Treating neural disease with tyrosine kinase inhibitors

Abstract

Provided herein are methods of treating or preventing a neurodegenerative disease, a myodegenerative disease or a prion disease in a subject comprising administering a tyrosine kinase inhibitor.

1 .- 31 . (canceled) 
     
     
         31 . A method of treating Alzheimer's disease in a subject in need thereof, comprising:
 selecting a subject with Alzheimer's disease or at risk for Alzheimer's disease; and   administering to the subject an effective amount of a tyrosine kinase inhibitor, wherein the tyrosine kinase inhibitor is not Gleevec, and wherein the tyrosine kinase inhibitor crosses the blood brain barrier.   
     
     
         32 . The method of  claim 31 , wherein the tyrosine kinase inhibitor is selected from the group consisting of nilotinib, bosutinib and a combination thereof. 
     
     
         33 . The method of  claim 31 , wherein the effective amount of the tyrosine kinase inhibitor is less than about 10 mg/kg. 
     
     
         34 . The method of  claim 31 , wherein the tyrosine kinase inhibitor is administered daily. 
     
     
         35 . The method of  claim 31 , further comprising administering a second therapeutic agent to the subject. 
     
     
         36 . A method of inhibiting or preventing toxic protein aggregation in a neuron of a subject with Alzheimers's disease, comprising contacting the neuron in the subject with an effective amount of a tyrosine kinase inhibitor, wherein the tyrosine kinase inhibitor is not Gleevec, and wherein the tyrosine kinase inhibitor crosses the blood brain barrier. 
     
     
         37 . The method of  claim 36 , wherein the tyrosine kinase inhibitor is selected from the group consisting of nilotinib, bosutinib and a combination thereof. 
     
     
         38 . The method of  claim 36 , wherein the protein is selected from the group consisting of amyloid-β and tau protein. 
     
     
         39 . The method of  claim 36 , wherein the effective amount of the tyrosine kinase inhibitor is less than about 10 mg/kg. 
     
     
         40 . A method of treating Lewy Body disease in a subject in need thereof, comprising:
 selecting a subject with Lewy Body disease or at risk for Lewy Body disease; and   administering to the subject an effective amount of a tyrosine kinase inhibitor, wherein the tyrosine kinase inhibitor is not Gleevec, and wherein the tyrosine kinase inhibitor crosses the blood brain barrier.   
     
     
         41 . The method of  claim 40 , wherein the tyrosine kinase inhibitor is selected from the group consisting of nilotinib, bosutinib and a combination thereof. 
     
     
         42 . The method of  claim 40 , wherein the effective amount of the tyrosine kinase inhibitor is less than about 10 mg/kg. 
     
     
         43 . The method of  claim 40 , wherein the tyrosine kinase inhibitor is administered daily. 
     
     
         44 . The method of  claim 40 , further comprising administering a second therapeutic agent to the subject. 
     
     
         45 . A method of inhibiting or preventing toxic protein aggregation in a neuron of a subject with Lewy Body disease, comprising contacting the neuron in the subject with an effective amount of a tyrosine kinase inhibitor, wherein the tyrosine kinase inhibitor is not Gleevec, and wherein the tyrosine kinase inhibitor crosses the blood brain barrier. 
     
     
         46 . The method of  claim 45 , wherein the tyrosine kinase inhibitor is selected from the group consisting of nilotinib, bosutinib and a combination thereof. 
     
     
         47 . The method of  claim 45 , wherein the protein is selected from the group consisting of alpha-synuclein and insoluble Parkin. 
     
     
         48 . The method of  claim 45 , wherein the effective amount of the tyrosine kinase inhibitor is less than about 10 mg/kg. 
     
     
         49 . A method of treating Parkinson's disease in a subject in need thereof, comprising:
 selecting a subject with Parkinson's disease or at risk for Parkinson's disease; and   administering to the subject an effective amount of a tyrosine kinase inhibitor, wherein the tyrosine kinase inhibitor is not Gleevec, and wherein the tyrosine kinase inhibitor crosses the blood brain barrier.   
     
     
         50 . The method of  claim 49 , wherein the tyrosine kinase inhibitor is selected from the group consisting of nilotinib, bosutinib and a combination thereof. 
     
     
         51 . The method of  claim 49 , wherein the effective amount of the tyrosine kinase inhibitor is less than about 10 mg/kg. 
     
     
         52 . The method of  claim 49 , wherein the tyrosine kinase inhibitor is administered daily. 
     
     
         53 . The method of  claim 49 , further comprising administering a second therapeutic agent to the subject. 
     
     
         54 . A method of inhibiting or preventing toxic protein aggregation in a neuron of a subject with Parkinson's disease, comprising contacting the neuron in the subject with an effective amount of a tyrosine kinase inhibitor, wherein the tyrosine kinase inhibitor is not Gleevec, and wherein the tyrosine kinase inhibitor crosses the blood brain barrier. 
     
     
         55 . The method of  claim 54 , wherein the tyrosine kinase inhibitor is selected from the group consisting of nilotinib, bosutinib and a combination thereof. 
     
     
         56 . The method of  claim 54 , wherein the protein is selected from the group consisting of alpha-synuclein and insoluble Parkin. 
     
     
         57 . The method of  claim 54 , wherein the effective amount of the tyrosine kinase inhibitor is less than about 10 mg/kg.