WO2023183371A8 - Engineered heart tissue model of restrictive cardiomyopathy for drug discovery - Google Patents

Engineered heart tissue model of restrictive cardiomyopathy for drug discovery Download PDF

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Publication number
WO2023183371A8
WO2023183371A8 PCT/US2023/015878 US2023015878W WO2023183371A8 WO 2023183371 A8 WO2023183371 A8 WO 2023183371A8 US 2023015878 W US2023015878 W US 2023015878W WO 2023183371 A8 WO2023183371 A8 WO 2023183371A8
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WIPO (PCT)
Prior art keywords
methods
cell
restrictive cardiomyopathy
drug discovery
heart tissue
Prior art date
Application number
PCT/US2023/015878
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French (fr)
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WO2023183371A3 (en
WO2023183371A2 (en
Inventor
Barry FINE
Xiaokan ZHANG
Bryan Wang
Trevor Ray NASH
Gordana Vunjak-Novakovic
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The Trustees Of Columbia University In The City Of New York
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Application filed by The Trustees Of Columbia University In The City Of New York filed Critical The Trustees Of Columbia University In The City Of New York
Publication of WO2023183371A2 publication Critical patent/WO2023183371A2/en
Publication of WO2023183371A3 publication Critical patent/WO2023183371A3/en
Publication of WO2023183371A8 publication Critical patent/WO2023183371A8/en

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    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
    • C12N5/06—Animal cells or tissues; Human cells or tissues
    • C12N5/0602—Vertebrate cells
    • C12N5/0652—Cells of skeletal and connective tissues; Mesenchyme
    • C12N5/0657—Cardiomyocytes; Heart cells
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
    • C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
    • C07K14/4701—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals not used
    • C07K14/4716—Muscle proteins, e.g. myosin, actin
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
    • G01N33/5008—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
    • G01N33/502—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics for testing non-proliferative effects
    • G01N33/5026—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics for testing non-proliferative effects on cell morphology
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
    • G01N33/5008—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
    • G01N33/5044—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics involving specific cell types
    • G01N33/5061—Muscle cells
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    • C12N2502/00—Coculture with; Conditioned medium produced by
    • C12N2502/13—Coculture with; Conditioned medium produced by connective tissue cells; generic mesenchyme cells, e.g. so-called "embryonic fibroblasts"
    • C12N2502/1323—Adult fibroblasts
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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    • C12N2502/00—Coculture with; Conditioned medium produced by
    • C12N2502/13—Coculture with; Conditioned medium produced by connective tissue cells; generic mesenchyme cells, e.g. so-called "embryonic fibroblasts"
    • C12N2502/1329—Cardiomyocytes
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    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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    • C12N2502/00—Coculture with; Conditioned medium produced by
    • C12N2502/45—Artificially induced pluripotent stem cells
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    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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    • C12N2502/00—Coculture with; Conditioned medium produced by
    • C12N2502/99—Coculture with; Conditioned medium produced by genetically modified cells
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    • C12N2503/00—Use of cells in diagnostics
    • C12N2503/04—Screening or testing on artificial tissues
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    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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    • C12N2513/00—3D culture

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Chemical & Material Sciences (AREA)
  • Cell Biology (AREA)
  • Immunology (AREA)
  • Molecular Biology (AREA)
  • General Health & Medical Sciences (AREA)
  • Hematology (AREA)
  • Biotechnology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Urology & Nephrology (AREA)
  • Organic Chemistry (AREA)
  • Biochemistry (AREA)
  • Genetics & Genomics (AREA)
  • Medicinal Chemistry (AREA)
  • Zoology (AREA)
  • Toxicology (AREA)
  • Microbiology (AREA)
  • General Physics & Mathematics (AREA)
  • Physics & Mathematics (AREA)
  • Wood Science & Technology (AREA)
  • Pathology (AREA)
  • Analytical Chemistry (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Food Science & Technology (AREA)
  • Cardiology (AREA)
  • Rheumatology (AREA)
  • Biophysics (AREA)
  • Gastroenterology & Hepatology (AREA)
  • General Engineering & Computer Science (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Physiology (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)

Abstract

Described herein is a novel mutation in Filamin C (FLNC) in a patient with early onset restrictive cardiomyopathy and utilization of induced pluripotent stem cell derived cardiomyocytes (iPSC-CM) derived from this patient to generate a cell-based model of impaired cardiomyocyte relaxation. In certain aspects, the provided herein are methods of identifying a compound that modulates relaxation velocity of a contractile cell or a beating cardiomyocyte, methods of observing a dynamic physical property of a beating cardiomyocyte, methods of identifying compounds that modulate a dynamic physical property of an engineered cardiac tissue, methods of treating a cardiomyopathy, cell lines, and engineered cardiac tissue.
PCT/US2023/015878 2022-03-22 2023-03-22 Engineered heart tissue model of restrictive cardiomyopathy for drug discovery WO2023183371A2 (en)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US202263322599P 2022-03-22 2022-03-22
US63/322,599 2022-03-22
US202263327639P 2022-04-05 2022-04-05
US63/327,639 2022-04-05

Publications (3)

Publication Number Publication Date
WO2023183371A2 WO2023183371A2 (en) 2023-09-28
WO2023183371A3 WO2023183371A3 (en) 2023-10-26
WO2023183371A8 true WO2023183371A8 (en) 2023-11-30

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PCT/US2023/015878 WO2023183371A2 (en) 2022-03-22 2023-03-22 Engineered heart tissue model of restrictive cardiomyopathy for drug discovery

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WO (1) WO2023183371A2 (en)

Family Cites Families (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9404140B1 (en) * 2009-11-03 2016-08-02 The University Of Central Florida Research Foundation, Inc. Patterned cardiomyocyte culture on microelectrode array
WO2015156929A1 (en) * 2014-04-07 2015-10-15 The Trustees Of Columbia University In The City Of New York Method for culture of human bladder cell lines and organoids and uses thereof
US10613078B2 (en) * 2015-02-20 2020-04-07 Ncardia B.V. Assays for measuring cardiotoxicity
US20210001339A1 (en) * 2017-01-05 2021-01-07 Microsensor Labs, LLC System and method for detection and sorting of cells
JP6940920B2 (en) * 2017-02-04 2021-09-29 アナバイオス コーポレーション Systems and methods for predicting drug-induced inotropic effects and risk of arrhythmia induction
WO2019035032A2 (en) * 2017-08-16 2019-02-21 University Of Washington Compositions and methods for enhancing maturation states of healthy and diseased cardiomyocytes
EP3765486A4 (en) * 2018-03-16 2022-03-02 The Board of Trustees of the Leland Stanford Junior University Reagents and methods with wnt agonists and bioactive lipids for generating and expanding cardiomyocytes
JP2022520148A (en) * 2018-12-06 2022-03-29 アークトゥラス・セラピューティクス・インコーポレイテッド Modified proteins and related treatment methods
JP2022538231A (en) * 2019-06-25 2022-09-01 モレキュラー デバイシーズ， エルエルシー Analysis of oscillatory fluorescence from biological cells

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WO2023183371A3 (en) 2023-10-26
WO2023183371A2 (en) 2023-09-28

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