Use of SCF and G-CSF in the treatment of cerebral ischemia and neurological disorders

Abstract

The present invention relates to the use of stem cell factor (SCF) polypeptide, alone and in combination with granulocyte colony stimulating factor (G-CSF) polypeptide, in the prevention or treatment of injury to the brain after cerebral ischemia or neurological disorder. More particularly, the invention provides methods of improving neurological function and outcome after stroke by the administration of SCF polypeptide, alone and in combination with G-CSF polypeptide. This treatment can be used alone or in combination with other well-known methods of treatment of cerebral ischemia and neurological disorders in a mammal.

1 . A method of improving neurological function and outcome in a mammal suffering from cerebral ischemia, comprising administering an effective amount of a composition comprising stem cell factor (SCF) polypeptide, alone or in combination with granulocyte colony stimulating factor (G-CSF) polypeptide.  
   
   
       2 . A method of improving neurological function and outcome in a mammal suffering from cerebral ischemia, comprising administering an effective amount of a composition comprising granulocyte colony stimulating factor (G-CSF) polypeptide, alone or in combination with stem cell factor (SCF) polypeptide.  
   
   
       3 - 4 . (canceled)  
   
   
       5 . The method of claims  1  or  2 , wherein the composition includes at least one additional agent.  
   
   
       6 . The method of  claim 5 , wherein the additional agent is selected from the group consisting of: a growth factor, a thrombolytic agent, or a neurotrophic factor, such as brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), glial cell line-derived neurotrophic factor (GDNF), basic fibroblastic growth factor (bFGF), epidermal growth factor (EGF), platelet-derived growth factor (PDGF), and insulin-like growth factor (IGF).  
   
   
       7 . The method of claims  1  or  2 , wherein the improvement in neurological function is characterized by improved sensorimotor skills and coordination.  
   
   
       8 . The method of claims  1  or  2 , wherein the improvement in neurological function is characterized by improved brain plasticity.  
   
   
       9 . The method of claims  1  or  2 , wherein the improvement in neurological function is characterized by increased neural progenitor cell proliferation and differentiation.  
   
   
       10 . The method of claims  1  or  2 , wherein the improvement in neurological function is characterized by increased neuronal cell signaling.  
   
   
       11 . The method of claims  1  or  2 , wherein the improvement in neurological function is characterized by increased neuronal survival.  
   
   
       12 . The method of claims  1  or  2 , wherein the improvement in neurological function is characterized by decreased neuronal apoptosis.  
   
   
       13 . The method of claims  1  or  2 , wherein the improvement in neurological function is characterized by decreased neuronal toxicity.  
   
   
       14 . The method of claims  1  or  2 , wherein the improvement in neurological function is characterized by reduced infarct volume or decreased total tissue loss.  
   
   
       15 . The method of claims  1  or  2 , wherein said mammal is a human.  
   
   
       16 . The method of claims  1  or  2 , wherein the composition is administered during the chronic stage of stroke.  
   
   
       17 . The method of claims  1  or  2 , wherein the composition is administered during the acute stage of stroke.  
   
   
       18 . A kit containing components for treating cerebral ischemia comprised of: 
 a.) a composition comprising SCF polypeptide;    b.) a composition comprising G-CSF polypeptide; and    c.) optionally, at least one additional factor selected from the group consisting of: a growth factor, thrombolytic agent, or neurotrophic factor, such as brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), glial cell line-derived neurotrophic factor (GDNF), basic fibroblastic growth factor (bFGF), epidermal growth factor (EGF), platelet-derived growth factor (PDGF), and insulin-like growth factor (IGF).    
   
   
       19 . A method of improving neurological function and outcome in a mammal suffering from a neurological disorder, comprising administering an effective amount of a composition comprising stem cell factor (SCF) polypeptide, alone or in combination with granulocyte colony stimulating factor (G-CSF) polypeptide.  
   
   
       20 . A method of improving neurological function and outcome in a mammal suffering from a neurological disorder, comprising administering an effective amount of a composition comprising granulocyte colony stimulating factor (G-CSF) polypeptide, alone or in combination with stem cell factor (SCF) polypeptide.  
   
   
       21 - 36 . (canceled)  
   
   
       37 . The method of claims  19  or  20 , wherein the neurological disorder is selected from the group consisting of: Alzheimer's Disease (AD), Parkinson's Disease (PD), Huntington's Disease (HD), motor neuron disease, amyotrophic lateral sclerosis (ALS), cerebral palsy, genetic syndromes, epilepsy, spinal cord injury, neurodevelopmental malformations, brain dysplasias, and other less common neurodegenerative disorders.  
   
   
       38 . A kit containing components for treating a neurological disorder comprised of: 
 a.) a composition comprising SCF polypeptide;    b.) a composition comprising G-CSF polypeptide; and    c.) optionally, at least one additional factor selected from the group consisting of: a growth factor, thrombolytic agent, or neurotrophic factor, such as brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), glial cell line-derived neurotrophic factor (GDNF), basic fibroblastic growth factor (bFGF), epidermal growth factor (EGF), platelet-derived growth factor (PDGF), and insulin-like growth factor (IGF).