Methods and kit for treating parkinson's disease

Abstract

The efficacy of levodopa therapy in patients being treated for Parkinson's disease is enhanced by administering high doses of a partial glycine agonist. The frequency and severity of levodopa-induced side effects in Parkinson's disease patients are also reduced by administration of a partial glycine agonist.

1 - 42 . (canceled)  
   
   
       43 . A therapeutic combination comprising levodopa in an amount effective to treat Parkinson's disease in a subject, and a partial glycine agonist in an amount effective to enhance efficacy of the levodopa or to reduce frequency or severity of side effects of the levodopa in the subject.  
   
   
       44 . The combination of  claim 43 , further comprising a peripheral dopa decarboxylase inhibitor.  
   
   
       45 . The combination of  claim 44 , wherein the peripheral dopa decarboxylase inhibitor comprises carbidopa or benserazide.  
   
   
       46 . The combination of  claim 43 , wherein the partial glycine agonist comprises D-cycloserine or 1-aminocyclopropanecarboxylic acid.  
   
   
       47 . The combination of  claim 43 , wherein the amount of the partial glycine agonist is an amount per dose sufficient to deliver greater than 1 mg of partial glycine agonist per kg body weight of the subject.  
   
   
       48 . The combination of  claim 43 , wherein the partial glycine agonist is D-cycloserine and is present in an amount per dose sufficient to deliver greater than 1 mg to 12 mg of D-cycloserine per kg body weight of the subject.  
   
   
       49 . The combination of  claim 43 , wherein the amount of the partial glycine agonist is sufficient to produce a concentration thereof in the brain of the subject at which antagonism of the glycine binding site of the NMDA receptor occurs.  
   
   
       50 . The combination of  claim 43 , wherein the levodopa and glycine partial agonist are present in a single pharmaceutical composition.  
   
   
       51 . The combination of  claim 50 , wherein the single composition further comprises a peripheral dopa decarboxylase inhibitor.  
   
   
       52 . The combination of  claim 43 , wherein the levodopa and partial glycine agonist are present in separate pharmaceutical compositions.  
   
   
       53 . The combination of  claim 43 , wherein at least one of the levodopa and the partial glycine agonist is present in a form adapted for parenteral administration.  
   
   
       54 . The combination of  claim 43 , wherein at least one of the levodopa and glycine partial agonist is present in a form adapted for enteral administration.  
   
   
       55 . The combination of  claim 54 , wherein the levodopa and the glycine partial agonist are each present in a form adapted for oral administration.  
   
   
       56 . A pharmaceutical composition comprising (a) levodopa in an amount effective to treat Parkinson's disease in a subject, (b) a partial glycine agonist in an amount effective to enhance efficacy of the levodopa or to reduce frequency or severity of side effects of the levodopa in the subject, and (c) one or more pharmaceutically acceptable excipients.  
   
   
       57 . The composition of  claim 56 , further comprising a peripheral dopa decaboxylase inhibitor.  
   
   
       58 . The composition of  claim 57 , wherein the peripheral dopa decarboxylase inhibitor comprises carbidopa or benserazide.  
   
   
       59 . The composition of  claim 56 , wherein the partial glycine agonist comprises D-cycloserine or 1-aminocyclopropanecarboxylic acid.  
   
   
       60 . The composition of  claim 56 , wherein the amount of the partial glycine agonist is sufficient to deliver, per dose, greater than 1 mg of partial glycine agonist per kg body weight of the subject.  
   
   
       61 . The composition of  claim 56 , wherein the partial glycine agonist is D-cycloserine and is present in an amount sufficient to deliver, per dose, greater than 1 mg to 12 mg of D-cycloserine per kg body weight of the subject.  
   
   
       62 . The composition of  claim 56 , wherein the amount of the partial glycine agonist is sufficient to produce a concentration thereof in the brain of the subject at which antagonism of the glycine binding site of the NMDA receptor occurs.  
   
   
       63 . The composition of  claim 56 , that is in a form adapted for parenteral administration.  
   
   
       64 . The composition of  claim 56 , that is in a form adapted for enteral administration.  
   
   
       65 . The composition of  claim 64 , that is in a form adapted for oral administration.  
   
   
       66 . The composition of  claim 56 , that is in a form selected from the group consisting of aqueous and oily suspensions, tablets, dispersible powders and granules, emulsions, hard and soft capsules, syrups, elixirs, suppositories, liposome preparations, microencapsulated preparations, transdermal patches and sprays.  
   
   
       67 . The composition of  claim 56 , wherein the one or more excipients comprise at least one excipient selected from the group consisting of water, saline, suspending agents, dispersing agents, sweetening agents, flavoring agents, coloring agents, preserving agents, wetting agents, condensation agents, inert diluents, binding agents, lubricating agents, and combinations thereof.  
   
   
       68 . A method for treating Parkinson's disease in a subject, comprising administering levodopa and a partial glycine agonist to the subject, wherein the partial glycine agonist is administered in an amount effective to enhance efficacy of the levodopa or to reduce frequency or severity of side effects of the levodopa.  
   
   
       69 . The method of  claim 68 , further comprising administering a peripheral dopa decaboxylase inhibitor to the subject.  
   
   
       70 . The method of  claim 69 , wherein the peripheral dopa decarboxylase inhibitor comprises carbidopa or benserazide.  
   
   
       71 . The method of  claim 68 , wherein the partial glycine agonist comprises D-cycloserine or 1-aminocyclopropanecarboxylic acid.  
   
   
       72 . The method of  claim 68 , wherein the partial glycine agonist is administered in an amount per dose sufficient to deliver greater than 1 mg of partial glycine agonist per kg body weight of the subject.  
   
   
       73 . The method of  claim 68 , wherein the partial glycine agonist is D-cycloserine and is administered in an amount per dose sufficient to deliver greater than 1 mg to 12 mg of D-cycloserine per kg body weight of the subject.  
   
   
       74 . The method of  claim 68 , wherein the partial glycine agonist is administered in an amount sufficient to produce a concentration thereof in the brain of the subject at which antagonism of the glycine binding site of the NMDA receptor occurs.  
   
   
       75 . The method of  claim 68 , wherein the levodopa and the partial glycine agonist are administered in a single pharmaceutical composition.  
   
   
       76 . The method of  claim 75 , wherein the single composition further comprises a peripheral dopa decarboxylase inhibitor.  
   
   
       77 . The method of  claim 68 , wherein the levodopa and partial glycine agonist are administered in separate pharmaceutical compositions.  
   
   
       78 . The method of  claim 68 , wherein at least one of the levodopa and the partial glycine agonist is administered parenterally.  
   
   
       79 . The method of  claim 68 , wherein at least one of the levodopa and the partial glycine agonist is administered enterally.  
   
   
       80 . The method of  claim 79 , wherein the levodopa and the partial glycine agonist are each administered orally.  
   
   
       81 . The method of  claim 68 , wherein the frequency or severity is reduced of one or more levodopa side effects selected from the group consisting of dyskinesias, dystonias, deterioration of daily function, depression, anxiety, cognitive disorders and combinations thereof.  
   
   
       82 . The method of  claim 68 , wherein the subject is selected from the group consisting of primates and rodents.  
   
   
       83 . The method of  claim 68 , wherein the subject is human.