US2001051602A1PendingUtilityA1

Methods for increasing ApoE levels for the treatment of neurodegenerative disease

Priority: Sep 24, 1997Filed: Jun 22, 2001Published: Dec 13, 2001
Est. expirySep 24, 2017(expired)· nominal 20-yr term from priority
Inventors:Judes Poirier
A61P 25/28A61P 25/00A61P 25/02A61P 25/16A61P 25/14A61K 31/366A61P 21/00A61K 45/06A61K 31/10A61K 31/407
43
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Claims

Abstract

Disclosed herein is a method for reducing neurodegenerative disease in patients by administration of a therapeutically-effective amount of a compound which can increase ApoE levels.

Claims

exact text as granted — not AI-modified
What is claimed is:  
     
         1 . A method of treating a neuronal deficit in a patient, said patient diagnosed with a neurodegenerative disease or a predisposition to a neurodegenerative disease, said method comprising administering a therapeutically-effective amount of a composition other than tacrine, donepezil, or estrogen, said composition being a composition which increases ApoE levels.  
     
     
         2 . The method of    claim 1   , wherein, said neurodegenerative disease is a disease other than AD.  
     
     
         3 . The method of    claim 1   , wherein said neurodegenerative disease is a disease other than stroke.  
     
     
         4 . The method of    claim 1   , wherein said composition comprises a compound selected from the group comprising probucol, heptylphysostigmine, simvastatin, lovastatin, pravastatin, and thorvastatin.  
     
     
         5 . A method of treating a neuronal deficit in a patient, said patient diagnosed with a non-Alzheimer's neurodegenerative disease or a predisposition to a non-Alzheimer's neurodegenerative disease, said method comprising administering a therapeutically effective amount of a composition which increases ApoE levels.  
     
     
         6 . The method of    claim 5   , wherein said composition comprises a compound selected from the group comprising probucol, tacrine, heptylphysostigmine, simvastatin, lovastatin, pravastatin, thorvastatin, and steroids.  
     
     
         7 . The method of    claim 5   , wherein said composition comprises estrogen.  
     
     
         8 . The method of    claim 1   , wherein said method includes administering a second compound, said second compound selected from the group comprising probucol analogs, vitamin E, donepezil, blood pressure inhibitors, antioxidants, anti-inflammatories, or steroids other than estrogen.  
     
     
         9 . The method of    claim 5   , wherein said method includes administering a second compound, said second compound selected from the group comprising probucol analogs, tacrine, vitamin E, donepezil, blood pressure inhibitors, antioxidants, anti-inflammatories, or steroids.  
     
     
         10 . The method of claims  1  or  5 , wherein said amount of a composition is sufficient to increase ApoE levels in said patient.  
     
     
         11 . The method of    claim 10   , wherein said amount of a composition is sufficient to increase ApoE levels by about 10% or more.  
     
     
         12 . The method of claims  1  or  5 , wherein said amount of a composition is sufficient to increase amyloid scavenging by ApoE.  
     
     
         13 . The method of claims  1  or  5 , wherein said patient has a disease of the central nervous system.  
     
     
         14 . The method of claims  1  or  5 , wherein said patient has a disease of the peripheral nervous system.  
     
     
         15 . The method of claims  1  or  5 , wherein said patient is presymptomatic.  
     
     
         16 . The method of claims  1  or  5 , wherein said patient has at least one apoE4 allele.  
     
     
         17 . The method of claims  1  or  5 , wherein said patient has been diagnosed to suffer from, Creutzfeldt-Jakob disease, Huntington's disease, Lewy body disease, Parkinson's disease, Pick's disease, amyotrophic lateral sclerosis, neurofibromatosis, brain injury, stroke, multiple sclerosis, or multiple infarct dementia.  
     
     
         18 . The method of    claim 1   , wherein said patient has been diagnosed to suffer from Alzheimer's disease.  
     
     
         19 . The method of claims  1  or  5 , wherein said patient is genetically predisposed to suffer from a disease selected from the group consisting of Creutzfeldt-Jakob disease, Huntington's disease, Lewy body disease, Parkinson's disease, Pick's disease, amyotrophic lateral sclerosis, multiple sclerosis, stroke, multiple infarct dementia, and neurofibromatosis.  
     
     
         20 . The method of    claim 1   , wherein said patient is genetically predisposed to suffer from Alzheimer's disease.  
     
     
         21 . The method of    claim 1   , wherein said administering further includes administering tacrine to said patient.  
     
     
         22 . The method of    claim 1   , wherein said administering further includes administering estrogen to said patient.  
     
     
         23 . The method of    claim 1   , wherein said administering further includes administering donepezil to said patient.  
     
     
         24 . A method of increasing ApoE polypeptide levels in a patient, said method comprising administering a therapeutically-effective amount of a composition comprising probucol or an analog of probucol.  
     
     
         25 . The method of    claim 24   , wherein said patient has a neurodegenerative disease.  
     
     
         26 . The method of    claim 24   , wherein said patient has a disease of the central nervous system.  
     
     
         27 . The method of    claim 24   , wherein said patient has a disease of the peripheral nervous system.  
     
     
         28 . The method of    claim 24   , wherein said patient is suffering from Alzheimer's disease.  
     
     
         29 . The method of    claim 24   , wherein said patient is genetically predisposed to suffer from Alzheimer's disease.  
     
     
         30 . The method of    claim 24   , wherein said patient has at least one apoE4 allele.  
     
     
         31 . The method of    claim 24   , wherein said patient is suffering from Creutzfeldt-Jakob disease, Huntington's disease, Lewy body disease, Parkinson's disease, Pick's disease, amyotrophic lateral sclerosis, neurofibromatosis, brain injury, stroke, multiple sclerosis, or multiple infarct dementia.  
     
     
         32 . The method of    claim 24   , wherein said patient is genetically predisposed to suffer from a disease selected from the group consisting of Creutzfeldt-Jakob disease, Huntington's disease, Lewy body disease, Parkinson's disease, Pick's disease, amyotrophic lateral sclerosis, multiple sclerosis, stroke, multiple infarct dementia, and neurofibromatosis.  
     
     
         33 . The method of    claim 24   , wherein said therapeutically effective amount of a composition may comprise a compound selected from the group comprising probucol analogs, tacrine, heptylphysostigmine, simvastatin, lovastatin, pravastatin, thorvastatin, vitamin E, donepezil, blood pressure inhibitors, antioxidants, anti-inflammatories, and steroids.  
     
     
         34 . The method of    claim 24   , wherein said composition further includes one or more compounds selected from the group comprising, vitamin E, donepezil, blood pressure inhibitors, antioxidants, anti-inflammatories, and steroids.  
     
     
         35 . The method of    claim 24   , wherein said expression is measured by quantitating ApoE polypeptide levels.  
     
     
         36 . The method of    claim 24   , wherein said expression is measured by quantitating ApoE polypeptide levels with an antibody.  
     
     
         37 . The method of    claim 24   , wherein said increasing is in brain tissue or human cerebrospinal fluid of said patient.  
     
     
         38 . A method of identifying a therapeutic compound effective for the treatment of a neurodegenerative disease, said method comprising exposing a cell to a compound and measuring the expression of ApoE, an increase in said expression identifying a therapeutic compound.  
     
     
         39 . The method of    claim 38   , wherein an increase ApoE levels by 10% or more indicates a therapeutic compound.  
     
     
         40 . The method of    claim 38   , wherein said cell is an astrocyte, neuron, glial cell, oligodendrocyte, Schwann cell or any other cell derived from nervous system tissue.  
     
     
         41 . The method of    claim 38   , wherein said cell is derived from nervous system tissue from a patient with, or predicted to suffer from, a neurodegenerative disease.  
     
     
         42 . The method of    claim 38   , wherein said expression is measured by quantitating apoE mRNA levels.  
     
     
         43 . The method of    claim 38   , wherein said expression is measured by quantitating ApoE polypeptide levels.

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