Modulation de la survie des cellules en modulant la fonction de huntingtin

Modulating cell survival by modulating huntingtin function

Abstract

The present invention provides a means of modulating cell survival by modulating wild-type huntingtin protein function by administration of wild-type huntingtin protein, biologically active fragments thereof and/or antagonists of wild-type huntingtin. Accordingly, the present invention also provides biologically active fragments of wild-type huntingtin, antagonists of wild-type huntingtin and nucleic acid sequences encoding the biologically active fragments and peptide antagonists, and their use to modulate cell survival. In particular, the invention provides for means to activate or attenuate cell death within tissue, in order to facilitate the treatment of conditions where there is a dysregulation of cell death or cellular proliferation. Therapeutic application of this invention pertains to diseases and disorders including, but not limited to, Huntington disease, neurodegenerative diseases, stroke, and cancer.
La présente invention porte sur un moyen de moduler la survie des cellules en modulant la fonction de la protéine huntingtin de type sauvage et en administrant cette protéine, ses fragments biologiquement actifs et/ou ses antagonistes. Cette invention porte donc également sur des fragments biologiquement actifs de la protéine huntingtin de type sauvage, sur ses antagonistes et sur des séquences d'acide nucléique codant les fragments biologiquement actifs et les antagonistes peptidiques, et sur leur utilisation pour moduler la survie des cellules. Cette invention porte notamment sur un moyen d'activation ou d'atténuation de la mort cellulaire dans les tissus afin de faciliter le traitement d'états pathologiques présentant un dérèglement de la mort cellulaire ou de la prolifération cellulaire. Les applications thérapeutiques de cette invention se rapportent aux maladies ou troubles tels que notamment, mais pas exclusivement, la maladie de Huntington, les maladies dégénératives, les accidents cérébrovasculaires et le cancer.

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Patent Citations (7)

    Publication numberPublication dateAssigneeTitle
    EP-0614977-A2September 14, 1994The General Hospital CorporationADN-Huntingtin, protéine et utilisation
    WO-0078813-A2December 28, 2000Emory UniversityHuntington disease cellular model: stably transfected pc12 cells expressing mutant huntingtin
    WO-0106989-A2February 01, 2001Abgenix, Inc., New York State Department Of HealthProcedes et compositions permettant d'inhiber l'accumulation des polypeptides associee aux troubles neurologiques
    WO-0109613-A1February 08, 2001Fondation Jean Dausset-CephMethod for screening molecules for the treatment of huntington disease
    WO-9906545-A2February 11, 1999MAX-PLANCK-Gesellschaft zur Förderung der Wissenschaften e.V.Composition et nouveau procede pour depister les maladies dues a la formation d'agregats de proteines ou de fibrilles du type amyloide
    WO-9945944-A1September 16, 1999The Burnham InstitutePeptides proapoptotiques, polypeptides de dependance, et mode d'utilisation
    WO-9960986-A2December 02, 1999University Of British Columbia, Merck Frosst Canada & Co.Modulateurs d'apoptose interagissant avec le gene de la maladie de huntington

NO-Patent Citations (4)

    Title
    HEISER VOLKER ET AL: "Inhibition of huntingtin fibrillogenesis by specific antibodies and small molecules: Implications for Huntington's disease therapy", PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF USA, NATIONAL ACADEMY OF SCIENCE. WASHINGTON, US, vol. 97, no. 12, 6 June 2000 (2000-06-06), pages 6739 - 6744, XP002155981, ISSN: 0027-8424
    KIM M ET AL: "MUTANT HUNTINGTIN EXPRESSION IN CLONAL STRIATAL CELLS: DISSOCIATIONOF INCLUSION FORMATION AND NEURONAL SURVIVAL BY CASPASE INHIBITION", JOURNAL OF NEUROSCIENCE, NEW YORK, NY, US, vol. 19, no. 3, 1 February 1999 (1999-02-01), pages 964 - 973, XP000973324, ISSN: 0270-6474
    LEAVITT B.R. ET AL.: "Wild-Type Huntingtin Reduces the Cellular Toxicity of Mutant Huntingtin In Vivo", AM. J. HUM. GENETICS, vol. 68, 2001, pages 313 - 324, XP001013155
    RIGAMONTI D., ET AL.: "Wild-Type Huntingtin Protects from Apoptosis Upstream of Caspase 3", THE JOURNAL OF NEUROSCIENCE, vol. 20, no. 10, 15 May 2000 (2000-05-15), pages 3705 - 3713, XP002174028

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