DNP and DNP Prodrug Treatment of Neuromuscular, Neurodegenerative, Autoimmune, Developmental, Traumatic Brain Injury, Concussion, Dry Eye Disease, Hearing Loss and/or Metabolic Diseases

Abstract

A composition and method of treatment of neuromuscular, neuromuscular degenerative, neurodegenerative, autoimmune, developmental, traumatic, hearing loss related, and/or metabolic diseases, including spinal muscular atrophy (SMA) syndrome (SMA1, SMA2, SMA3, and SMA4, also called Type I, II, III and IV), traumatic brain injury (TBI), concussion, keratoconjunctivitis sicca (Dry Eye Disease), glaucoma, Sjogren's syndrome, rheumatoid arthritis, post-LASIK surgery, anti-depressants use, Wolfram Syndrome, and Wolcott-Rallison syndrome. The composition is selected from the group consisting of 2,3-DNP, 2,4-DNP, 2,5-DNP, 2,6-DNP, 3,4-DNP, or 3,5-DNP, bipartite 2,3-dinitrophenol, 2,4-dinitrophenol, 2,5-dinitrophenol, 2,6-dinitrophenol, 3,4-dinitrophenol, or 3,5-dinitrophenol (2,3-DNP, 2,4-DNP, 2,5-DNP, 2,6-DNP, 3,4-DNP, or 3,5-DNP) prodrugs; Gemini prodrugs, bioprecursor molecules, and combinations thereof. A dose of the composition for treatment of neurodegenerative diseases may be from about 0.01 mg/kg of body weight to about 50 mg/kg of body weight of the patient in need of treatment. A dose of the composition for treatment of metabolic diseases may be from about 1 mg/70 kg of body weight to about 100 mg/70 kg of body weight of the patient in need of treatment, and a maximum dose per day is about 200 mg/70 kg of body weight of the patient in need of treatment.

1 - 46 . (canceled) 
     
     
         47 . A dinitrophenol prodrug of formula I, formula II, formula III, formula IV, formula V, or formula VI: 
       
         
           
           
               
               
           
         
         wherein R is a substituent selected from: 
       
       
         
           
           
               
               
           
         
       
       wherein n is an integer from 1 to 4, R′ is H or alkyl, and X is CH 2 , O, NH, or NR′. 
     
     
         48 . The prodrug of  claim 47 , wherein the prodrug is a compound of formula II. 
     
     
         49 . The prodrug of  claim 47 , wherein R is a substituent selected from: 
       
         
           
           
               
               
           
         
       
     
     
         50 . The prodrug of  claim 47 , wherein R is a substituent selected from: 
       
         
           
           
               
               
           
         
       
     
     
         51 . The prodrug of  claim 47 , wherein R is a substituent selected from: 
       
         
           
           
               
               
           
         
       
     
     
         52 . The prodrug of  claim 47 , wherein R is a substituent selected from: 
       
         
           
           
               
               
           
         
       
     
     
         53 . The prodrug of  claim 47 , wherein the prodrug is stable at a pH of 1-2. 
     
     
         54 . The prodrug of  claim 47 , wherein the prodrug is stable at a pH of 4.5. 
     
     
         55 . The prodrug of  claim 47 , wherein the prodrug is stable at a pH of 5-9. 
     
     
         56 . A “Gemini” dinitrophenol prodrug of Formula VII: 
       
         
           
           
               
               
           
         
       
     
     
         57 . The prodrug of  claim 56 , wherein the prodrug is stable at a pH of 1-2. 
     
     
         58 . The prodrug of  claim 56 , wherein the prodrug is stable at a pH of 4.5. 
     
     
         59 . The prodrug of  claim 56 , wherein the prodrug is stable at a pH of 5-9. 
     
     
         60 . A bioprecursor of 2,3-DNP, 2,4-DNP, 2,5-DNP, 2,6-DNP, 3,4-DNP, or 3,5-DNP, having Formula VIII or Formula IX: 
       
         
           
           
               
               
           
         
       
     
     
         61 . The bioprecursor of  claim 60 , wherein the bioprecursor is stable at a pH of 1-2. 
     
     
         62 . The bioprecursor of  claim 60 , wherein the bioprecursor is stable at a pH of 4.5. 
     
     
         63 . The bioprecursor of  claim 60 , wherein the bioprecursor is stable at a pH of 5-9.