Inhibitors of glucosylceramide degradation in the treatment of diseases of the motor units

Abstract

Inhibitors of glucosylceramide degradation, to pharmaceutical compositions containing same, and to the use of same in the treatment of diseases of the motor units, such as amyotrophic lateral sclerosis.

1 . An inhibitor of glucosylceramide degradation or a pharmaceutical acceptable salt thereof, for use in a method for the treatment of diseases of the motor units. 
     
     
         2 . The inhibitor of glucosylceramide degradation or a pharmaceutical acceptable salt thereof according to  claim 1 , wherein the inhibitor of glucosylceramide degradation or a pharmaceutical acceptable salt thereof inhibits the activity of glucocerebrosidase (GBA) or the activity of β-glucosidase 2 (GBA2) or at least one enzyme responsible for GCase activity. 
     
     
         3 . The inhibitor of glucosylceramide degradation or a pharmaceutical acceptable salt thereof according to  claim 1 , wherein the inhibitor of glucosylceramide degradation is isofagomin, miglustat, NB-DNJ, NB-DGJ, AMP-DNM, cyclophellitol, β-thiirane, cyclophellitol aziridine, ambroxol, GENZ-642347, celastrol, eliglustat, GENZ-667161, conduritol B epoxide or a pharmaceutically acceptable salt thereof. 
     
     
         4 . The inhibitor of glucosylceramide degradation according to  claim 1 , wherein the inhibitor of glucosylceramide degradation is Conduritol B epoxide or ambroxol, or a pharmaceutically acceptable salt thereof. 
     
     
         5 . The inhibitor of glucosylceramide degradation according to  claim 1 , wherein the diseases of the motor units are selected among the group of Amyotrophic Lateral Sclerosis, Spinal-Bulbar Muscular Atrophy, Primary Lateral Sclerosis, Guillain-Barré Syndrom, Spinal Muscular Atrophy and disorders of the motor units resulting from an accident. 
     
     
         6 . A pharmaceutical composition comprising at least an inhibitor of glucosylceramide degradation or a pharmaceutically acceptable salt thereof according to  claim 1  as an active ingredient and at least one pharmaceutically acceptable carrier for use in a method for the treatment of diseases of the motor units. 
     
     
         7 . The pharmaceutical composition according to  claim 6 , wherein the diseases of the motor units are selected among the group of Amyotrophic Lateral Sclerosis, Spinal-Bulbar Muscular Atrophy, Primary Lateral Sclerosis, Guillain-Barré Syndrom, Spinal Muscular Atrophy and disorders of the motor units resulting from an accident. 
     
     
         8 . The pharmaceutical composition comprising the inhibitor of glucosylceramide degradation or a pharmaceutically acceptable salt thereof according to  claim 6 , wherein the pharmaceutical composition is administered to the patient with disease of the motor unit at a dose of 0.01 to 500 mg/kg of body weight/day. 
     
     
         9 . The pharmaceutical composition comprising the inhibitor of glucosylceramide degradation or a pharmaceutically acceptable salt thereof according to  claim 8 , wherein the pharmaceutical composition is administered to the patient with disease of the motor unit at a dose of 0.1 to 250 mg/kg of body weight/day.