WO2006091964A2 - Regulators of protein misfolding and aggregation and methods of using the same - Google Patents
Regulators of protein misfolding and aggregation and methods of using the same Download PDFInfo
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- WO2006091964A2 WO2006091964A2 PCT/US2006/007002 US2006007002W WO2006091964A2 WO 2006091964 A2 WO2006091964 A2 WO 2006091964A2 US 2006007002 W US2006007002 W US 2006007002W WO 2006091964 A2 WO2006091964 A2 WO 2006091964A2
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- proteins
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Classifications
-
- 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
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/14—Hydrolases (3)
- C12N9/48—Hydrolases (3) acting on peptide bonds (3.4)
- C12N9/50—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25)
- C12N9/64—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue
-
- 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
- G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
- G01N33/6893—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids related to diseases not provided for elsewhere
- G01N33/6896—Neurological disorders, e.g. Alzheimer's disease
-
- 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
- A01K67/033—Rearing or breeding invertebrates; New breeds of invertebrates
- A01K67/0333—Genetically modified invertebrates, e.g. transgenic, polyploid
- A01K67/0335—Genetically modified worms
- A01K67/0336—Genetically modified Nematodes, e.g. Caenorhabditis elegans
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- G—PHYSICS
- G16—INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
- G16B—BIOINFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR GENETIC OR PROTEIN-RELATED DATA PROCESSING IN COMPUTATIONAL MOLECULAR BIOLOGY
- G16B20/00—ICT specially adapted for functional genomics or proteomics, e.g. genotype-phenotype associations
-
- 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
- A01K2227/703—Worms, e.g. Caenorhabdities elegans
-
- 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
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2500/00—Screening for compounds of potential therapeutic value
Definitions
- alpha-synuclein Mutant forms of alpha-synuclein are thought to increase the propensity for misfolding and induce other proteins to incorporate into the aggregates as well. Deficits in protein degrading enzymes may also contribute to protein accumulation, aggregation and alter cellular homeostasis. These aggregates are known as Lewy bodies and are comprised primarily of alpha-synuclein. They constitute the pathological hallmark of Parkinson's disease, Dementia with Lewy bodies and other neurodegenerative diseases. Lewy bodies are similar to the beta-amyloid plaques found in Alzheimer's patients. In fact, alpha-synuclein is also the largest component of these Alzheimer-related plaques.
- the present invention is directed to novel methods of using polynucleotide molecules and the proteins encoded by the molecules for use in diagnostic and treatment methods for neurological disorders characterized by neuron malfunction, neurodegeneration or protein misfolding and subsequent aggregation.
- a number of genes are described herein that affect the misfolding of, and subsequent aggregation of aggregation-prone proteins and have implications for the diagnosis and treatment of neurological diseases related to protein aggregation.
- the genes described herein result in an increase in protein misfolding and aggregation, specifically of alpha-synuclein when knocked down in an RNAi screen.
- Knowledge of genes relating to this process provides powerful means to develop diagnostic screening methods, mutation analysis and drug design information for the development of novel therapeutic and neuroprotective compounds.
- the claimed invention utilizes several suitable assays which can measure proteins that aggregate and cause neurological disease.
- Suitable assays encompass immunological methods, such as radioimmunoassay, enzyme-linked immunosorbent assays (ELISA), chemiluminescence assays and the like.
- the computer graphics systems enable prediction of how a new compound will link to the target molecule and allow experimental manipulation of the structures of the compound and target molecule to perfect binding specificity. Prediction of what the molecule-compound interaction will be when small changes are made in one or both requires molecular mechanics software and computationally intensive computers, usually coupled with user-friendly, menu- driven interfaces between the molecular design program and the user.
- the gene is expressed as a recombinant gene in a cell, so that the cells can be transplanted into a mammal, preferably a human in need of gene therapy.
- a genetic sequence which encodes for all or part of the gene is inserted into a vector and introduced into a host cell.
- expression of a defective or malfunctioning protein may be reduced using RNAi. Such methods are reviewed in Forte et al.(Curr Drug Targets. 2005 Feb;6(l):21-9).
Landscapes
- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Chemical & Material Sciences (AREA)
- Biotechnology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Health & Medical Sciences (AREA)
- Neurology (AREA)
- Medicinal Chemistry (AREA)
- Neurosurgery (AREA)
- Molecular Biology (AREA)
- Animal Behavior & Ethology (AREA)
- Organic Chemistry (AREA)
- Hematology (AREA)
- Immunology (AREA)
- Urology & Nephrology (AREA)
- Environmental Sciences (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Zoology (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Physics & Mathematics (AREA)
- Biochemistry (AREA)
- Microbiology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Analytical Chemistry (AREA)
- Food Science & Technology (AREA)
- Genetics & Genomics (AREA)
- Pathology (AREA)
- General Physics & Mathematics (AREA)
- Cell Biology (AREA)
- Animal Husbandry (AREA)
- Biodiversity & Conservation Biology (AREA)
- Wood Science & Technology (AREA)
- Psychology (AREA)
- General Engineering & Computer Science (AREA)
Abstract
Description
Claims
Priority Applications (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CA002599182A CA2599182A1 (en) | 2005-02-25 | 2006-02-27 | Regulators of protein misfolding and aggregation and methods of using the same |
JP2007557245A JP2008531019A (en) | 2005-02-25 | 2006-02-27 | Regulators of protein misfolding and aggregation and methods of using the regulators |
EP06736344A EP1856527A4 (en) | 2005-02-25 | 2006-02-27 | Regulators of protein misfolding and aggregation and methods of using the same |
AU2006216442A AU2006216442A1 (en) | 2005-02-25 | 2006-02-27 | Regulators of protein misfolding and aggregation and methods of using the same |
TW095131221A TW200801190A (en) | 2005-11-21 | 2006-08-24 | Regulators of protein misfolding and aggregation and methods of using the same |
Applications Claiming Priority (8)
Application Number | Priority Date | Filing Date | Title |
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US65633405P | 2005-02-25 | 2005-02-25 | |
US60/656,334 | 2005-02-25 | ||
US68189005P | 2005-05-17 | 2005-05-17 | |
US60/681,890 | 2005-05-17 | ||
US73876105P | 2005-11-21 | 2005-11-21 | |
US60/738,761 | 2005-11-21 | ||
US74991005P | 2005-12-12 | 2005-12-12 | |
US60/749,910 | 2005-12-12 |
Publications (3)
Publication Number | Publication Date |
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WO2006091964A2 true WO2006091964A2 (en) | 2006-08-31 |
WO2006091964A8 WO2006091964A8 (en) | 2007-03-22 |
WO2006091964A3 WO2006091964A3 (en) | 2007-07-12 |
Family
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PCT/US2006/007002 WO2006091964A2 (en) | 2005-02-25 | 2006-02-27 | Regulators of protein misfolding and aggregation and methods of using the same |
Country Status (7)
Country | Link |
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US (1) | US20070204352A1 (en) |
EP (1) | EP1856527A4 (en) |
JP (1) | JP2008531019A (en) |
KR (1) | KR20070110104A (en) |
AU (1) | AU2006216442A1 (en) |
CA (1) | CA2599182A1 (en) |
WO (1) | WO2006091964A2 (en) |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2009020624A1 (en) * | 2007-08-08 | 2009-02-12 | The Board Of Trustees Of The University Of Alabama For And On Behalf Of The University Of Alabama | Regulators of protein misfolding and neuroprotection and methods of use |
WO2011137486A1 (en) * | 2010-05-04 | 2011-11-10 | Monash University | Diagnostic and prognostic and therapeutic methods |
US9340779B2 (en) | 2010-08-30 | 2016-05-17 | Imba—Institut Für Molekulare Biotechnologie Gmbh | Use of a HSPC117 molecule as RNA ligase |
Families Citing this family (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP2042592A1 (en) * | 2007-09-28 | 2009-04-01 | IMBA-Institut für Molekulare Biotechnologie GmbH | Methods for modulating the proliferation and differentiation potential of stem cells and progenitor cells |
IT1405762B1 (en) | 2010-11-25 | 2014-01-24 | Icgeb | RECOMBINANT PROTEINS WITH SELECTIVE TARGET INACTIVITY ACTIVITIES |
WO2012178183A1 (en) * | 2011-06-24 | 2012-12-27 | Board Of Regents, The University Of Texas System | Human age-related neurodegenerative nematode model and methods |
US9296994B2 (en) | 2012-04-23 | 2016-03-29 | Imba-Institut Für Molekulare Biotechnologie Gmbh | Archease as RNA ligaes complex member |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CA2294472C (en) * | 1997-06-19 | 2010-06-15 | The General Hospital Corporation | Torsin, torsin genes, and methods of use |
US20050214763A1 (en) * | 2002-02-14 | 2005-09-29 | Rainer Hipfel | Diagnostic and therapeutic use of an activator protein for vesicle secretion for neurodegenerative diseases |
US20030235823A1 (en) * | 2002-06-24 | 2003-12-25 | The University Of Alabama | Nucleotide sequences that code for torsin genes, torsin proteins, and methods of using the same to treat protein-aggregation |
-
2006
- 2006-02-27 WO PCT/US2006/007002 patent/WO2006091964A2/en active Application Filing
- 2006-02-27 KR KR1020077021968A patent/KR20070110104A/en not_active Application Discontinuation
- 2006-02-27 JP JP2007557245A patent/JP2008531019A/en active Pending
- 2006-02-27 US US11/364,612 patent/US20070204352A1/en not_active Abandoned
- 2006-02-27 EP EP06736344A patent/EP1856527A4/en not_active Withdrawn
- 2006-02-27 AU AU2006216442A patent/AU2006216442A1/en not_active Abandoned
- 2006-02-27 CA CA002599182A patent/CA2599182A1/en not_active Abandoned
Non-Patent Citations (1)
Title |
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See references of EP1856527A4 * |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2009020624A1 (en) * | 2007-08-08 | 2009-02-12 | The Board Of Trustees Of The University Of Alabama For And On Behalf Of The University Of Alabama | Regulators of protein misfolding and neuroprotection and methods of use |
WO2011137486A1 (en) * | 2010-05-04 | 2011-11-10 | Monash University | Diagnostic and prognostic and therapeutic methods |
US9340779B2 (en) | 2010-08-30 | 2016-05-17 | Imba—Institut Für Molekulare Biotechnologie Gmbh | Use of a HSPC117 molecule as RNA ligase |
Also Published As
Publication number | Publication date |
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US20070204352A1 (en) | 2007-08-30 |
AU2006216442A1 (en) | 2006-08-31 |
WO2006091964A8 (en) | 2007-03-22 |
CA2599182A1 (en) | 2006-08-31 |
EP1856527A4 (en) | 2010-09-01 |
EP1856527A2 (en) | 2007-11-21 |
JP2008531019A (en) | 2008-08-14 |
WO2006091964A3 (en) | 2007-07-12 |
KR20070110104A (en) | 2007-11-15 |
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