Methods and compositions to treat drug-induced diseases and conditions

Abstract

Methods and compounds useful to treat drug-induced diseases and conditions are provided. Methods of administering one or more MCJ-inhibiting compounds to decrease MCJ polypeptide activity in cells, tissues, and/or subjects as a treatment for a drug-induced disease or condition are provided.

What is claimed is: 
     
         1 . A method for treating a drug-induced liver injury (DILI) in a subject, the method comprising administering to a subject in need of such treatment an MCJ-modulating compound in an amount effective to treat the DILI in the subject, wherein the MCJ-inhibiting compound comprises an MCJ small interference RNA molecule (MCJ siRNA) or an MCJ small hairpin RNA molecule (MCJ shRNA) that reduces MCJ polypeptide activity in the subject, wherein decreasing the MCJ polypeptide activity comprises decreasing one or more of an MCJ polypeptide level or activity. 
     
     
         2 - 4 . (canceled) 
     
     
         5 . The method of  claim 1 , wherein the DILI is an acute condition. 
     
     
         6 - 7 . (canceled) 
     
     
         8 . The method of  claim 1 , wherein the MCJ-modulating compound further comprises a targeting agent, optionally a mitochondrial targeting agent. 
     
     
         9 - 10 . (canceled) 
     
     
         11 . The method of claim  10 , wherein the siRNA molecule comprises a nucleic acid sequence set forth herein as SEQ ID NO:21. 
     
     
         12 . The method of claim  10 , wherein the siRNA molecule comprises a nucleic acid sequence set forth herein as SEQ ID NO: 7. 
     
     
         13 . The method of  claim 1 , wherein the MCJ-modulating compound is administered in a pharmaceutical composition, and wherein the pharmaceutical composition further comprises a pharmaceutically acceptable carrier and optionally comprises one or more of a carrier agent, a delivery agent, a labeling agent, and a targeting agent. 
     
     
         14 . The method of  claim 13 , wherein the carrier agent comprises one or more of a nanocarrier, a cell-penetrating peptide, a polymer, a dendrimer, an siRNA bioconjugate, and a lipid-based siRNA carrier. 
     
     
         15 . The method of  claim 13 , wherein the pharmaceutical composition additionally comprises a drug known to or suspected of inducing the DILI. 
     
     
         16 - 23 . (canceled) 
     
     
         24 . The method of  claim 1 , wherein the MCJ-modulating compound is administered to the subject at one or more of before, concurrently with, and after ingestion by the subject of a drug suitable to induce the DILI. 
     
     
         25 . A method of reducing a drug-induced liver injury (DILI) in a cell, the method comprising contacting the cell with an MCJ-inhibiting compound in an amount effective to decrease an MCJ polypeptide activity in the cell, wherein the MCJ-inhibiting compound comprises an MCJ small interference RNA molecule (MCJ siRNA) or an MCJ small hairpin RNA molecule (MCJ shRNA) that decreases one or more of an MCJ polypeptide level or function of an MCJ polypeptide in the liver cell. 
     
     
         26 - 32 . (canceled) 
     
     
         33 . The method of  claim 25 , wherein the siRNA molecule comprises a nucleic acid sequence set forth herein as SEQ ID NO: 21. 
     
     
         34 . The method of  claim 25 , wherein the siRNA molecule comprises a nucleic acid sequence set forth herein as SEQ ID NO: 7 SEQ ID NO:7. 
     
     
         35 . The method of  claim 25 , wherein the cell is contacted with the MCJ-inhibiting compound in a pharmaceutical composition, and wherein the pharmaceutical composition further comprises a pharmaceutically acceptable carrier and optionally comprises one or more of a carrier agent, a delivery agent, a labeling agent, and a targeting agent. 
     
     
         36 - 58 . (canceled) 
     
     
         59 . The method of  claim 25 , wherein the MCJ-modulating compound further comprises a targeting agent, optionally a mitochondrial targeting agent. 
     
     
         60 . The method of  claim 35 , wherein the carrier agent comprises one or more of a nanocarrier, a cell-penetrating peptide, a polymer, a dendrimer, an siRNA bioconjugate, and a lipid-based siRNA carrier. 
     
     
         61 . The method of  claim 35 , wherein the pharmaceutical composition additionally comprises a drug known to or suspected of inducing the DILI. 
     
     
         62 . The method of  claim 35 , wherein cell is contacted with the MCJ-modulating compound at one or more of before, concurrently with, and after contacting the cell with a drug suitable to induce the DILI.