Inhibition of DUX4 expression using bromodomain and extra-terminal domain protein inhibitors (BETi)
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 FSHD 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.
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.
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.
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.
11. The method of claim 1 , wherein said patient is human.