Novel methods of treating a neurodegenerative disease in a mammal in need thereof

Abstract

The present invention provides a method of treating or ameliorating a neurodegenerative disease in a mammal, the method comprising administering to the mammal a therapeutically effective amount of a neurodegenerative disease drug, wherein the drug is a substrate of an ABC transporter inhibitor, wherein the mammal is further administered a therapeutically effective amount of an ARC transporter inhibitor, whereby the neurodegenerative disease is treated in the mammal. In certain embodiments, the neurode generative disease comprises at least one selected from the group consisting of spinal cord injury, Alzheimer's disease, Parkinson's disease, Huntington's disease, prion disease, amyotrophic lateral sclerosis, a tauopathy, and chronic traumatic encephalopathy.

What is claimed is: 
     
         1 . A method of treating or ameliorating a neurodegenerative disease in a mammal in need thereof, the method comprising administering to the mammal a therapeutically effective amount of a neurodegenerative disease drug, wherein the drug is a substrate of an ABC transporter, wherein the mammal is further administered a therapeutically effective amount of an ABC transporter inhibitor, whereby the neurodegenerative disease is treated or ameliorated in the mammal. 
     
     
         2 . The method of  claim 1 , wherein the neurodegenerative disease comprises at least one selected from the group consisting of spinal cord injury, Alzheimer's disease, Parkinson's disease, Huntington's disease, prion disease, amyotrophic lateral sclerosis, a tauopathy, and chronic traumatic encephalopathy. 
     
     
         3 . The method of  claim 1 , wherein the neurodegenerative disease comprises amyotrophic lateral sclerosis. 
     
     
         4 . The method of  claim 1 , wherein the ABC transporter comprises at least one selected from the group consisting of P-gp and BRCP. 
     
     
         5 . The method of  claim 1 , wherein the drug comprises at least one selected from the group consisting of ceftriaxone; celecoxib; ciliary neurotrophic factor; cobalamin; coenzyme Q; gabapentin; HGF; IGF-I; minocycline; N-acetylcysteine; NDGA; pentoxifylline; riluzole; thalidomide; topiramate; valproic acid; VEGF; vitamin E; zVAD-fmk; a salt or solvate thereof, and mixtures thereof. 
     
     
         6 . The method of  claim 1 , wherein the inhibitor comprises at least one selected from the group consisting of elacridar; tariquidar; zosuquidar; ONT-093; laniquidar; a salt or solvate thereof, and mixtures thereof. 
     
     
         7 . The method of  claim 1 , wherein at least one selected from the group consisting of the drug and inhibitor is part of a pharmaceutical composition. 
     
     
         8 . The method of  claim 7 , wherein the pharmaceutical composition comprises an extended-release formulation. 
     
     
         9 . The method of  claim 1 , wherein the drug and the inhibitor are co-administered to the mammal. 
     
     
         10 . The method of  claim 9 , wherein the drug and the inhibitor are coformulated. 
     
     
         11 . The method of  claim 1 , wherein administration of the drug and the inhibitor to the mammal takes place at the time or after the mammal develops at least one symptom of the neurodegenerative disease. 
     
     
         12 . The method of  claim 1 , wherein the mammal that is administered the drug and the inhibitor has a higher spinal cord concentration of the drug than a mammal that is administered the drug only. 
     
     
         13 . The method of  claim 1 , wherein the mammal that is administered the drug and the inhibitor has a higher compound muscle action potential peak amplitude than a mammal that is administered the drug only. 
     
     
         14 . The method of  claim 1 , wherein the mammal that is administered the drug and the inhibitor has improved survival as compared to a mammal that is administered the drug only. 
     
     
         15 . The method of  claim 1 , wherein the mammal that is administered the drug and the inhibitor has delayed disease progression as compared to a mammal that is administered the drug only. 
     
     
         16 . The method of  claim 1 , wherein the mammal is a rodent or a primate. 
     
     
         17 . The method of  claim 16 , wherein the primate is a human. 
     
     
         18 . The method of  claim 1 , wherein the drug is administered to the mammal by at least one route selected from the group consisting of inhalational, oral, rectal, vaginal, parenteral, topical, transdermal, pulmonary, intranasal, buccal, sublingual, ophthalmic, intrathecal, intravenous and intragastrical. 
     
     
         19 . A pharmaceutical composition comprising a neurodegenerative disease drug and an ABC transporter inhibitor, wherein the drug is a substrate of an ABC transporter. 
     
     
         20 . The composition of  claim 19 , wherein the disease comprises at least one selected from the group consisting of spinal cord injury, Alzheimer's disease, Parkinson's disease, Huntington's disease, prion disease, amyotrophic lateral sclerosis, a tauopathy, and chronic traumatic encephalopathy. 
     
     
         21 . The composition of  claim 19 , wherein the disease comprises amyotrophic lateral sclerosis. 
     
     
         22 . The composition of  claim 19 , wherein the ABC transporter comprises at least one selected from the group consisting of P-gp and BRCP. 
     
     
         23 . The composition of  claim 19 , wherein the drug comprises at least one selected from the group consisting of ceftriaxone; celecoxib; ciliary neurotrophic factor; cobalamin; coenzyme Q; gabapentin; HGF; IGF-I; minocycline; N-acetylcysteine; NDGA; pentoxifylline; riluzole; thalidomide; topiramate; valproic acid; VEGF; vitamin E; zVAD-fmk; a salt or solvate thereof, and mixtures thereof. 
     
     
         24 . The composition of  claim 19 , wherein the inhibitor comprises at least one selected from the group consisting of elacridar; tariquidar; zosuquidar; ONT-093; laniquidar; a salt or solvate thereof, and mixtures thereof. 
     
     
         25 . The composition of  claim 19 , wherein the composition is formulated for inhalational, oral, rectal, vaginal, parenteral, topical, transdermal, pulmonary, intranasal, buccal, sublingual, ophthalmic, intrathecal, intravenous or intragastrical administration.