Novel pharmacological therapy for neuronopathic gaucher disease

Abstract

The instant disclosure relates to methods and compositions for the treatment of Gaucher disease, particularly type II and III neuronopathic Gaucher disease (nGD). The methods include the step of administering to an individual in need thereof an effective amount of a ryanodine receptor inhibitor or a pharmaceutically acceptable salt thereof.

1 . A method of treating a condition associated with neuronopathic Gaucher disease (nGD), in an individual in need thereof, comprising administering an effective amount of dantrolene or pharmaceutically acceptable salt thereof to said individual wherein said condition is selected from one or more of brain inflammation, neuron loss, and neurodegeneration. 
     
     
         2 . The method of  claim 1 , wherein said Gaucher disease is type II. 
     
     
         3 . The method of  claim 1 , wherein said Gaucher disease is type III. 
     
     
         4 - 13 . (canceled) 
     
     
         14 . A method for a neurological sign in an individual having nGD, comprising administering dantrolene, or pharmaceutically salt thereof, to said individual. 
     
     
         15 . The method of  claim 1 , wherein said improvement in neurodegeneration is an improvement in gait impairment. 
     
     
         16 . The method of  claim 1 , wherein said administration is in an amount sufficient to increase GCase activity. 
     
     
         17 . The method of  claim 1 , wherein said administration reduces substrate accumulation. 
     
     
         18 . The method of  claim 1 , wherein said administration protects calmodulin and CAMKIV expression.