Agents, compositions and methods for enhancing neurological function

Abstract

Neuro-enhancing agents, compositions and methods are disclosed herein. Preferred neuro-enhancing agents of the present invention include progesterone and metabolites of progesterone, such as 3α-hydroxy-5α-pregnan-20-one (THP). These agents yield neuro-enhancing effects on neural cells that include neural progenitor and/or stem cells, whereby the agents stimulate mitosis of neural progenitor cells, stimulate neurite growth and organization, protect against neural loss, or one or more of these neural processes. Thus, the neuro-enhancing agents, compositions and methods disclosed herein are useful to reverse or prevent neurological disease or defects associated with neural loss or degeneration, such as Alzheimer's disease, neurological injuries, including injuries resulting from radiation therapy, and age-related neurological decline, including impairments in memory and learning.

1 . A pharmaceutical composition for transdermal administration comprising a compound selected from the group consisting of 3α-hydroxy-5α-pregnan-20-one, a derivative or analog thereof, or a pharmaceutically acceptable salt thereof, and a carrier for transdermal administration. 
   
   
       2 . The composition of  claim 1 , wherein the compound is 3α-hydroxy-5α-pregnan-20-one. 
   
   
       3 . The composition of  claim 2 , wherein the composition is in the form of a gel. 
   
   
       4 . The composition of  claim 3 , wherein the gel comprises a thickening agent. 
   
   
       5 . The composition of  claim 4 , wherein the thickening agent is a cross linked acrylic acid polymer. 
   
   
       6 . The composition of  claim 5 , wherein the crosslinked acrylic acid polymer is carbomer 940. 
   
   
       7 . The composition of  claim 3 , wherein the gel further comprises a solvent. 
   
   
       8 . The composition of  claim 7 , wherein the solvent is selected from the group consisting of diglycol monoethyl ether; ethylene glycol; propylene glycol; dimethyl isosorbide; isopropyl alcohol; and ethanol. 
   
   
       9 . The composition of  claim 8 , wherein the solvent is ethanol. 
   
   
       10 . The composition of  claim 3 , wherein the gel further comprises one or more penetration enhancers. 
   
   
       11 . The composition of  claim 1 , wherein the compound is present in an amount effective to reverse the learning and/or memory deficits in an individual suffering from a neurodegenerative disease, defect, or injury. 
   
   
       12 . The composition of  claim 1 , wherein the compound is present in an amount effective to reduce β-amyloid expression. 
   
   
       13 . The composition of  claim 11  or  12 , wherein the amount of neuro-enhancing agent present in the composition is from about 0.1 to about 1000 mg, preferably from about 0.1 to about 500 mg, more preferably from about 0.1 to about 100 mg. 
   
   
       14 . The composition of  claim 11  or  12 , wherein the concentration of the agent is 10 mg/kg. 
   
   
       15 . A method for reversing the learning and/or memory deficits in an individual suffering from a neurodegenerative disease, defect, or injury the method comprising administering an effective amount of the composition of  claim 1 . 
   
   
       16 . The method of  claim 15 , wherein the composition is administered for a period of at least one month. 
   
   
       17 . The method of  claim 15 , wherein the composition is administered for a period of at least three months. 
   
   
       18 . The method of  claim 15 , wherein the composition is administered for a period of at least six months. 
   
   
       19 . The method of  claim 18 , wherein the composition is administered once a week for a period of six months. 
   
   
       20 . The method of  claim 15 , wherein the amount of 3α-hydroxy-5α-pregnan-20-one or a derivative or analog thereof in the composition is from about 0.1 to about 1000 mg, preferably from about 0.1 to about 500 mg, more preferably from about 0.1 to about 100 mg. 
   
   
       21 . The method of  claim 15  or  19 , wherein the amount of 3α-hydroxy-5α-pregnan-20-one or a derivative or analog thereof is 10 mg/kg. 
   
   
       22 . The method of  claim 15 , wherein the neurodegenerative disease or disorder is Alzheimer's disease. 
   
   
       23 . The method of  claim 15 , wherein the neurodegenerative disease or disorder is Parkinson's disease. 
   
   
       24 . The method of  claim 15 , wherein the neurodegenerative disease or disorder is traumatic brain injury. 
   
   
       25 . A pharmaceutical composition for intranasal administration comprising a compound selected from the group consisting of 3α-hydroxy-5α-pregnan-20-one, a derivative or analog thereof, or a pharmaceutically acceptable salt thereof, and a carrier for intranasal administration. 
   
   
       26 . The composition of  claim 25 , wherein the compound is present in an amount effective to reverse the learning and/or memory deficits in an individual suffering from a neurodegenerative disease, defect, or injury. 
   
   
       27 . The composition of  claim 25 , wherein the compound is present in an amount effective to reduce β-amyloid expression. 
   
   
       28 . A method for reversing the learning and/or memory deficits in an individual suffering from a neurodegenerative disease, defect, or injury the method comprising administering an effective amount of the composition of  claim 25 . 
   
   
       29 . The method of  claim 28 , wherein the composition is administered for a period of at least one month. 
   
   
       30 . The method of  claim 28 , wherein the composition is administered for a period of at least three months. 
   
   
       31 . The method of  claim 28 , wherein the composition is administered for a period of at least six months. 
   
   
       32 . The method of  claim 28 , wherein the composition is administered once a week for a period of six months. 
   
   
       33 . The method of  claim 28 , wherein the neurodegenerative disease or disorder is Alzheimer's disease. 
   
   
       34 . The method of  claim 28 , wherein the neurodegenerative disease or disorder is Parkinson's disease. 
   
   
       35 . The method of  claim 28 , wherein the neurodegenerative disease or disorder is traumatic brain injury.