Methods and compositions to treat drug-induced diseases and conditions
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.
1. A method for treating an acetaminophen-induced liver disease or condition in a subject, the method comprising administering to a subject in need of such treatment an MCJ-inhibiting compound in an amount effective to treat the acetaminophen-induced liver disease or condition in the subject, wherein the MCJ-inhibiting compound reduces MCJ polypeptide activity in the subject and decreasing the MCJ polypeptide activity comprises decreasing one or more of an MCJ polypeptide level or activity, and wherein the MCJ-inhibiting compound comprises am MCJ small interference RNA molecule (MCJ siRNA) or an MCJ small hairpin RNA molecule (MCJ shRNA).
2. The method of claim 1 , wherein the disease or condition is an acute disease or condition.
3. The method of claim 1 , wherein the MCJ-inhibiting compound further comprises a targeting agent, optionally a mitochondrial targeting agent.
4. The method of claim 1 , wherein the MCJ siRNA molecule comprises a nucleic acid sequence set forth herein as SEQ ID NO: 21.
5. The method of claim 1 , wherein the MCJ siRNA molecule comprises a nucleic acid sequence set forth herein as SEQ ID NO: 7.
6. The method of claim 1 , wherein the MCJ-inhibiting 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.
7. The method of claim 6 , 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.
8. The method of claim 6 , wherein the pharmaceutical composition additionally comprises acetaminophen.
9. The method of claim 1 , wherein the MCJ-inhibiting compound is administered to the subject at one or more of before, concurrently with, and after ingestion by the subject of acetaminophen.
10. A method of reducing an acetaminophen-induced disease or condition in a liver cell, the method comprising contacting the liver cell with an MCJ-inhibiting compound in an amount effective to decrease an MCJ polypeptide activity in the liver cell, wherein decreasing the MCJ polypeptide activity comprises decreasing one or more of a level or function of an MCJ polypeptide in the liver cell, and wherein the MCJ-inhibiting compound comprises an MCJ small interference RNA molecule (MCJ siRNA) or an MCJ small hairpin RNA molecule (MCJ shRNA).
11. The method of claim 10 , wherein the MCJ siRNA molecule comprises a nucleic acid sequence set forth herein as SEQ ID NO: 21.
12. The method of claim 10 , wherein the MCJ siRNA molecule comprises a nucleic acid sequence set forth herein as SEQ ID NO:7.
13. The method of claim 10 , 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, a targeting agent, and acetaminophen.
14. The method of claim 10 , wherein the MCJ-inhibiting compound further comprises a targeting agent, optionally a mitochondrial targeting agent.