Use of low-dose ladostigil for neuroprotection

Abstract

The subject invention provides a method of preventing a neurodegenerative disease in a subject or oxidative stress in the brain of a subject, comprising administering to the subject a less than cholinesterase-inhibitory amount or a less than monoamine oxidase-inhibitory amount of R(+)-6-(N-methyl,N-ethyl-carbamoyloxy)-N′-propargyl-1-aminoindan or a salt thereof effective to prevent the neurodegenerative disease or oxidative stress in the subject.

What is claimed is: 
     
         1 . A method of preventing the appearance of symptoms of a neurodegenerative disease in a subject predisposed to the neurodegenerative disease, comprising administering to the subject an amount of R(+)-6-(N-methyl,N-ethyl-carbamoyloxy)-N′-propargyl-1-aminoindan or a salt thereof effective to prevent the appearance of symptoms of the disease that causes no more than 30% monoamine oxidase (MAO) inhibition or no more than 30% acetylcholine esterase (ChE) inhibition. 
     
     
         2 . The method of  claim 1 , comprising administering to the subject a less than cholinesterase-inhibitory amount and a less than monoamine oxidase-inhibitory amount of R (+)-6-(N-methyl, N-ethyl-carbamoyloxy)-N′-propargyl-1-aminoindan or a salt thereof. 
     
     
         3 . The method of  claim 1 , comprising administration of a salt of R(+)-6-(N-methyl, N-ethyl-carbamoyloxy)-N′ -propargyl-1-aminoindan. 
     
     
         4 . The method of  claim 3 , wherein the salt of R(+)-6-(N-methyl,N-ethyl-carbamoyloxy)-N′-propargyl-1-aminoindan is the tartrate salt. 
     
     
         5 . The method of  claim 1 , wherein the subject is a human. 
     
     
         6 . The method of  claim 5 , wherein the amount of R(+)-6-(N-methyl,N-ethyl-carbamoyloxy)-N′-propargyl-1-aminoindan is no more than 0.37 mg/kg/day of the subject, or a corresponding amount of the salt thereof. 
     
     
         7 . The method of  claim 6 , wherein the salt is the tartrate salt and the corresponding amount of the salt is no more than 0.46 mg/kg/day of the subject. 
     
     
         8 . The method of  claim 5 , wherein the amount of R(+)-6-(N-methyl,N-ethyl-carbamoyloxy)-N′-propargyl-1-aminoindan or a salt thereof administered is 10 mg/day-25 mg/day. 
     
     
         9 . The method of  claim 5 , wherein the amount of R(+)-6-(N-methyl,N-ethyl-carbamoyloxy)-N′-propargyl-1-aminoindan or a salt thereof administered is 0.14 mg/kg/day-0.42 mg/kg/day of the subject. 
     
     
         10 . The method of  claim 9 , wherein the amount of R(+)-6-(N-methyl,N-ethyl-carbamoyloxy)-N′-propargyl-1-aminoindan or a salt thereof administered is 0.15 mg/kg/day of the subject. 
     
     
         11 . The method of  claim 1 , further comprising administering to the subject an antioxidant. 
     
     
         12 . The method of  claim 1 , wherein the neurodegenerative disease is Alzheimer's disease, dementia, Parkinson's disease, age-related macular degeneration, or amyotrophic lateral sclerosis. 
     
     
         13 . The method of  claim 1 , wherein the disease is dementia and the dementia is static dementia, senile dementia, presenile dementia, progressive dementia, vascular dementia or Lewy body dementia. 
     
     
         14 . The method of  claim 1  for reducing oxidative stress in the brain of a subject afflicted with oxidative stress. 
     
     
         15 . The method of  claim 14 , wherein the oxidative stress occurs in the hippocampus region of the brain. 
     
     
         16 . The method of  claim 15 , wherein the oxidative stress occurs in the astrocytes of the hippocampus region of the brain.