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WO2009146033A3 - Compositions and methods for modulating smn activity - Google Patents

Compositions and methods for modulating smn activity Download PDF

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Publication number
WO2009146033A3
WO2009146033A3 PCT/US2009/038973 US2009038973W WO2009146033A3 WO 2009146033 A3 WO2009146033 A3 WO 2009146033A3 US 2009038973 W US2009038973 W US 2009038973W WO 2009146033 A3 WO2009146033 A3 WO 2009146033A3
Authority
WO
WIPO (PCT)
Prior art keywords
methods
compositions
sma
present
smn
Prior art date
Application number
PCT/US2009/038973
Other languages
French (fr)
Other versions
WO2009146033A2 (en
Inventor
Howard Chia-Chang Chang
Douglas N. Dimlich
Takakazu Yokokura
Mark W. Kankel
Anindya Sen
Ashim Mukherjee
Vasanthi Sridhar
Tudor A. Fulga
Anne C. Hart
David Van Vactor
Spyros Artavanis-Tsakonas
Original Assignee
Sma Foundation
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Sma Foundation filed Critical Sma Foundation
Publication of WO2009146033A2 publication Critical patent/WO2009146033A2/en
Publication of WO2009146033A3 publication Critical patent/WO2009146033A3/en

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7088—Compounds having three or more nucleosides or nucleotides
    • A61K31/7105—Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K67/00—Rearing or breeding animals, not otherwise provided for; New or modified breeds of animals
    • A01K67/60—New or modified breeds of invertebrates
    • A01K67/61—Genetically modified invertebrates, e.g. transgenic or polyploid
    • A01K67/65—Genetically modified arthropods
    • A01K67/68—Genetically modified insects
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular system
    • 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
    • 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
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K2217/00—Genetically modified animals
    • A01K2217/05—Animals comprising random inserted nucleic acids (transgenic)
    • A01K2217/054—Animals comprising random inserted nucleic acids (transgenic) inducing loss of function
    • A01K2217/058—Animals comprising random inserted nucleic acids (transgenic) inducing loss of function due to expression of inhibitory nucleic acid, e.g. siRNA, antisense
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K2227/00—Animals characterised by species
    • A01K2227/70—Invertebrates
    • A01K2227/706—Insects, e.g. Drosophila melanogaster, medfly
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K2267/00—Animals characterised by purpose
    • A01K2267/03—Animal model, e.g. for test or diseases
    • A01K2267/0306—Animal model for genetic diseases
    • A01K2267/0318—Animal model for neurodegenerative disease, e.g. non- Alzheimer's
    • 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
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/10—Type of nucleic acid
    • C12N2310/14—Type of nucleic acid interfering nucleic acids [NA]

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Molecular Biology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Zoology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Biomedical Technology (AREA)
  • Biochemistry (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Biophysics (AREA)
  • Environmental Sciences (AREA)
  • General Chemical & Material Sciences (AREA)
  • Biotechnology (AREA)
  • General Engineering & Computer Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Wood Science & Technology (AREA)
  • Physics & Mathematics (AREA)
  • Toxicology (AREA)
  • Neurology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Epidemiology (AREA)
  • Plant Pathology (AREA)
  • Microbiology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Animal Husbandry (AREA)
  • Biodiversity & Conservation Biology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

The present invention provides novel genetic modifiers of SMN function. In particular, the present invention provides methods of treating spinal muscular atrophy (SMA) in a subject in need thereof by manipulating specific genes in the BMP and FGF signaling cascades as well as genes related to control of translation and the cytoskeleton. Hypomorphic Smn Drosophila strains, which more closely mimic (SMA) pathology, and methods of using such strains for screening putative therapeutic compounds are also disclosed.
PCT/US2009/038973 2008-03-31 2009-03-31 Compositions and methods for modulating smn activity WO2009146033A2 (en)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US4096408P 2008-03-31 2008-03-31
US61/040,964 2008-03-31
US9393108P 2008-09-03 2008-09-03
US61/093,931 2008-09-03

Publications (2)

Publication Number Publication Date
WO2009146033A2 WO2009146033A2 (en) 2009-12-03
WO2009146033A3 true WO2009146033A3 (en) 2010-01-21

Family

ID=41377850

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2009/038973 WO2009146033A2 (en) 2008-03-31 2009-03-31 Compositions and methods for modulating smn activity

Country Status (1)

Country Link
WO (1) WO2009146033A2 (en)

Families Citing this family (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP3377073A4 (en) 2015-11-16 2019-06-26 Ohio State Innovation Foundation METHODS AND COMPOSITIONS FOR TREATING DISORDERS AND DISEASES USING MOTONURON SURVIVAL PROTEIN (SMN)
EP3500675A4 (en) 2016-08-19 2020-01-29 Whitehead Institute for Biomedical Research METHODS FOR EDITING DNA METHYLATION
WO2018049077A1 (en) 2016-09-07 2018-03-15 Flagship Pioneering, Inc. Methods and compositions for modulating gene expression
US20200149039A1 (en) 2016-12-12 2020-05-14 Whitehead Institute For Biomedical Research Regulation of transcription through ctcf loop anchors
ES2949801T3 (en) 2017-01-09 2023-10-03 Whitehead Inst Biomedical Res Methods to alter gene expression by perturbation of transcription factor multimers that structure regulatory loops
CN108707628B (en) * 2018-05-28 2021-11-23 上海海洋大学 Preparation method of zebra fish notch2 gene mutant
MX2023002106A (en) 2020-08-21 2023-03-15 Genzyme Corp Fgfr3 antibodies and methods of use.

Non-Patent Citations (5)

* Cited by examiner, † Cited by third party
Title
CHAN, Y. B. ET AL.: "Neuromuscular Defects in a Drosophila Survival Motor Neuron Gene Mutant.", HUM. MOL. GENET., vol. 12, no. 12, June 2003 (2003-06-01), pages 1367 - 1376 *
EL-KHODOR, B. F. ET AL.: "Identification of a Battery of Tests for Drug Candidate Evaluation in the SMNDELTA7 Neonate Model of Spinal Muscular Atrophy.", EXP. NEUROL., vol. 212, no. 1, 18 March 2008 (2008-03-18), pages 29 - 43 *
JARECKI, J. ET AL.: "Diverse Small-Molecule Modulators of SMN Expression Found by High- Throughput Compound Screening: Early Leads towards a therapeutic for Spinal Muscular Atrophy.", HUM. MOL. GENET., vol. 14, no. 14, July 2005 (2005-07-01), pages 2003 - 2018 *
PERIMON, N. ET AL.: "Drug-Target Identification in Drosophila Cells: Combining High-Throughut RNAi and Small-Molecule Screens.", DRUG DISCOV TODAY, vol. 12, no. 1-2, January 2007 (2007-01-01), pages 28 - 33 *
RAJENDRA, T. K. ET AL.: "A Drosophila melanogaster Model of Spinal Muscular Atrophy Reveals a Function for SMN in Striated Muscle", J. CELL BIOL., vol. 176, no. 6, March 2007 (2007-03-01), pages 831 - 841 *

Also Published As

Publication number Publication date
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