Dosing regimens of pkc activators

Abstract

Dosing regimens and methods are disclosed for upregulating on protein kinase C (PKC) while reducing subsequent downregulation, comprising administering a PKC activator once a week for three consecutive weeks followed by cessation of administration or dosing for three consecutive weeks. Also described are methods for improving or enhancing cognitive ability, preventing or treating cognitive impairment, preventing or treating a neurodegenerative disease or condition, and/or preventing or treating a disease or condition associated with neuronal or synaptic loss according to the disclosed regimens.

What is claimed is: 
     
         1 . A dosing regimen for improving or enhancing a cognitive ability of a subject comprising:
 administering to the subject a therapeutically effective amount of a PKC activator once a week for three consecutive weeks, followed by cessation of dosing for three consecutive weeks.   
     
     
         2 . The dosing regimen according to  claim 1 , wherein the subject is in need of treatment for a neurodegenerative disorder. 
     
     
         3 . The dosing regimen according to  claim 2 , wherein the neurodegenerative disorder is chosen from Alzheimer's disease, chronic traumatic encephalopathy (CTE), Parkinson's disease, multiple sclerosis, traumatic brain injury, Fragile X, Niemann-Pick C, frontotemporal dementia, vascular dementia, depression, bipolar disorder, schizophrenia, Post-Traumatic Stress Disorder, stroke, mental retardation, or brain injury. 
     
     
         4 . The dosing regimen according to  claim 3 , wherein the neurodegenerative disorder is Alzheimer's disease. 
     
     
         5 . The dosing regimen according to  claim 1 , wherein the PKC activator is chosen from macrocyclic lactones, bryologs, diacylglcerols, isoprenoids, octylindolactam, gnidimacrin, ingenol, iripallidal, napthalenesulfonamides, diacylglycerol inhibitors, growth factors, polyunsaturated fatty acids, monounsaturated fatty acids, cyclopropanated polyunsaturated fatty acids, cyclopropanated monounsaturated fatty acids, fatty acids alcohols and derivatives, and fatty acid esters. 
     
     
         6 . The dosing regimen according to  claim 5 , wherein the macrocyclic lactone is bryostatin. 
     
     
         7 . The dosing regimen according to  claim 6 , wherein the bryostatin is chosen from bryostatin-1, bryostatin-2, bryostatin-3, bryostatin-4, bryostatin-5, bryostatin-6, bryostatin-7, bryostatin-8, bryostatin-9, bryostatin-10, bryostatin-11, bryostatin-12, bryostatin-13, bryostatin-14, bryostatin-15, bryostatin-16, bryostatin-17, or bryostatin-18. 
     
     
         8 . The dosing regimen according to  claim 6 , wherein the therapeutically effective amount of the PKC activator is about 25 μg/m 2 . 
     
     
         9 . A method for improving or enhancing a cognitive ability of a subject comprising:
 administering to the subject a therapeutically effective amount of a PKC activator once a week for three consecutive weeks, followed by cessation of dosing for three consecutive weeks.   
     
     
         10 . The method according to  claim 9 , wherein the subject is in need of treatment for a neurodegenerative disorder. 
     
     
         11 . The method according to  claim 10 , wherein the neurodegenerative disorder is chosen from Alzheimer's disease, chronic traumatic encephalopathy (CTE), Parkinson's disease, multiple sclerosis, traumatic brain injury, Fragile X, Niemann-Pick C, frontotemporal dementia, vascular dementia, depression, bipolar disorder, schizophrenia, Post-Traumatic Stress Disorder, stroke, mental retardation, or brain injury. 
     
     
         12 . The method according to  claim 11 , wherein the neurodegenerative disorder is Alzheimer's disease. 
     
     
         13 . The method according to  claim 9 , wherein the PKC activator is chosen from macrocyclic lactones, bryologs, diacylglcerols, isoprenoids, octylindolactam, gnidimacrin, ingenol, iripallidal, napthalenesulfonamides, diacylglycerol inhibitors, growth factors, polyunsaturated fatty acids, monounsaturated fatty acids, cyclopropanated polyunsaturated fatty acids, cyclopropanated monounsaturated fatty acids, fatty acids alcohols and derivatives, and fatty acid esters. 
     
     
         14 . The method according to  claim 13 , wherein the macrocyclic lactone is bryostatin. 
     
     
         15 . The method according to  claim 14 , wherein the bryostatin is chosen from bryostatin-1, bryostatin-2, bryostatin-3, bryostatin-4, bryostatin-5, bryostatin-6, bryostatin-7, bryostatin-8, bryostatin-9, bryostatin-10, bryostatin-11, bryostatin-12, bryostatin-13, bryostatin-14, bryostatin-15, bryostatin-16, bryostatin-17, or bryostatin-18. 
     
     
         16 . The method according to  claim 15 , wherein the therapeutically effective amount of the PKC activator is about 25 μg/m 2 .