Title:
METHODS AND COMPOSITIONS FOR THE IDENTIFICATION AND TREATMENT OF NEURODEGENERATIVE DISORDERS
Document Type and Number:
WIPO Patent Application WO2002058626
Kind Code:
A3
Abstract:
The present invention relates to Drosophila models of the neurodegenerative disorder spinocerebellar ataxia 1 (SCA-1). In particular, the invention relates to transgenic Drosophila which express normal human ataxin-1 or mutant human ataxin-1 with expanded polyglutamine repeats for SCA-1 therapeutics. The invention further relates to the diagnosis of predispositions to developing SCA-1. The invention further relates to methods of using the transgenic Drosophila to screen for therapeutics of SCA-1 and other neurodegenerative disorders. The invention further relates to the identification of modifier genes of the SCA-1 phenotypes produced by overexpression of ataxin-1, for therapeutic and diagnostic uses and for screening for therapeutics of SCA-1 and other neurodegenerative disorders. The invention further relates to the diagnosis of a predisposition to SCA-1 comprising detecting the overexpression of normal ataxin-1.
Inventors:
BOTAS JUAN
ZOGHBI HUDA
MARTINEZ PEDRO
FERNANDEZ-FUNEZ PEDRO
NINO-ROSALES MARIA LAURA
GOUYON BEATRICE DE
SHE WEI-CHI
LUCHAK JAMES
ZOGHBI HUDA
MARTINEZ PEDRO
FERNANDEZ-FUNEZ PEDRO
NINO-ROSALES MARIA LAURA
GOUYON BEATRICE DE
SHE WEI-CHI
LUCHAK JAMES
Application Number:
PCT/US2001/049564
Publication Date:
August 14, 2003
Filing Date:
October 29, 2001
Export Citation:
Assignee:
BAYLOR COLLEGE MEDICINE (US)
International Classes:
A01K67/033; A61K31/7088; A61K31/7105; A61K38/00; A61K39/395; A61K45/00; A61K48/00; A61P9/00; A61P9/12; A61P21/00; A61P21/04; A61P25/00; A61P25/02; A61P25/08; A61P25/16; A61P25/18; A61P25/28; A61P25/32; A61P27/02; A61P27/06; A61P31/18; A61P35/00; A61P39/04; C07K14/47; C12N15/09; C12N15/12; C12Q1/02; C12Q1/68; G01N33/15; G01N33/50; (IPC1-7): G01N33/00; A01K43/04; A01K61/00; A01K67/027; C12Q1/68; A01K38/00
Other References:
WARRICK J.M. ET AL.: "Suppression of polyglutamine-mediated neurodegeneration in drosophila by the molecular chaperone HSP70", NATURE GENETICS, vol. 23, December 1999 (1999-12-01), pages 425 - 428, XP002963929
WARRICK J.M. ET AL.: "Expanded polyglutamine protein forms nuclear inclusions and causes neural degeneration in drosophila", CELL, vol. 93, 12 June 1998 (1998-06-12), pages 939 - 949, XP002203976
CLARK H. BRENT ET AL.: "Spinocerebellar ataxia type 1 - modeling the pathogenesis of a polyglutamine neurodegenerative disorder in transgenic mice", JOURNAL OF NEUROPATHOLOGY EXPERIMENTAL NEUROLOGY, vol. 59, no. 4, April 2000 (2000-04-01), pages 265 - 270, XP002963930
BURRIGHT E.N. ET AL.: "SCA1 transgenic mice: a model for neurodegeneration caused by an expanded CAG trinucleotide repeat", CELL, vol. 82, 22 September 1995 (1995-09-22), pages 937 - 948, XP002913537
MANGIARINI L. ET AL.: "Instability of highly expanded CAG repeats in mice transgenic for the Huntington's disease mutation", NATURE GENETICS, vol. 15, 15 February 1997 (1997-02-15), pages 197 - 200, XP002965112
MERRY D.E. ET AL.: "Characterization of transgenic model for SBMA", AMERICAN JOURNAL OF HUMAN GENETICS, vol. 65, no. 4, October 1999 (1999-10-01), pages A30, ABS. 153, XP002963931
DAVIES S.W. ET AL.: "Formation of neuronal intranuclear inclusions underlies the neurological dysfunction in mice transgenic for the HD mutation", CELL, vol. 90, 8 August 1997 (1997-08-08), pages 537 - 548, XP002158908
TIMCHENKO L.T. ET AL.: "Triplet repeat disorders: discussion of molecular mechanisms", CELL MOL. LIFE SCI., vol. 55, 1995, pages 1432 - 1447, XP002963932
BATES G.P. ET AL.: "Transgenic mouse models of neurodegenerative disease caused by CAG/polyglutamine expansions", MOLEC. MED. TODAY, November 1997 (1997-11-01), pages 508 - 515, XP002963933
See also references of EP 1356278A4
WARRICK J.M. ET AL.: "Expanded polyglutamine protein forms nuclear inclusions and causes neural degeneration in drosophila", CELL, vol. 93, 12 June 1998 (1998-06-12), pages 939 - 949, XP002203976
CLARK H. BRENT ET AL.: "Spinocerebellar ataxia type 1 - modeling the pathogenesis of a polyglutamine neurodegenerative disorder in transgenic mice", JOURNAL OF NEUROPATHOLOGY EXPERIMENTAL NEUROLOGY, vol. 59, no. 4, April 2000 (2000-04-01), pages 265 - 270, XP002963930
BURRIGHT E.N. ET AL.: "SCA1 transgenic mice: a model for neurodegeneration caused by an expanded CAG trinucleotide repeat", CELL, vol. 82, 22 September 1995 (1995-09-22), pages 937 - 948, XP002913537
MANGIARINI L. ET AL.: "Instability of highly expanded CAG repeats in mice transgenic for the Huntington's disease mutation", NATURE GENETICS, vol. 15, 15 February 1997 (1997-02-15), pages 197 - 200, XP002965112
MERRY D.E. ET AL.: "Characterization of transgenic model for SBMA", AMERICAN JOURNAL OF HUMAN GENETICS, vol. 65, no. 4, October 1999 (1999-10-01), pages A30, ABS. 153, XP002963931
DAVIES S.W. ET AL.: "Formation of neuronal intranuclear inclusions underlies the neurological dysfunction in mice transgenic for the HD mutation", CELL, vol. 90, 8 August 1997 (1997-08-08), pages 537 - 548, XP002158908
TIMCHENKO L.T. ET AL.: "Triplet repeat disorders: discussion of molecular mechanisms", CELL MOL. LIFE SCI., vol. 55, 1995, pages 1432 - 1447, XP002963932
BATES G.P. ET AL.: "Transgenic mouse models of neurodegenerative disease caused by CAG/polyglutamine expansions", MOLEC. MED. TODAY, November 1997 (1997-11-01), pages 508 - 515, XP002963933
See also references of EP 1356278A4
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