Treatment of Central Nervous System Disorders

Abstract

The invention relates generally to methods of influencing central nervous system cells to produce progeny useful in the treatment of CNS disorders. More specifically, the invention includes methods of exposing a patient suffering from such a disorder to a reagent that modulates the proliferation, migration, differentiation and survival of central nervous system cells. These methods are useful for reducing at least one symptom of the disorder.

1 . A method of alleviating a symptom of a disease or disorder of the nervous system in a patient in need thereof comprising administering VEGF to a neural tissue of said patient in an a therapeutically effective amount sufficient to induce the proliferation or differentiation of, or modulate the survival of, a neural stem cell or neural progenitor cell located in said neural tissue. 
     
     
         2 . The method of  claim 1 , wherein the VEGF is administered in an amount of 0.001 ng/kg/day to 10 mg/kg/day, 
     
     
         3 . The method of  claim 1 , wherein the VEGF is administered in an amount of 0.01 ng/kg/day to 5 mg/kg/day, 
     
     
         4 . The method of  claim 1 , wherein the VEGF is administered in an amount of 0.1 ng/kg/day to 1 mg/kg/day, 
     
     
         5 . The method of  claim 1 , wherein the VEGF is administered in an amount of 0.1 ng/kg/day to 1 ug/kg/day. 
     
     
         6 . The method of  claim 1 , wherein the VEGF is administered by injection, administered to the buccal, nasal or rectal mucosa, or administered via peptide fusion or micelle delivery. 
     
     
         7 . The method of  claim 6 , wherein the injection is given subcutaneously, intraperitoneally, intramusclularly, intracerebroventricularly, intraparenchymally, intrathecally or intracranially. 
     
     
         8 . The method of  claim 1 , wherein the disease or disorder of the nervous system is selected from the group consisting of neurodegenerative disorders, neural stem cell disorders, neural progenitor disorders, ischemic disorders, neurological traumas, affective disorders, neuropsychiatric disorders, learning and memory disorders, Parkinson's disease and Parkinsonian disorders, Huntington's disease, Alzheimer's disease, Amyotrophic Lateral Sclerosis, spinal ischemia, ischemic stroke, spinal cord injury, cancer-related brain/spinal cord injury, schizophrenia and other psychoses, depression, bipolar depression/disorder, anxiety syndromes/disorders, phobias, stress and related syndromes, cognitive function disorders, aggression, drug and alcohol abuse, obsessive compulsive behaviour syndromes, seasonal mood disorder, borderline personality disorder, cerebral palsy, life style drug, multi-infarct dementia, Lewy body dementia, age related/geriatric dementia, epilepsy and injury related to epilepsy, spinal cord injury, brain injury, trauma related brain/spinal cord injury, anti-cancer treatment related brain/spinal cord tissue injury, infection and inflammation related brain/spinal cord injury, environmental toxin related brain/spinal cord injury, multiple sclerosis, autism, attention deficit disorders, nacrolepsy and sleep disorders. 
     
     
         9 . The method of  claim 1 , wherein the VEGF is VEGF-A, VEGF-B, VEGF-C, VEGF-D, a VEGF agonist, or a combination thereof. 
     
     
         10 . The method of  claim 9 , wherein the VEGF-A is VEGF-A 165  or VEGF-A 121 . 
     
     
         11 . The method of  claim 1 , further comprising administering a ventricle wall permeability enhancer. 
     
     
         12 . The method of  claim 11 , wherein the ventricle wall permeability enhancer is administered before, during, or after administration of the VEGF. 
     
     
         13 . The method of  claim 11 , wherein the ventricle wall permeability enhancer and the VEGF or VEGF agonist are admixed with a pharmaceutically acceptable carrier. 
     
     
         14 . The method of  claim 1 , further comprising administering one or more agents selected from the group consisting of stem cell mitogens, survival factors, glial- lineage preventing agents, anti-apoptotic agents, anti-stress medications, neuroprotectants, anti-pyrogenics, and a combination thereof.