Title:
APPLICATION OF PTBP1 INHIBITOR IN PREVENTING AND/OR TREATING NERVOUS SYSTEM DISEASE RELATED TO FUNCTIONAL NEURONAL DEATH
Document Type and Number:
WIPO Patent Application WO/2021/032068
Kind Code:
A1
Abstract:
An application of a Ptbp1 inhibitor in preventing and/or treating a nervous system disease related to functional neuronal death. Specifically, provided is a use of a Ptbp1 gene or RNA or an encoded protein inhibitor thereof in preparing a composition or a preparation. The composition or the preparation is used for preventing and/or treating a nervous system disease related to functional neuronal death. By inhibiting the expression or activity of the Ptbp1 gene or RNA or encoded protein thereof in astrocytes in the brain, the transdifferentiation of the astrocytes into dopamine neurons can be effectively induced. In addition, by inhibiting the expression or activity of the Ptbp1 gene or RNA or encoded protein thereof in muller glial cells in the retinal, the transdifferentiation of the muller glial cells into retinal ganglion cells can be effectively induced, thereby preventing and/or treating a nervous system disease related to functional neuronal death.
Inventors:
YANG HUI (CN)
ZHOU HAIBO (CN)
ZHOU HAIBO (CN)
Application Number:
PCT/CN2020/109653
Publication Date:
February 25, 2021
Filing Date:
August 17, 2020
Export Citation:
Assignee:
CENTER FOR EXCELLENCE IN BRAIN SCIENCE AND INTELLIGENCE TECH CHINESE ACADEMY OF SCIENCES (CN)
International Classes:
C12N5/079; A61K48/00; A61P25/00; C07K14/47; C12N15/864
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Other References:
ZHOU HAIBO, SU JINLIN, HU XINDE, ZHOU CHANGYANG, LI HE, CHEN ZHAORONG, XIAO QINGQUAN, WANG BO, WU WENYAN, SUN YIDI, ZHOU YINGSI, T: "Glia-to-Neuron Conversion by CRISPR-CasRx Alleviates Symptoms of Neurological Disease in Mice", CELL, vol. 181, no. 3, 1 April 2020 (2020-04-01), Amsterdam NL, pages 590 - 603, XP055782153, ISSN: 0092-8674, DOI: 10.1016/j.cell.2020.03.024
YUANCHAO XUE, KUNFU OUYANG, JIE HUANG, YU ZHOU, HONG OUYANG, HAIRI LI, GANG WANG, QIJIA WU, CHAOLIANG WEI, YANZHEN BI, LI JIANG, Z: "Direct Conversion of Fibroblasts to Neurons by Reprogramming PTB-Regulated MicroRNA Circuits", CELL, vol. 152, no. 1-2, 1 January 2013 (2013-01-01), Amsterdam NL, pages 82 - 96, XP055344151, ISSN: 0092-8674, DOI: 10.1016/j.cell.2012.11.045
WOHL STEFANIE GABRIELE, REH THOMAS ANDREW: "miR-124-9-9* potentiates Ascl1-induced reprogramming of cultured Muller glia", GLIA, vol. 64, no. 5, 1 May 2016 (2016-05-01), US, pages 743 - 762, XP055782144, ISSN: 0894-1491, DOI: 10.1002/glia.22958
LINARES, ANTHONY J.; LIN, CHIA-HO; DAMIANOV, ANDREY; ADAMS, KATRINA L; NOVITCH, BENNETT G.; BLACK, DOUGLAS L.: "The splicing regulator PTBP1 controls the activity of the transcription factor Pbx1 during neuronal differentiation", ELIFE, vol. 4, e09268, 24 December 2015 (2015-12-24), pages 1 - 25, XP009526193, ISSN: 2050-084X, DOI: 10.7554/eLife.09268.001
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ZHOU, H. ET AL.: "Cerebellar modules operate at different frequencies", ELIFE, vol. 3, 2014, pages e02536
XU, H.T. ET AL.: "Distinct lineage-dependent structural and functional organization of the hippocampus", CELL, vol. 157, 2014, pages 1552 - 1564, XP028874988, DOI: 10.1016/j.cell.2014.03.067
SU, J. ET AL.: "Reduction of HIP2 expression causes motor function impairment and increased vulnerability to dopaminergic degeneration in Parkinson's disease models", CELL DEATH DIS, vol. 9, 2018, pages 1020
CHAVEZ, A. ET AL.: "Comparison of Cas9 activators in multiple species", NAT METHODS, vol. 13, 2016, pages 563 - 567, XP055389670, DOI: 10.1038/nmeth.3871
QIAN, HAO ET AL.: "Reversing a model of Parkinson's disease with in situ converted nigral neurons", NATURE, vol. 582, 2020, pages 550 - 556, XP037525854, DOI: 10.1038/s41586-020-2388-4
ZHOU, HAIBO: " Glia-to-Neuron Conversion by CRISPR-CasRx Alleviates Symptoms of Neurological Disease in Mice", CELL, vol. 181, 2020, pages 590 - 603
YUANCHAO XUE, KUNFU OUYANG, JIE HUANG, YU ZHOU, HONG OUYANG, HAIRI LI, GANG WANG, QIJIA WU, CHAOLIANG WEI, YANZHEN BI, LI JIANG, Z: "Direct Conversion of Fibroblasts to Neurons by Reprogramming PTB-Regulated MicroRNA Circuits", CELL, vol. 152, no. 1-2, 1 January 2013 (2013-01-01), Amsterdam NL, pages 82 - 96, XP055344151, ISSN: 0092-8674, DOI: 10.1016/j.cell.2012.11.045
WOHL STEFANIE GABRIELE, REH THOMAS ANDREW: "miR-124-9-9* potentiates Ascl1-induced reprogramming of cultured Muller glia", GLIA, vol. 64, no. 5, 1 May 2016 (2016-05-01), US, pages 743 - 762, XP055782144, ISSN: 0894-1491, DOI: 10.1002/glia.22958
LINARES, ANTHONY J.; LIN, CHIA-HO; DAMIANOV, ANDREY; ADAMS, KATRINA L; NOVITCH, BENNETT G.; BLACK, DOUGLAS L.: "The splicing regulator PTBP1 controls the activity of the transcription factor Pbx1 during neuronal differentiation", ELIFE, vol. 4, e09268, 24 December 2015 (2015-12-24), pages 1 - 25, XP009526193, ISSN: 2050-084X, DOI: 10.7554/eLife.09268.001
"GenBank", Database accession no. 19205
SAMBROOK: "molecular cloning: conditions described in laboratory manual", 1989, COLD SPRING HARBOR LABORATORY PRESS
MCCARTHY, K.D.DEVELLIS, J.: "Preparation Of Separate Astroglial And Oligodendroglial Cell-Cultures From Rat Cerebral Tissue", JOURNAL OF CELL BIOLOGY, vol. 85, 1980, pages 890 - 902
ZHOU, H. ET AL.: "Cerebellar modules operate at different frequencies", ELIFE, vol. 3, 2014, pages e02536
XU, H.T. ET AL.: "Distinct lineage-dependent structural and functional organization of the hippocampus", CELL, vol. 157, 2014, pages 1552 - 1564, XP028874988, DOI: 10.1016/j.cell.2014.03.067
SU, J. ET AL.: "Reduction of HIP2 expression causes motor function impairment and increased vulnerability to dopaminergic degeneration in Parkinson's disease models", CELL DEATH DIS, vol. 9, 2018, pages 1020
CHAVEZ, A. ET AL.: "Comparison of Cas9 activators in multiple species", NAT METHODS, vol. 13, 2016, pages 563 - 567, XP055389670, DOI: 10.1038/nmeth.3871
QIAN, HAO ET AL.: "Reversing a model of Parkinson's disease with in situ converted nigral neurons", NATURE, vol. 582, 2020, pages 550 - 556, XP037525854, DOI: 10.1038/s41586-020-2388-4
ZHOU, HAIBO: " Glia-to-Neuron Conversion by CRISPR-CasRx Alleviates Symptoms of Neurological Disease in Mice", CELL, vol. 181, 2020, pages 590 - 603
Attorney, Agent or Firm:
XU & PARTNERS, LLC. (CN)
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