Compositions and Methods For Treating Cachexia

Abstract

The present invention relates, in various embodiments, to methods of treating cachexia (e.g., cancer cachexia) in a patient. The methods comprise administering at least one compound for inhibiting, in alternative embodiments, the expression or activity of a microRNA that is present in microvesicles secreted from cancer cells in the patient (e.g., a miR-21 gene product), the expression or activity of a Toll-like receptor (e.g., TLR7, TLR8), the expression or activity of a c-Jun N-terminal kinase (JNK), the secretion of microvesicles from cancer cells, or the fusion of microvesicles from cancer cells with muscle cells or adipocytes. The present invention also relates, in certain embodiments, to pharmaceutical compositions comprising at least two compounds useful in the practice of the methods of the invention described herein.

What is claimed is: 
     
         1 . A method of treating cachexia in a patient in need thereof, comprising administering to the patient an effective amount of at least one compound for inhibiting the expression or activity of a miR-21 gene product. 
     
     
         2 . The method of  claim 1 , wherein the miR-21 gene product is a mature miR-21 RNA. 
     
     
         3 . The method of  claim 1 , wherein the miR-21 gene product is a pre-cursor miR-21 RNA. 
     
     
         4 . The method of  claim 1 , wherein the compound inhibits binding of the miR-21 gene product to a Toll-like receptor 7 (TLR7 receptor) or a Toll-like receptor 8 (TLR8 receptor). 
     
     
         5 . The method of  claim 1 , wherein the compound is an antisense nucleic acid that binds to a miR-21 gene product. 
     
     
         6 . The method of  claim 1 , wherein the compound is a double-stranded RNA molecule having at least 90% sequence homology with a miR-21 gene product. 
     
     
         7 . The method of  claim 1 , wherein the compound is a ribozyme. 
     
     
         8 . The method of  claim 1 , wherein the patient has cancer. 
     
     
         9 . The method of  claim 8 , wherein the cancer is lung cancer. 
     
     
         10 . The method of  claim 8 , wherein the cancer is pancreatic cancer. 
     
     
         11 . The method of  claim 8 , wherein the cancer is gastric cancer. 
     
     
         12 . The method of  claim 8 , wherein the cancer is esophageal cancer 
     
     
         13 . The method of  claim 8 , wherein the cancer is duodenal cancer. 
     
     
         14 . The method of  claim 1 , wherein a nucleic acid that expresses the compound for inhibiting the expression of a gene encoding a miR-21 gene product is administered to the patient. 
     
     
         15 . The method of  claim 1 , wherein the patient is a human. 
     
     
         16 . A method of treating cachexia in a patient in need thereof, comprising administering to the patient an effective amount of at least one compound for inhibiting the expression or activity of a Toll-like receptor 7 (TLR7 receptor) or a Toll-like receptor 8 (TLR8 receptor), at least one compound for inhibiting the expression or activity of a c-Jun N-terminal kinase (JNK), at least one compound for inhibiting secretion of microvesicles from cancer cells in the patient, at least one compound for inhibiting fusion of microvesicles from cancer cells with muscle cells or adipocytes in the patient, or at least one compound for inhibiting fusion of microvesicles from cancer cells with muscle cells or adipocytes in the patient. 
     
     
         17 . A pharmaceutical composition comprising at least two compounds selected from the group consisting of a compound for inhibiting the expression or activity of a microRNA that is present in microvesicles secreted from cancer cells, compound for inhibiting the expression or activity of a Toll-like receptor 7 (TLR7 receptor) or a Toll-like receptor 8 (TLR8 receptor), a compound for inhibiting the expression or activity of a c-Jun N-terminal kinase (JNK), a compound for inhibiting secretion of microvesicles from cancer cells, and a compound for inhibiting fusion of microvesicles from cancer cells with muscle cells or adipocytes, or pharmaceutically-acceptable salts thereof. 
     
     
         18 . The pharmaceutical composition of  claim 17 , further comprising a pharmaceutically-acceptable carrier. 
     
     
         19 . A method of treating cancer cachexia in a patient in need thereof, comprising administering to the patient an effective amount of the composition of  claim 17 . 
     
     
         20 . The method of  claim 19 , further comprising administering to the patient an effective amount of at least one compound for inhibiting the expression or activity of a microRNA that is present in microvesicles secreted from cancer cells in the patient, wherein the microRNA is miR-27b, miR-29a, miR-92a, miR-126, miR-133, miR-146, miR-147, miR-155 or miR-574-5p, or a combination thereof.