Methods of treating cognitive impairment

Abstract

The subject invention concerns materials and methods for treating a person or animal having cognitive impairment. In one embodiment, the method comprises administering an effective amount of one or more inflammatory mediator(s), for example, fms-related tyrosine kinase 3 (Flt3) ligand, interleukin-6 (IL-6), macrophage migration inhibitory factor (MIF), interleukin-1 (IL-1), interleukin-3 (IL-3), erythropoietin (EPO), vascular endothelial growth factor A (VEGF-A), hypoxia-inducible transcription factor (HIF-1alpha), insulin like growth factor-1 (IGF-1), tumor necrosis factor (TNF), granulocyte colony-stimulating factor (G-CSF), granulocyte/macrophage colony-stimulating factor (GM-CSF), macrophage colony-stimulating factor (M-CSF), Stem Cell Factor (SCF), Darbepoetin (ARANESP), and metalloproteinases, to an animal or person in need of treatment.

We claim: 
     
         1 . A method for treating cognitive impairment in a person or animal comprising administering to the person or animal an effective amount of one or more inflammatory mediator(s), or a functional fragment or variant thereof that exhibits substantially the same biological activity as the full-length or non-variant inflammatory mediator, or a polynucleotide encoding said inflammatory mediator, or a compound or agent that induces production of said inflammatory mediator, wherein said inflammatory mediator is able to cross the blood brain barrier. 
     
     
         2 . The method of  claim 1 , wherein said inflammatory mediator comprises one or more of a fms-related tyrosine kinase 3 (Flt3) ligand, interleukin-6 (IL-6), macrophage migration inhibitory factor (MIF), interleukin-1 (IL-1), interleukin-3 (IL-3), erythropoietin (EPO), vascular endothelial growth factor A (VEGF-A), hypoxia-inducible transcription factor (HIF-1alpha), insulin like growth factor-1 (IGF-1), tumor necrosis factor (TNF), granulocyte colony-stimulating factor (G-CSF), granulocyte/macrophage colony-stimulating factor (GM-CSF), Stem Cell Factor (SCF), Darbepoetin (ARANESP), or a metalloproteinase, or a functional fragment or variant thereof that exhibits substantially the same biological activity as the full-length or non-variant inflammatory mediator. 
     
     
         3 . The method of  claim 1 , wherein said inflammatory mediator comprises GM-CSF, or a functional fragment or variant thereof that exhibits substantially the same biological activity as the full-length or non-variant GM-CSF. 
     
     
         4 . The method of  claim 1 , wherein said inflammatory mediator comprises a biological equivalent of GM-CSF. 
     
     
         5 . The method of  claim 1 , wherein said inflammatory mediator is capable of reducing amyloid beta levels in the plasma or brain of the treated person or animal. 
     
     
         6 . The method of  claim 3 , wherein said GM-CSF is capable of reducing neural tangles in the plasma or brain of the treated person or animal. 
     
     
         7 . The method of  claim 1 , wherein the cognitive impairment is caused by or results from Alzheimer's disease. 
     
     
         8 . The method of  claim 1 , wherein the inflammatory mediator is administered intracranially. 
     
     
         9 . The method of  claim 1 , wherein the inflammatory mediator is administered by intracranial infusion. 
     
     
         10 . The method of  claim 1 , wherein the inflammatory mediator is administered to a non-neural cell or tissue. 
     
     
         11 . The method of  claim 1 , wherein said method further comprises evaluating the person or animal for cognitive impairment prior to treatment. 
     
     
         12 . The method of  claim 1 , wherein said composition comprises a pharmaceutically acceptable carrier, diluent, or solute. 
     
     
         13 . The method of  claim 1 , wherein said polynucleotide is provided in an expression construct. 
     
     
         14 . The method of  claim 13 , wherein said expression construct provides for expression of said polynucleotide in neural cells. 
     
     
         15 . The method of  claim 14 , wherein said neural cells are human cells. 
     
     
         16 . The method of  claim 1 , wherein said compound or agent that induces production of said inflammatory mediator is EPO or HIF-1α. 
     
     
         17 . The method of  claim 1 , wherein said cognitive impairment is caused by or results from stroke, Down's syndrome, dementia pugilistica, traumatic brain injury, AIDS-associated dementia, Lewy body disease, or Pick's disease. 
     
     
         18 . The method of  claim 1 , wherein i) G-CSF and/or GM-CSF and ii) Darbepoetin and/or EPO are administered to the person or animal.