Title:
METHODS AND COMPOSITIONS FOR TREATING OR PREVENTING OBESITY-RELATED DISORDERS BY OPSIN 3 REGULATION OF HYPOTHALAMIC MELANOCORTIN RECEPTORS
Document Type and Number:
WIPO Patent Application WO/2021/062124
Kind Code:
A3
Abstract:
Described herein are methods and compositions for the prevention or treatment of obesity and obesity-related disorders. The methods and compositions are based, inter alia, on the observations that OPN3 is the most highly expressed opsin in the hypothalamus, a key site for the regulation of energy homeostasis. Indeed, OPN3 expression was highest in regions associated with energy homeostasis, namely the paraventricular nucleus and arcuate nucleus of the hypothalamus. OPN3 was shown to interact and form a complex with MC3R and MC4R, and to modulate MC3R- and MC4R-mediated signaling in the hypothalamus. Accordingly, the methods involve the regulation of melanocortin receptors by down regulating opsin 3 (OPN3) protein expression, OPN3 gene expression, and/or OPN3 activation in the hypothalamus.
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Inventors:
OANCEA ELENA (US)
Application Number:
PCT/US2020/052676
Publication Date:
May 14, 2021
Filing Date:
September 25, 2020
Export Citation:
Assignee:
UNIV BROWN (US)
International Classes:
A61K48/00; A61K38/00; A61K38/46; C07H21/04; C12N15/00; C12N15/11
Foreign References:
| US20150057334A1 | 2015-02-26 | |||
| US20130011850A1 | 2013-01-10 | |||
| US20120164148A1 | 2012-06-28 | |||
| US20130309254A1 | 2013-11-21 |
Other References:
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ORTIZ ET AL.: "Opsin 3 and 4 mediate light-induced pulmonary vasorelaxation that is potentiated by G protein-coupled receptor kinase 2 inhibition", AM J PHYSIOL LUNG CELL MOL PHYSIOL., vol. 314, no. 1, 2018, pages L93 - L106
OZDESLIK ET AL.: "Human nonvisual opsin 3 regulates pigmentation of epidermal melanocytes through functional interaction with melanocortin 1 receptor", PROC NATL ACAD SCI USA., vol. 116, no. 23, June 2019 (2019-06-01), pages 11508 - 11517, XP055822463
SLOBODA ET AL.: "Fatty Acids Impair Endothelium-Dependent Vasorelaxation: A Link Between Obesity and Arterial Stiffness in Very Old Zucker Rats", J GERONTOL A BIOL SCI MED SCI., vol. 67, no. 9, 2012, pages 927 - 38, XP055822466
NAYAK ET AL.: "Adaptive Thermogenesis in Mice Is Enhanced by Opsin 3-Dependent Adipocyte Light Sensing", CELL REP., vol. 30, no. 3, 2020, pages 672 - 686, XP055822467
SATO ET AL.: "Cell -autonomous light sensitivity via Opsin3 regulates fuel utilization in brown adipocytes", PLOS BIOL., vol. 18, no. 2, February 2020 (2020-02-01), pages e3000630
ORTIZ ET AL.: "Opsin 3 and 4 mediate light-induced pulmonary vasorelaxation that is potentiated by G protein-coupled receptor kinase 2 inhibition", AM J PHYSIOL LUNG CELL MOL PHYSIOL., vol. 314, no. 1, 2018, pages L93 - L106
OZDESLIK ET AL.: "Human nonvisual opsin 3 regulates pigmentation of epidermal melanocytes through functional interaction with melanocortin 1 receptor", PROC NATL ACAD SCI USA., vol. 116, no. 23, June 2019 (2019-06-01), pages 11508 - 11517, XP055822463
SLOBODA ET AL.: "Fatty Acids Impair Endothelium-Dependent Vasorelaxation: A Link Between Obesity and Arterial Stiffness in Very Old Zucker Rats", J GERONTOL A BIOL SCI MED SCI., vol. 67, no. 9, 2012, pages 927 - 38, XP055822466
NAYAK ET AL.: "Adaptive Thermogenesis in Mice Is Enhanced by Opsin 3-Dependent Adipocyte Light Sensing", CELL REP., vol. 30, no. 3, 2020, pages 672 - 686, XP055822467
SATO ET AL.: "Cell -autonomous light sensitivity via Opsin3 regulates fuel utilization in brown adipocytes", PLOS BIOL., vol. 18, no. 2, February 2020 (2020-02-01), pages e3000630
Attorney, Agent or Firm:
HOLMANDER, Daniel, J. et al. (US)
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