Compositions and methods for treating fibrotic disease
The present disclosure relates to compositions and methods for treating or preventing a fibrotic disorder or disease.
1. A method for treating or ameliorating a fibrotic disease, comprising administering to a subject having the fibrotic disease a therapeutically effective amount of a modulator specific for eIF4A, eIF4E, or both, thereby treating or ameliorating the fibrotic disease, wherein the fibrotic disease is idiopathic pulmonary fibrosis.
2. The method according to claim 1 , wherein the modulator is administered after a fibrotic lesion has developed in the subject.
3. The method according to claim 1 , wherein the modulator is formulated with a pharmaceutically acceptable excipient.
4. The method according to claim 1 , wherein the modulator is administered in combination with one or more adjunctive therapeutic agents.
5. The method according to claim 4 , wherein the one or more adjunctive therapeutic agents is selected from angiotensin converting enzyme inhibitor, nintedanib, STX-100, QAX576, CNTO-888, SD-208, SB-525334, GC1008, BMS-986202, AM152, lebrikizumab, tralokinumab, SAR156597, PRM-151, simtuzumab (AB0024, GS-6624), GSK2126458, FG-3019, captopril, genistein, silvestrol or derivatives thereof, pirfenidone, pateamine A or derivatives thereof, hippuristanol, or EUK-207.
6. The method according to claim 1 , wherein the subject is a human.
7. The method of claim 1 , wherein the modulator specific for eIF4A or eIF4E is selected from the group consisting of silvestrol, an siRNA or a derivative thereof, and any combinations thereof.
8. The method of claim 4 , wherein (a) the modulator comprises a modulator of eIF4A and the adjunctive therapeutic agent comprises a modulator of EIF2AK1, (b) the modulator comprises a modulator of eIF4A and the adjunctive therapeutic agent comprises a modulator of deoxyhypusine synthase (DHPS), or (c) the modulator comprises a modulator of eIF4A and the adjunctive therapeutic agent comprises a modulator of deoxyhypusine hydroxylase (DOHH).
9. The method of claim 4 , wherein (a) the modulator comprises a modulator of eIF4E and the adjunctive therapeutic agent comprises a modulator of EIF2AK1, (b) the modulator comprises a modulator of eIF4E and the adjunctive therapeutic agent comprises a modulator of deoxyhypusine synthase (DHPS), or (c) the modulator comprises a modulator of eIF4E and the adjunctive therapeutic agent comprises a modulator of deoxyhypusine hydroxylase (DOHH).