Title:
THERAPEUTIC AGENT FOR DISEASES ASSOCIATED WITH ABNORMALITIES IN DYSTROGLYCAN SUGAR CHAIN MODIFICATION AND METHOD FOR ASSAYING ASSOCIATED ENZYME
Document Type and Number:
WIPO Patent Application WO/2018/034334
Kind Code:
A1
Abstract:
Provided is a therapeutic agent which effectively acts on diseases associated with abnormalities in dystroglycan sugar chain modification. A method for diagnosing diseases associated with abnormalities in dystroglycan sugar chain modification is also provided. This therapeutic agent for diseases associated with abnormalities in dystroglycan sugar chain modification contains CDP-ribitol as an active ingredient. Ribitol phosphate is important in the sugar chain structure of dystroglycan, and a material (sugar donor) is required for ribitol phosphate to be incorporated in the sugar chain of dystroglycan. In the present invention, it is revealed for the first time that CDP-ribitol functions as a sugar donor. After observing that sugar chains of ISPD-deficient cells could be recovered by administering CDP-ribitol, the present invention was conceived in which CDP-ribitol can be used for replacement therapy.
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Inventors:
TODA TATSUSHI (JP)
KOBAYASHI KAZUHIRO (JP)
KANAGAWA MOTOI (JP)
ENDO TAMAO (JP)
MANYA HIROSHI (JP)
WADA YOSHINAO (JP)
TAJIRI MICHIKO (JP)
KOBAYASHI KAZUHIRO (JP)
KANAGAWA MOTOI (JP)
ENDO TAMAO (JP)
MANYA HIROSHI (JP)
WADA YOSHINAO (JP)
TAJIRI MICHIKO (JP)
Application Number:
PCT/JP2017/029600
Publication Date:
February 22, 2018
Filing Date:
August 18, 2017
Export Citation:
Assignee:
UNIV KOBE NAT UNIV CORP (JP)
TOKYO METROPOLITAN GERIATRIC HOSPITAL AND INST OF GERONTOLOGY (JP)
OSAKA PREFECTURAL HOSPITAL ORGANIZATION (JP)
TOKYO METROPOLITAN GERIATRIC HOSPITAL AND INST OF GERONTOLOGY (JP)
OSAKA PREFECTURAL HOSPITAL ORGANIZATION (JP)
International Classes:
A61K31/7068; A61P21/00; A61P43/00; C07K7/08; G01N33/50
Other References:
GERIN, ISABELLE ET AL.: "ISPD produces CDP-ribitol used by FKTN and FKRP to transfer ribitol phosphate onto a-dystroglycan", NATURE COMMUNICATIONS, vol. 7, no. 1, May 2016 (2016-05-01), pages 1 - 15, XP055603582, DOI: 10.1038/ncomms11534
TATSUSHI TODA ET AL.: "Medical syndromes of muscular diseases", JAPANESE JOURNAL OF CLINICAL MEDICINE, no. 32, May 2015 (2015-05-01), pages 135 - 145
KUWABARA, NAOYUKI ET AL.: "Carbohydrate-binding domain of the POMGnTl stem region modulates O-mannosylation sites of a-dystroglycan", PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF UNITED STATES OF AMERICA, vol. 113, no. 33, 16 August 2016 (2016-08-16), pages 9280 - 9285, XP055603603, ISSN: 0027-8424, DOI: 10.1073/pnas.1525545113
KOBAYASHI, KAZUHIRO ET AL.: "An ancient retrotransposal insertion causes Fukuyama-type congenital muscular dystrophy", NATURE, vol. 394, 1998, pages 388 - 392, XP055603609, ISSN: 0028-0836, DOI: 10.1038/28653
LU , PEI J. ET AL.: "Mutations alter secretion of fukutin-related protein", BIOCHIMICA ET BIOPHYSICA ACTA, vol. 1802, 2010, pages 253 - 258, XP026857118
KANAGAWA, MOTOI ET AL.: "Identification of a Post-translational Modification with Ribitol-Phosphate and Its Defect in Muscular Dystrophy", CELL REPORTS, vol. 14, no. 9, March 2016 (2016-03-01), pages 2209 - 2223, XP029720470, ISSN: 2211-1247, DOI: 10.1016/j.celrep.2016.02.017
26 February 2016 (2016-02-26), Retrieved from the Internet [retrieved on 20170907]
WALKER-WARBURG (WWS, May 2015 (2015-05-01), pages 150 - 153
PRAISSMAN, JEREMY L ET AL.: "The functional 0-mannose glycan on a-dystroglycan contains a phospho-ribitol primed for matriglycan addition", ELIFE, vol. 5, no. e14473, April 2016 (2016-04-01), pages 1 - 28, XP055603613, DOI: 10.7554/eLife.14473
TATSUSHI TODA ET AL.: "Medical syndromes of muscular diseases", JAPANESE JOURNAL OF CLINICAL MEDICINE, no. 32, May 2015 (2015-05-01), pages 135 - 145
KUWABARA, NAOYUKI ET AL.: "Carbohydrate-binding domain of the POMGnTl stem region modulates O-mannosylation sites of a-dystroglycan", PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF UNITED STATES OF AMERICA, vol. 113, no. 33, 16 August 2016 (2016-08-16), pages 9280 - 9285, XP055603603, ISSN: 0027-8424, DOI: 10.1073/pnas.1525545113
KOBAYASHI, KAZUHIRO ET AL.: "An ancient retrotransposal insertion causes Fukuyama-type congenital muscular dystrophy", NATURE, vol. 394, 1998, pages 388 - 392, XP055603609, ISSN: 0028-0836, DOI: 10.1038/28653
LU , PEI J. ET AL.: "Mutations alter secretion of fukutin-related protein", BIOCHIMICA ET BIOPHYSICA ACTA, vol. 1802, 2010, pages 253 - 258, XP026857118
KANAGAWA, MOTOI ET AL.: "Identification of a Post-translational Modification with Ribitol-Phosphate and Its Defect in Muscular Dystrophy", CELL REPORTS, vol. 14, no. 9, March 2016 (2016-03-01), pages 2209 - 2223, XP029720470, ISSN: 2211-1247, DOI: 10.1016/j.celrep.2016.02.017
26 February 2016 (2016-02-26), Retrieved from the Internet
WALKER-WARBURG (WWS, May 2015 (2015-05-01), pages 150 - 153
PRAISSMAN, JEREMY L ET AL.: "The functional 0-mannose glycan on a-dystroglycan contains a phospho-ribitol primed for matriglycan addition", ELIFE, vol. 5, no. e14473, April 2016 (2016-04-01), pages 1 - 28, XP055603613, DOI: 10.7554/eLife.14473
Attorney, Agent or Firm:
SHOJI, Takashi et al. (JP)
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