WO1999060986A3 - Apoptosis modulators that interact with the huntington's disease gene - Google Patents

Apoptosis modulators that interact with the huntington's disease gene Download PDF

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Publication number
WO1999060986A3
WO1999060986A3 PCT/US1999/011743 US9911743W WO9960986A3 WO 1999060986 A3 WO1999060986 A3 WO 1999060986A3 US 9911743 W US9911743 W US 9911743W WO 9960986 A3 WO9960986 A3 WO 9960986A3
Authority
WO
WIPO (PCT)
Prior art keywords
hip
protein
huntingtin
hip1
ded
Prior art date
Legal status (The legal status 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 status listed.)
Ceased
Application number
PCT/US1999/011743
Other languages
French (fr)
Other versions
WO1999060986A2 (en
Inventor
Michael Kalchman
Michael R Hayden
Abigail Hackam
Vikramjit Chopra
Donald W Nicholson
John P Vallaincourt
Dita M Rasper
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
University of British Columbia
Merck Frosst Canada and Co
Original Assignee
University of British Columbia
Merck Frosst Canada and Co
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 University of British Columbia, Merck Frosst Canada and Co filed Critical University of British Columbia
Priority to EP99925933A priority Critical patent/EP1082336A4/en
Priority to AU42121/99A priority patent/AU4212199A/en
Priority to CA002329249A priority patent/CA2329249A1/en
Priority to JP2000550447A priority patent/JP2002516075A/en
Publication of WO1999060986A2 publication Critical patent/WO1999060986A2/en
Publication of WO1999060986A3 publication Critical patent/WO1999060986A3/en
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • 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
    • 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
    • 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
    • C07K14/4747—Apoptosis related proteins
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides

Landscapes

  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Molecular Biology (AREA)
  • Genetics & Genomics (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Biophysics (AREA)
  • Biochemistry (AREA)
  • Toxicology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Zoology (AREA)
  • Immunology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Engineering & Computer Science (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Peptides Or Proteins (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

A family of proteins, including a specific human protein designated as HIP1, has been identified that interact differently with the gene product of a normal (16 CAG repeat) and an expanded (⊃44 CAG repeat) HD gene. Expression of the HIP1 protein was found to be enriched in the brain. Analysis of the sequence of the HIP1 protein indicated that it includes a death effector domain (DED), suggesting an apoptotic function. Thus, it appears that a normal function of Huntingtin may be to bind HIP1 and related apoptosis modulators, reducing its effectiveness in stimulating cell death. Since expanded huntingtin performs this function less well, there is an increase in HIP1-modulated cell death in individuals with an expanded repeat in the HD gene. This understanding of the likely role of huntingtin and HIP1 or related proteins (collectively 'HIP-apoptosis modulating proteins') in the pathology of Huntington's disease offers several possibilities for therapy. First, because the function of huntingtin apparently depends at least in part on the ability to interact with HIP-apoptosis modulating proteins, added expression (e.g., via gene therapy) of normal (non-expanded) huntingtin or of the HIP-binding region of huntingtin should provide a therapeutic benefit. Other DED-interacting peptides could also be used to mask and reduce the interaction of HIP-apoptosis modulating proteins with the death signaling complex. Alternatively, a mutant form of HIP-protein from which the DED has been deleted might be introduced, for example using gene therapy techniques. Because HIP-apoptosis modulating proteins have been shown to self-associate, a protein with a deleted DED may compete with endogenous HIP-protein in the formation of these associations, thereby reducing the amount of apoptotically-active HIP-protein.
PCT/US1999/011743 1998-05-27 1999-05-27 Apoptosis modulators that interact with the huntington's disease gene Ceased WO1999060986A2 (en)

Priority Applications (4)

Application Number Priority Date Filing Date Title
EP99925933A EP1082336A4 (en) 1998-05-27 1999-05-27 APOPTOSEMODULATORS THAT RESPOND WITH THE GENE OF HUNTINGTON'S DISEASE
AU42121/99A AU4212199A (en) 1998-05-27 1999-05-27 Apoptosis modulators that interact with the huntington's disease gene
CA002329249A CA2329249A1 (en) 1998-05-27 1999-05-27 Apoptosis modulators that interact with the huntington's disease gene
JP2000550447A JP2002516075A (en) 1998-05-27 1999-05-27 Apoptosis modulator interacts with Huntington's disease gene

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US09/085,199 1998-05-27
US09/085,199 US6235879B1 (en) 1995-11-17 1998-05-27 Apoptosis modulators that interact with the Huntington's disease gene

Publications (2)

Publication Number Publication Date
WO1999060986A2 WO1999060986A2 (en) 1999-12-02
WO1999060986A3 true WO1999060986A3 (en) 2000-04-20

Family

ID=22190103

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1999/011743 Ceased WO1999060986A2 (en) 1998-05-27 1999-05-27 Apoptosis modulators that interact with the huntington's disease gene

Country Status (6)

Country Link
US (1) US6235879B1 (en)
EP (1) EP1082336A4 (en)
JP (1) JP2002516075A (en)
AU (1) AU4212199A (en)
CA (1) CA2329249A1 (en)
WO (1) WO1999060986A2 (en)

Families Citing this family (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7595199B1 (en) * 1998-07-31 2009-09-29 Max-Planck-Gesellschaft zur Förderung der Wissenchaften e.V. Method of detecting amyloid-like fibrils or protein aggregates
WO2001079283A1 (en) * 2000-04-13 2001-10-25 University Of British Columbia Modulating cell survival by modulating huntingtin function
US6738105B1 (en) * 2000-11-02 2004-05-18 Intel Corporation Coherent light despeckling
US20020133841A1 (en) * 2000-12-11 2002-09-19 Leviten Michael W. Transgenic mice containing huntingtin interacting protein gene disruptions
US7033790B2 (en) 2001-04-03 2006-04-25 Curagen Corporation Proteins and nucleic acids encoding same
US6794501B2 (en) 2001-05-04 2004-09-21 Ludwig Institute For Cancer Research Colon cancer antigen panel
US7803382B2 (en) 2001-05-04 2010-09-28 Ludwig Institute For Cancer Research Ltd. Method for inducing immune response to NY-CO-58
US7429450B2 (en) * 2001-11-15 2008-09-30 The Regents Of The University Of Michigan HIP1 cancer markers
US7790384B2 (en) * 2001-11-15 2010-09-07 The Regents Of The University Of Michigan HIP1 cancer markers
US20040265929A1 (en) * 2001-11-15 2004-12-30 The Regents Of The University Of Michigan Humoral response to HIP1 in cancer
EP1636362A2 (en) * 2003-06-20 2006-03-22 Max-Planck-Gesellschaft Zur Förderung Der Wissenschaften E.V. Disease related protein network
WO2009134405A2 (en) * 2008-04-30 2009-11-05 Siemens Medical Solutions Usa, Inc. Novel substrate based pet imaging agents
CN108840923B (en) * 2018-06-22 2021-08-03 上海交通大学医学院附属仁济医院 A kind of polypeptide targeting PD-L1 and its application

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1997018825A1 (en) * 1995-11-17 1997-05-29 The University Of British Columbia PROTEIN WHICH INTERACTS WITH THE HUNTINGTON'S DISEASE GENE PRODUCT, cDNA CODING THEREFOR, AND ANTIBODIES THERETO

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
See also references of EP1082336A4 *
WANKER ET AL.: "HIP-I: A Huntingtin Interacting Protein Isolated by the Yeast Two-Hybrid System", HUMAN MOLECULAR GENETICS, vol. 6, no. 3, March 1997 (1997-03-01), pages 487 - 495, XP002925327 *

Also Published As

Publication number Publication date
CA2329249A1 (en) 1999-12-02
US6235879B1 (en) 2001-05-22
AU4212199A (en) 1999-12-13
EP1082336A4 (en) 2005-01-19
EP1082336A2 (en) 2001-03-14
WO1999060986A2 (en) 1999-12-02
JP2002516075A (en) 2002-06-04

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