Compositions for treating cmt and related disorders

Abstract

The present invention relates to compositions and methods for the treatment of the Charcot-Marie-Tooth disease and related disorders.

We claim: 
     
         1 . A method of treating Charcot-Marie-Tooth disease or a related disorder comprising administering to a subject suffering from Charcot-Marie-Tooth disease or a related disorder an effective amount of at least baclofen, sorbitol and a compound selected from pilocarpine, methimazole, mifepristone, naltrexone, rapamycin, flurbiprofen, or ketoprofen, or salts, enantiomers, racemates or prodrugs thereof. 
     
     
         2 . The method of  claim 1 , which comprises administering at least baclofen, D-sorbitol and naltrexone, or salts, enantiomers, racemates or prodrugs thereof. 
     
     
         3 . The method of  claim 1 , wherein the compounds are formulated with a pharmaceutically suitable excipient or carrier. 
     
     
         4 . The method of  claim 1 , wherein the compounds are formulated or administered together or separately. 
     
     
         5 . The method of  claim 1 , wherein the compounds are formulated with a drug eluting polymer, a biomolecule, a micelle or liposome-forming lipids or oil in water emulsions, or pegylated or solid nanoparticles or microparticles for oral or parenteral or intrathecal administration. 
     
     
         6 . The method of  claim 1 , for treating CMT1A. 
     
     
         7 . The method of  claim 1 , wherein said related disorder is amyotrophic lateral sclerosis. 
     
     
         8 . The method of  claim 1 , wherein said related disorder is a neuropathy. 
     
     
         9 . The method of  claim 8 , wherein the neuropathy is selected from idiopathic neuropathies, diabetic neuropathy, toxic neuropathies, neuropathies induced by drug treatments, neuropathies provoked by HIV, neuropathies provoked by radiation, neuropathies provoked by heavy metals, neuropathies provoked by vitamin deficiency states, or traumatic neuropathies. 
     
     
         10 . The method of  claim 9 , wherein the traumatic neuropathies are selected from traumatic brain injury, spinal cord injury, or peripheral nerves injuries. 
     
     
         11 . A method for treating a traumatic neuropathy according to  claim 10 , comprising administering to a subject in need thereof baclofen, D-sorbitol and naltrexone, or salts, enantiomers, racemates or prodrugs thereof. 
     
     
         12 . A method for treating CMT1A according to  claim 6 , comprising administering to a subject in need thereof baclofen, D-sorbitol and naltrexone, or salts, enantiomers, racemates or prodrugs thereof. 
     
     
         13 . A method of improving nerve regeneration in a subject in need thereof, said method comprising administering to said subject an effective amount of a composition comprising baclofen, sorbitol and a compound selected from pilocarpine, methimazole, mifepristone, naltrexone, rapamycin, flurbiprofen, or ketoprofen, or salts, enantiomers, racemates or prodrugs thereof. 
     
     
         14 . The method of  claim 13 , wherein the composition comprises naltrexone, baclofen and D-sorbitol or salts, enantiomers, racemates or prodrugs thereof. 
     
     
         15 . The method of  claim 13 , wherein the composition further comprises a pharmaceutically suitable excipient or carrier. 
     
     
         16 . The method of  claim 13 , wherein the compounds of the composition are formulated with a drug eluting polymer, a biomolecule, a micelle or liposome-forming lipids or oil in water emulsions, or pegylated or solid nanoparticles or microparticles for oral or parenteral or intrathecal administration. 
     
     
         17 . The method of  claim 13 , wherein improving nerve regeneration comprises improving or accelerating recovery from a neuronal insult. 
     
     
         18 . The method of  claim 13 , wherein improving nerve regeneration comprises improving nerve myelination or restoring, at least partially, axon morphology or electrophysiological functions. 
     
     
         19 . The method of  claim 17 , wherein said neuronal insult is of genetic origin. 
     
     
         20 . The method of  claim 17 , wherein the neuronal insult is of chemical origin. 
     
     
         21 . The method of  claim 17 , wherein the neuronal insult is traumatic. 
     
     
         22 . The method of  claim 13 , wherein said subject is suffering from Charcot-Marie-Tooth disease or a related disorder. 
     
     
         23 . The method of  claim 22 , wherein said related disorder is amyotrophic lateral sclerosis or a neuropathy selected from idiopathic neuropathies, diabetic neuropathy, toxic neuropathies, neuropathies induced by drug treatments, neuropathies provoked by HIV, neuropathies provoked by radiation, neuropathies provoked by heavy metals, neuropathies provoked by vitamin deficiency states, or traumatic neuropathies. 
     
     
         24 . The method of  claim 23 , wherein the traumatic neuropathies are selected from traumatic brain injury, spinal cord injury, or peripheral nerves injuries.