Methods of treating neurological conditions with hematopoeitic growth factors

Abstract

The present invention relates to a method of treating a neurological condition in a mammal by administering at least one hematopoietic growth factor.

1 . A method of treating a neurological condition in a mammal, comprising administering to the mammal in need thereof, a hematopoietic factor selected from the group consisting of GCSF, GMCSF, IL-3, IL-5, a derivative thereof, a mimetic thereof, and a combination thereof in an amount sufficient to treat the neurological condition. 
     
     
         2 . The method of  claim 1 , wherein said neurological condition is selected from the group consisting of a neurological disease with pathophysiological mechanisms involving ischemia, a neurological disease with pathophysiological mechanisms involving hypoxia, a neurodegenerative disease, and a disease of the nervous system accompanied by neural cell death. 
     
     
         3 . The method of  claim 1 , wherein the neurological condition is neurological disease with pathophysiological mechanisms involving ischemia or hypoxia. 
     
     
         4 . The method of  claim 3 , wherein the neurological disease with pathophysiological mechanisms involving ischemia or hypoxia is stroke. 
     
     
         5 . The method of  claim 1 , further comprising administering one or more additional hematopoietic factors. 
     
     
         6 . The method of  claim 1 , wherein the neurological condition is a psychiatric condition. 
     
     
         7 . The method of  claim 6 , wherein the psychiatric condition is depression. 
     
     
         8 . The method of  claim 1 , wherein the neurological condition is a dementia or multiple sclerosis. 
     
     
         9 . The method of  claim 5 , wherein the hematopoietic factors are selected from the group consisting of G-CSF, GM-CSF, derivatives thereof, mimetics thereof, combinations thereof and wherein the additional hematopoietic factor is erythropoietin. 
     
     
         10 . The method of  claim 5 , wherein a combination comprising at least two hematopoietic factors selected from the group consisting of GCSF, GMCSF, IL-3, IL-5, a derivative thereof, and a mimetic thereof and wherein the additional hematopoietic factor is erythropoietin. 
     
     
         11 . The method of  claim 1 , wherein the neurological condition is stroke, Parkinson's disease, amyotrophic lateral sclerosis, neurotrauma, cerebral ischemia due to cardiac arrest, cerebral ischemia during an operative procedure, multiple sclerosis, Huntington's disease, glaucoma, neuropathy, a lysosomal storage disease, or spinal cord injury. 
     
     
         12 . The method of  claim 1 , wherein the hematopoietic factor is IL-3, a derivative thereof, a mimetic thereof, or a combination thereof. 
     
     
         13 . The method of  claim 1 , wherein the hematopoietic factor is IL-5, a derivative thereof, a mimetic thereof or a combination thereof. 
     
     
         14 . The method of  claim 1 , which further comprises administering a hemodynamically active compound. 
     
     
         15 . The method of  claim 1 , which further comprises administering tissue plasminogen activator to the mammal. 
     
     
         16 . The method of  claim 1 , which further comprises administering an agent that facilitates passage over the blood brain barrier. 
     
     
         17 . The method of  claim 1 , which further comprises administering an anti-apoptotic agent. 
     
     
         18 . The method of  claim 15 , wherein the neurological condition is stroke. 
     
     
         19 . The method of  claim 10 , further comprising administering tissue plasminogen activator to the mammal. 
     
     
         20 . The method of  claim 1 , wherein the hematopoietic factor is a human factor or derived from a human factor. 
     
     
         21 . The method of  claim 1 , wherein the mammal is human. 
     
     
         22 . The method of  claim 1 , wherein the hematopoietic factor is administered by one or more modes of administration selected from the group consisting of direct intracerebral injection, intravenously, intraarterially, orally, and subcutaneously. 
     
     
         23 . The method of  claim 1 , wherein the administering of the hematopoietic factor comprises administering a polynucleotide, which when administered in the mammal expresses the hematopoietic factor in an amount sufficient to treat the neurological condition. 
     
     
         24 . The method of  claim 23 , wherein the polynucleotide is administered with a viral vector or a liposome. 
     
     
         25 . A method of treating a neurological condition in a mammal in need thereof, comprising contacting a neural stem cell composition with a hematopoietic factor selected from the group consisting of GCSF, GMCSF, IL-3, IL-5, a derivative thereof, a mimetic thereof, and a combination thereof; and subsequently administering the neural stem cells to the mammal. 
     
     
         26 . The method of  claim 25 , wherein said neurological condition is selected from the group consisting of a neurological disease with pathophysiological mechanisms involving ischemia, a neurological disease with pathophysiological mechanisms involving hypoxia, a neurodegenerative disease, and a disease of the nervous system accompanied by neural cell death. 
     
     
         27 . The method of  claim 26 , a neurological disease with pathophysiological mechanisms involving ischemia or hypoxia. 
     
     
         28 . The method of  claim 27  wherein the neurological disease with pathophysiological mechanisms involving ischemia or hypoxia is stroke. 
     
     
         29 . The method of  claim 25 , wherein the neurological condition is a psychiatric condition. 
     
     
         30 . The method of  claim 29 , wherein the psychiatric condition is depression. 
     
     
         31 . The method of  claim 25 , wherein the neurological condition is a dementia or multiple sclerosis. 
     
     
         32 . The method of  claim 25 , further comprising contacting the neural stem cell composition with one or more additional hematopoietic factors. 
     
     
         33 . The method of  claim 32 , wherein the hematopoietic factors are selected from the group consisting of GCSF, GMCSF, and derivatives thereof, mimetics thereof, and combinations thereof, and wherein the additional hematopoietic factors is erythropoietin. 
     
     
         34 . The method of  claim 33 , wherein the neural stem cell composition is contacted with a combination of at least two hematopoietic factors selected from the group consisting of GCSF, GMCSF, IL-3, IL-5, a derivative thereof, and a mimetic thereof; and erythropoietin. 
     
     
         35 . The method of  claim 25 , wherein the neurological condition is stroke, Parkinson's disease, amyotrophic lateral sclerosis, neurotrauma, cerebral ischemia due to cardiac arrest, cerebral ischemia during an operative procedure, multiple sclerosis, Huntington's disease, glaucoma, neuropathy, a lysosomal storage disease, or spinal cord injury. 
     
     
         36 . The method of  claim 25 , wherein the hematopoietic factor is IL-3, a derivative thereof, a mimetic thereof, or a combination thereof. 
     
     
         37 . The method of  claim 25 , wherein the hematopoietic factor is IL-5, a derivative thereof, a mimetic thereof, or a combination thereof. 
     
     
         38 . The method of  claim 25 , wherein the hematopoietic factor is a human factor or derived from a human factor. 
     
     
         39 . The method of  claim 25 , wherein the mammal is human. 
     
     
         40 . The method of  claim 25 , wherein the neural stem cell composition comprises human neural stem cells. 
     
     
         41 . A method of enhancing the survival of a cell transplanted into a mammal, comprising introducing into the cell one or more polynucleotides which encode a hematopoietic factor selected from the group consisting of IL-3, IL-5, a derivative thereof, a mimetic thereof, and a combination thereof, wherein the cell expresses the hematopoietic factor in an amount sufficient to enhance the survival of the cell relative to the cell survival prior to introducing the one or more polynucleotides. 
     
     
         42 . The method of  claim 41 , wherein the cell further expresses and secretes one or more additional hematopoietic factors. 
     
     
         43 . The method of  claim 42 , wherein the additional hematopoietic factors are selected from the group consisting of GCSF, GMCSF, erythropoietin, derivatives thereof, mimetics thereof, and combinations thereof. 
     
     
         44 . The method of  claim 41 , wherein the hematopoietic factor is IL-3, a derivative thereof, a mimetic thereof, or a combination thereof. 
     
     
         45 . The method of  claim 41 , wherein the hematopoietic factor is IL-5, a derivative thereof, a mimetic thereof, or a combination thereof. 
     
     
         46 . The method of  claim 41 , wherein the mammal is human. 
     
     
         47 . The method of  claim 41 , wherein the cell is a neural cell. 
     
     
         48 . The method of  claim 47 , wherein the neural cell is a neural stem cell. 
     
     
         49 . The method of  claim 47 , wherein the cell is a stem cell. 
     
     
         50 . The method of  claim 41 , wherein the cell further expresses one or both of an IL-3 receptor and an IL-5 receptor. 
     
     
         51 . The method of  claim 41 , wherein the cell is transplanted into neural tissue of the mammal. 
     
     
         52 . A method of enhancing the viability of a neural cell culture comprising contacting the neural cell culture with a hematopoietic factor selected from the group consisting of IL-3, IL-5, a derivative thereof, a mimetic thereof, and a combination thereof in an amount sufficient to enhance the viability of the neural cell culture relative to the culture prior to contacting with the hematopoietic factor. 
     
     
         53 . The method of  claim 52 , wherein the neural cell culture comprises neural stem cells. 
     
     
         54 . A method of enhancing the viability of a neural cell culture comprising introducing one or more polynucleotides into the cells of the neural cell culture wherein the polynucleotide is expresses a hematopoietic factor selected from the group consisting of IL-3, IL-5, a derivative thereof, a mimetic thereof, and a combination thereof, and wherein the polynucleotide expresses the hematopoietic factor in an amount sufficient to enhance the viability of the neural cell culture relative to the culture prior to contacting with the hematopoietic factor. 
     
     
         55 . The method of  claim 54 , wherein the polynucleotide is administered with a viral vector or a liposome. 
     
     
         56 . A method for enhancing the cognitive ability of a mammal in need thereof, comprising administering a hematopoietic factor selected from the group consisting of IL-3, IL-5, a derivative thereof, a mimetic thereof, and a combination thereof in an amount sufficient to enhance the cognitive ability of a mammal relative to the mammal prior to the administrating. 
     
     
         57 . The method of  claim 56 , wherein the mammal is a human.