Inhibition of DUX4 Expression Using Bromodomain and Extra-Terminal Domain Protein Inhibitors (BETi)

Abstract

The use of BETi as a potential treatment for FSHD is provided. Specifically, the use of BETi, and particularly selective BETi for BRD4, are shown to inhibit DUX4 expression which is expected to result in a decrease in the severity of symptoms of FSHD. Further, the treatments are shown to work when pulsed as opposed to continuous. This allows for a BETi to be supplied to a human in a pulse, and then allows the human to not need any additional treatment for a window at least as long as the one of the treatment pulse.

1 . A method of reducing muscular weakness from facioscapulohumeral muscular dystrophy (FSHD), the method comprising:
 administering to a patient with FHSD a therapeutic quantity of a BET inhibitor (BETi) sufficient to reduce DUX4 expression in said patient.   
     
     
         2 . The method of  claim 1 , wherein said BETi is selected from the group consisting of: (+)-JQ1, PFI-1, I-BET-762, I-BET-151, RVX-208, and CPI-0610. 
     
     
         3 . The method of  claim 1  wherein said BETi is a selective inhibitor of BRD2. 
     
     
         4 . The method of  claim 1  wherein said BETi is a selective inhibitor of BRD4. 
     
     
         5 . The method of  claim 1  wherein said BETi is a broad spectrum inhibitor. 
     
     
         6 . The method of  claim 1  wherein in said administering, said BETi is provided in an initial dose and a second dose is not provided for at least 24 hours after said initial dose is finished. 
     
     
         7 . The method of  claim 6  wherein said initial dose is provided continuously over 24 hours. 
     
     
         8 . The method of  claim 6  wherein in said administering, said BETi is provided in an initial dose and a second dose is not provided for at least 48 hours after said initial dose is finished. 
     
     
         9 . The method of  claim 6  wherein in said administering, said BETi is provided in an initial dose and a second dose is not provided for at least 72 hours after said initial dose is finished. 
     
     
         10 . The method of  claim 6  wherein in said administering, said BETi is provided in an initial dose and a second dose is not provided for at least 96 hours after said initial dose is finished. 
     
     
         11 . The method of  claim 1 , wherein said patient is human.