Methods and compositions to treat drug-induced diseases and conditions

Patent metadata

Field	Value
Publication number	US-2020283770-A1
Application number	US-202016876503-A
Country	US
Kind code	A1
Filing date	May 18, 2020
Priority date	Jul 10, 2015
Publication date	Sep 10, 2020
Grant date	—

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.

First claim

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.

Assignees

• Univ Of Vermont And State Agricultural College
• Asociacion Centro De Investig Cooperativa En Biociencias Cic Biogune

Inventors

• Rincon Mercedes
• Martinez Chantar Maria Luz
• Anguita Juan
• Dienz Oliver

Classifications

• C12N2310/14

  interfering nucleic acids [NA] · CPC title

• A61K31/7105

  Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links · CPC title

• C12N15/113 Primary

  Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; {Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing (when used in plants C12N15/8218)} · CPC title

• A61P13/12

  of the kidneys · CPC title

• A61P1/16

  for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics · CPC title