US2003060436A1PendingUtilityA1

Treatment of parkinson's disease with oligonucleotides

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Assignee: CLIFFORD KENT WEBER ESQPriority: Nov 5, 1998Filed: Nov 5, 1999Published: Mar 27, 2003
Est. expiryNov 5, 2018(expired)· nominal 20-yr term from priority
Inventors:Jay Schneider
A61K 31/711C12N 2310/152A61K 38/00C12N 15/1137A61P 25/16C12N 2310/315
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Claims

Abstract

The present invention relates to a method of treatment of Parkinson's disease, and to the use of antisense oligonucleotides or triplex oligonucleotides introduced into targeted brain structures to decrease the function of brain circuits known to be overactive in the Parkinsonian brain. Antisense or triplex oligonucleotides are targeted to the internal globus pallidus and/or substantia nigra pars reticulata (SNr) where the expression of glutamic acid decarboxylase (GAD 67 , GAD 65 , or a combination of the two isoforms) is downregulated. The present invention also relates to a method of treatment of Parkinson's disease where antisense or triplex oligonucleotides are targeted to the internal globus pallidus and/or substantia nigra pars reticulata for the downregulation of glutamate receptors. The present invention further relates to a method of treatment of Parkinson's disease where antisense or triplex oligonucleotides are targeted to the thatlamic motor nuclei for the downregulation of GABA receptors.

Claims

exact text as granted — not AI-modified
What is claimed is:  
     
         1 . A method of treating Parkinson's disease in a mammal, comprising administering a therapeutically effective amount of antisense oligonucleotide to the substantia nigra pars reticulata for the downregulation of glutamic acid decarboxylase.  
     
     
         2 . The method of  claim 1  wherein the isoform of said glutamic acid decarboxylase is GAD 65 .  
     
     
         3 . The method of  claim 1  wherein the isoform of said glutamic acid decarboxylase is GAD 67 .  
     
     
         4 . The method of  claim 1  where in the isoform of said glutamic acid decarboxylase is a combination of GAD 65  and GAD 67 .  
     
     
         5 . A method of treating Parkinson's disease in a mammal, comprising administering a therapeutically effective amount of triplex oligonucleotide to the substantia nigra pars reticulata for the downregulation of glutamic acid decarboxylase.  
     
     
         6 . The method of  claim 5  wherein the isoform of said glutamic acid decarboxylase is GAD 65 .  
     
     
         7 . The method of  claim 5  wherein the isoform of said glutamic acid decarboxylase is GAD 67 .  
     
     
         8 . The method of  claim 5  wherein the isoform of said glutamic acid decarboxylase is GAD 65  and GAD 67 .  
     
     
         9 . A method of treating Parkinson's disease in a mammal, comprising administering a therapeutically effective amount of antisense oligonucleotide to the internal globus pallidus for the downregulation of glutamic acid decarboxylase.  
     
     
         10 . The method of  claim 9  wherein said isoform of said glutamic acid decarboxylase GAD 65 .  
     
     
         11 . The method of  claim 9  wherein the isoform of said glutamic acid decarboxylase is GAD 67 .  
     
     
         12 . The method of  claim 9  wherein the isoform of said glutamic acid decarboxylase is GAD 65  and GAD 67 .  
     
     
         13 . A method of treating Parkinson's disease in a mammal, comprising administering a therapeutically effective amount of triplex oligonucleotide to the internal globus pallidus for the downregulation of glutamic acid decarboxylase.  
     
     
         14 . The method of  claim 13  wherein the isoform of said glutamic acid decarboxylase is GAD 65 .  
     
     
         15 . The method of  claim 13  wherein the isoform of said glutamic acid decarboxylase is GAD 67 .  
     
     
         16 . The method of  claim 13  wherein the isoform of said glutamic acid decarboxylase is GAD 65  and GAD 67 .  
     
     
         17 . A method of treating Parkinson's disease in a mammal, comprising administering a therapeutically effective amount of antisense oligonucleotide to the substantia nigra pars reticulata for the downregulation of glutamate receptors.  
     
     
         18 . A method of treating Parkinson's disease in a mammal, comprising administering a therapeutically effective amount of triplex oligonucleotide to the substantia nigra pars reticulata for the downregulation of glutamate receptors.  
     
     
         19 . A method of treating Parkinson's disease in a mammal, comprising administering a therapeutically effective amount of antisense oligonucleotide to the internal globus pallidus for the downregulation of glutamate receptors.  
     
     
         20 . A method of treating Parkinson's disease in a mammal, comprising administering a therapeutically effective amount of triplex oligonucleotide to the internal globus pallidus for the downregulation of glutamate receptors.  
     
     
         21 . A method of treating Parkinson's disease in a mammal, comprising administering a therapeutically effective amount of antisense oligonucleotide to the thanlamic motor nuclei for the downregulation of GABA receptors.  
     
     
         22 . A method of treating Parkinson's disease in a mammal, comprising administering a therapeutically effective amount of triplex oligonucleotide to the thanlamic motor nuclei for the downregulation of GABA receptors.

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