Method to Improve Neurologic Outcomes in Temperature Managed Patients

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.

We claim: 
     
         1 . A method of treating cardiac arrest in a pediatric patient, comprising administering to the patient an amount of a fibroblast growth factor 21 (FGF21) protein effective to increase RNA binding motif 3 (RBM3) production in the patient. 
     
     
         2 . The method of  claim 1 , further c omprising inducing hypothermia in the patient prior to, during or after administration of the FGF21 protein to the patient. 
     
     
         3 . The method of  claim 2 , wherein the patient's body temperature is maintained at a temperature ranging from 5° C. to 36.5° C. 
     
     
         4 . The method of  claim 2 , wherein the patient's body temperature is reduced and/or maintained at least in part by one or more mechanical cooling devices selected from the group consisting of an ice pack, a fan, a circulating water blanket, a circulating cold air blanket, hydrogel-coated pads, a cooling helmet, a heat-exchange catheter, an extracorporeal heat exchange, intravenous/intravascular infusion of cooled normal saline or lactated Ringer's solution, and heat-exchange by percutaneous indwelling lines. 
     
     
         5 . The method of  claim 2 , wherein the patient's body temperature is reduced and/or maintained at least in part by administering a pharmacologic agent effective to lower a patient's body temperature. 
     
     
         6 . The method of  claim 1 , wherein the FGF21 protein is a human FGF21 protein or a functional FGF21 mutant protein. 
     
     
         7 . The method of  claim 3 , wherein the FGF21 protein is selected from LY2405319, PF-05231023, and an FGF21 protein conjugated to an antibody or a fragment thereof. 
     
     
         8 . The method of  claim 1 , wherein the cardiac arrest is caused by ventricular fibrillation. 
     
     
         9 . The method of  claim 1 , wherein the cardiac arrest is caused by asphyxia. 
     
     
         10 . The method of  claim 1 , wherein the FGF21 protein is delivered by intravenous, oral, intranasal, inhalation, intrathecal, or intracerebroventricular route. 
     
     
         11 . The method of  claim 1 , wherein administration of the FGF21 protein is effective to increase cognition and/or motor function in the patient. 
     
     
         12 . The method of  claim 1 , wherein the FGF21 protein is administered as a bolus, at multiple time points, or as a continuous infusion/release. 
     
     
         13 . The method of  claim 1 , wherein the FGF21 protein is provided in a composition used to infuse a patient to establish and/or maintain hypothermia. 
     
     
         14 . The method of  claim 1 , wherein the FGF21 protein is maintained in the patient in an amount effective to increase RBM3 production in nerve cells of the patient for at least 0.5 hours. 
     
     
         15 . A method of treating cardiac arrest in a pediatric patient, comprising administering to the patient an amount of an FGF21 protein effective to decrease nerve cell injury in the patient. 
     
     
         16 . The method of  claim 15 , further comprising inducing a hypothermic condition prior to, during, or after administering the FGF21 protein to the patient. 
     
     
         17 . The method of  claim 16 , wherein the hypothermic condition maintains the patient at a temperature ranging from 5° C. to 36.5° C. 
     
     
         18 . The method of  claim 16 , wherein which the FGF21 protein is maintained to increase RBM3 production in nerve cells for at least 0.5 hours during the hypothermic condition. 
     
     
         19 . The method of  claim 15 , wherein the FGF21 protein is a human FGF21 protein or a functional FGF21 mutant protein. 
     
     
         20 . The method of  claim 15 , wherein the cardiac arrest is caused by asphyxia or ventricular fibrillation.