing the number of newly generated neurons in the adult brain, and to provide a polynucleotide, a vector, and a pharmaceutical composition for use in the method. The present invention provides: a polynucleotide characterized by including (A) the nucleic acid sequence of the Plagl2 gene, (B) an miR-shRNA (microRNA adapted short hairpin RNA) nucleic acid sequence for the Dyrk1a gene, and (C) a promoter sequence operatively connected to the nucleic acid sequences; a vector including the polynucleotide; and a pharmaceutical composition including the polynucleotide and the vector.
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Inventors:
KAGEYAMA RYOICHIRO (JP)
KAISE TAKASHI (JP)
FUKUI MASAHIRO (JP)
KAISE TAKASHI (JP)
FUKUI MASAHIRO (JP)
Application Number:
PCT/JP2022/008055
Publication Date:
September 09, 2022
Filing Date:
February 25, 2022
Export Citation:
Assignee:
UNIV KYOTO (JP)
International Classes:
C12N15/12; A61K9/08; A61K31/7105; A61K31/713; A61K35/76; A61K35/761; A61K48/00; A61P25/00; A61P27/16; A61P43/00; C12N5/10; C12N15/11; C12N15/113; C12N15/86; C12Q1/06
Other References:
LECHNER CHRISTIAN, FLASSHOFF MAREN, FALKE HANNES, PREU LUTZ, LOAËC NADÉGE, MEIJER LAURENT, KNAPP STEFAN, CHAIKUAD APIRAT, KUNICK C: "[b]-Annulated Halogen-Substituted Indoles as Potential DYRK1A Inhibitors", MOLECULES, vol. 24, no. 22, pages 4090, XP055962765, DOI: 10.3390/molecules24224090
ZHENG HONGWU, YING HAOQIANG, WIEDEMEYER RUPRECHT, YAN HAIYAN, QUAYLE STEVEN N., IVANOVA ELENA V., PAIK JI-HYE, ZHANG HAILEI, XIAO : "PLAGL2 Regulates Wnt Signaling to Impede Differentiation in Neural Stem Cells and Gliomas", CANCER CELL, CELL PRESS, US, vol. 17, no. 5, 1 May 2010 (2010-05-01), US , pages 497 - 509, XP055962789, ISSN: 1535-6108, DOI: 10.1016/j.ccr.2010.03.020
GONçALVES J. TIAGO; SCHAFER SIMON T.; GAGE FRED H.: "Adult Neurogenesis in the Hippocampus: From Stem Cells to Behavior", CELL, ELSEVIER, AMSTERDAM NL, vol. 167, no. 4, 3 November 2016 (2016-11-03), Amsterdam NL , pages 897 - 914, XP029802728, ISSN: 0092-8674, DOI: 10.1016/j.cell.2016.10.021
KAISE TAKASHI, FUKUI MASAHIRO, SUEDA RISA, PIAO WENHUI, YAMADA MAYUMI, KOBAYASHI TAEKO, IMAYOSHI ITARU, KAGEYAMA RYOICHIRO: "Functional rejuvenation of aged neural stem cells by Plagl2 and anti-Dyrk1a activity", GENES & DEVELOPMENT, COLD SPRING HARBOR LABORATORY PRESS, PLAINVIEW, NY., US, vol. 36, no. 1-2, 1 January 2022 (2022-01-01), US , pages 23 - 37, XP055962795, ISSN: 0890-9369, DOI: 10.1101/gad.349000.121
NAGAHARA AH ET AL.: "Neuroprotective effects of brain-derived neurotrophic factor in rodent and primate models of Alzheimer's disease", NAT. MED., vol. 15, no. 3, 2009, pages 331 - 337
HENRIETTE VAN PRAAG ET AL.: "Exercise enhances learning and hippocampal neurogenesis in aged mice", J NEUROSCI., vol. 25, no. 38, 21 September 2005 (2005-09-21), pages 8680 - 5
BENEDETTA ARTEGIANI ET AL.: "Overexpression of cdk4 and cyclinDl triggers greater expansion of neural stem cells in the adult mouse brain", J EXP MED., vol. 208, no. 5, 9 May 2011 (2011-05-09), pages 937 - 48, XP055322769, DOI: 10.1084/jem.20102167
BENRAISS, A. ET AL.: "Mobilization of endogenous progenitor cells regenerates functionally-integrated medium spiny striopallidal projection neurons and delays disease progression in a transgenic model of Huntington's disease", CELL STEM CELL, vol. 12, 2013, pages 787 - 799
BERDUGO-VEGA, G. ET AL.: "Increasing neurogenesis refines hippocampal activity rejuvenating navigational learning strategies and contextual memory throughout life", NAT. COMMUN., vol. 11, 2020, pages 135
IMAYOSHI, I. ET AL.: "Roles of continuous neurogenesis in the structural and functional integrity of the adult forebrain", NAT NEUROSCI, vol. 11, 2008, pages 1153 - 1161
SHOJI, H.MIYAKAWA, T.: "Age-related behavioral changes from young to old age in male mice of a C57BL/6J strain maintained under a genetic stability program", NEUROPSYCHOPHARMACOL. REP., vol. 39, 2019, pages 100 - 118
WALGRAVE, H. ET AL., CELL STEM CELL, vol. 28, 2021, pages 1805 - 1821,e1808
ZHENG HONGWU, YING HAOQIANG, WIEDEMEYER RUPRECHT, YAN HAIYAN, QUAYLE STEVEN N., IVANOVA ELENA V., PAIK JI-HYE, ZHANG HAILEI, XIAO : "PLAGL2 Regulates Wnt Signaling to Impede Differentiation in Neural Stem Cells and Gliomas", CANCER CELL, CELL PRESS, US, vol. 17, no. 5, 1 May 2010 (2010-05-01), US , pages 497 - 509, XP055962789, ISSN: 1535-6108, DOI: 10.1016/j.ccr.2010.03.020
GONçALVES J. TIAGO; SCHAFER SIMON T.; GAGE FRED H.: "Adult Neurogenesis in the Hippocampus: From Stem Cells to Behavior", CELL, ELSEVIER, AMSTERDAM NL, vol. 167, no. 4, 3 November 2016 (2016-11-03), Amsterdam NL , pages 897 - 914, XP029802728, ISSN: 0092-8674, DOI: 10.1016/j.cell.2016.10.021
KAISE TAKASHI, FUKUI MASAHIRO, SUEDA RISA, PIAO WENHUI, YAMADA MAYUMI, KOBAYASHI TAEKO, IMAYOSHI ITARU, KAGEYAMA RYOICHIRO: "Functional rejuvenation of aged neural stem cells by Plagl2 and anti-Dyrk1a activity", GENES & DEVELOPMENT, COLD SPRING HARBOR LABORATORY PRESS, PLAINVIEW, NY., US, vol. 36, no. 1-2, 1 January 2022 (2022-01-01), US , pages 23 - 37, XP055962795, ISSN: 0890-9369, DOI: 10.1101/gad.349000.121
NAGAHARA AH ET AL.: "Neuroprotective effects of brain-derived neurotrophic factor in rodent and primate models of Alzheimer's disease", NAT. MED., vol. 15, no. 3, 2009, pages 331 - 337
HENRIETTE VAN PRAAG ET AL.: "Exercise enhances learning and hippocampal neurogenesis in aged mice", J NEUROSCI., vol. 25, no. 38, 21 September 2005 (2005-09-21), pages 8680 - 5
BENEDETTA ARTEGIANI ET AL.: "Overexpression of cdk4 and cyclinDl triggers greater expansion of neural stem cells in the adult mouse brain", J EXP MED., vol. 208, no. 5, 9 May 2011 (2011-05-09), pages 937 - 48, XP055322769, DOI: 10.1084/jem.20102167
BENRAISS, A. ET AL.: "Mobilization of endogenous progenitor cells regenerates functionally-integrated medium spiny striopallidal projection neurons and delays disease progression in a transgenic model of Huntington's disease", CELL STEM CELL, vol. 12, 2013, pages 787 - 799
BERDUGO-VEGA, G. ET AL.: "Increasing neurogenesis refines hippocampal activity rejuvenating navigational learning strategies and contextual memory throughout life", NAT. COMMUN., vol. 11, 2020, pages 135
IMAYOSHI, I. ET AL.: "Roles of continuous neurogenesis in the structural and functional integrity of the adult forebrain", NAT NEUROSCI, vol. 11, 2008, pages 1153 - 1161
SHOJI, H.MIYAKAWA, T.: "Age-related behavioral changes from young to old age in male mice of a C57BL/6J strain maintained under a genetic stability program", NEUROPSYCHOPHARMACOL. REP., vol. 39, 2019, pages 100 - 118
WALGRAVE, H. ET AL., CELL STEM CELL, vol. 28, 2021, pages 1805 - 1821,e1808
Attorney, Agent or Firm:
TSUKUNI & ASSOCIATES (JP)
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