Title:
METHOD TO IMPROVE NEUROLOGIC OUTCOMES IN TEMPERATURE MANAGED PATIENTS
Document Type and Number:
WIPO Patent Application WO/2016/187558
Kind Code:
A3
Abstract:
A method of improving brain function in a hypothermic patient is provided. The method comprises administering to the patient an amount of a fibroblast growth factor 21 (FGF21) effective to increase RNA binding motif 3 (RBM3) production in nerve cells of the patient. The method is useful, for example, where the patient is or will be undergoing cardiac surgery or spinal surgery, such as requiring deep hypothermia circulatory arrest (DHCA), or is subject to an emergency preservation and resuscitation (EPR) method, or where a patient suffers from mild/moderate/severe traumatic brain injury (TBI), ventricular fibrillation cardiac arrest (VFCA), subarachnoid hemorrhage (SAH), subdural hematoma (SH), cerebral vasospasm, neonatal abusive head trauma (a.k.a. shaken baby syndrome), neonatal hypoxic ischemic encephalopathy (HIE), asphyxia cardiac arrest (ACA), treatment of spinal injury, prophylaxis in spinal surgery, stroke, and drug overdose.
Inventors:
JACKSON TRAVIS C (US)
KOCHANEK PATRICK M (US)
KOCHANEK PATRICK M (US)
Application Number:
PCT/US2016/033563
Publication Date:
January 12, 2017
Filing Date:
May 20, 2016
Export Citation:
Assignee:
UNIV OF PITTSBURGH-OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION (US)
International Classes:
A61K38/18; A61P25/00; C07K14/50
Foreign References:
| US20020091431A1 | 2002-07-11 | |||
| US6156057A | 2000-12-05 |
Other References:
CHIP ET AL.: "The RNA-binding protein RBM3 is involved in hypothermia induced neuroprotection.", vol. 43, no. Issue 2, 17 April 2011 (2011-04-17), pages 388 - 396, XP055346051
KERN ET AL.: "The Effects of Temperature and Seasons on Subcutaneous White Adipose Tissue in Humans: Evidence for Thermogenic Gene Induction.", J CLIN. ENDOCRINOL. METAB., vol. 99, no. Issue 12, 31 December 2014 (2014-12-31), pages E2772 - e2779, XP055346058
DOURIS ET AL.: "Central Fibroblast Growth Factor 21 Browns White Fat via Sympathetic Action in Male Mice.", ENDOCRINOLOGY., vol. 156, no. Issue 7, 29 April 2015 (2015-04-29), pages 2470 - 81, XP055346067
GAICH ET AL.: "The Effects of LY2405319, an FGF21 Analog, in Obese Human Subjects with Type 2 Diabetes.", CELL METAB., vol. 18, no. Issue 3, 3 September 2013 (2013-09-03), pages 333 - 40, XP055346070
JACKSON ET AL.: "Cold stress protein RBM3 responds to temperature change in an ultra- sensitive manner in young neurons.", NEUROCIENCE., vol. 305, 8 August 2015 (2015-08-08), pages 268 - 78, XP029261830
FISHER ET AL.: "FGF21 regulates PGC-1alpha and browning of white adipose tissues in adaptive thermogenesis", GENES DEV., vol. 26, no. 3, 1 February 2012 (2012-02-01), pages 271 - 281, XP055160186
KERN ET AL.: "The Effects of Temperature and Seasons on Subcutaneous White Adipose Tissue in Humans: Evidence for Thermogenic Gene Induction.", J CLIN. ENDOCRINOL. METAB., vol. 99, no. Issue 12, 31 December 2014 (2014-12-31), pages E2772 - e2779, XP055346058
DOURIS ET AL.: "Central Fibroblast Growth Factor 21 Browns White Fat via Sympathetic Action in Male Mice.", ENDOCRINOLOGY., vol. 156, no. Issue 7, 29 April 2015 (2015-04-29), pages 2470 - 81, XP055346067
GAICH ET AL.: "The Effects of LY2405319, an FGF21 Analog, in Obese Human Subjects with Type 2 Diabetes.", CELL METAB., vol. 18, no. Issue 3, 3 September 2013 (2013-09-03), pages 333 - 40, XP055346070
JACKSON ET AL.: "Cold stress protein RBM3 responds to temperature change in an ultra- sensitive manner in young neurons.", NEUROCIENCE., vol. 305, 8 August 2015 (2015-08-08), pages 268 - 78, XP029261830
FISHER ET AL.: "FGF21 regulates PGC-1alpha and browning of white adipose tissues in adaptive thermogenesis", GENES DEV., vol. 26, no. 3, 1 February 2012 (2012-02-01), pages 271 - 281, XP055160186
Attorney, Agent or Firm:
HIRSHMAN, Jesse, A. et al. (US)
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