Clinical anticachexia treatments.
Cachexia involves progressive loss of adipose tissue and skeletal muscle mass and is common in a number of end-stage diseases. Cachexia causes weakness and immobility, reduces the quality of life of the patient, and eventually results in death. We reviewed the medical literature concentrating upon agents that have undergone clinical evaluation for the treatment of patients with cachexia. These agents are discussed, together with their mechanisms of action. Megestrol acetate, corticosteroids, eicosapentaenoic acid, and thalidomide have shown some success in the treatment of cachexia. beta-hydroxy-beta-methylbutyrate, cyclooxygenase inhibitors, adenosine 5'-triphosphate, and growth hormone are undergoing clinical evaluation. Appetite stimulants such as cannabinoids and antiserotonic agents have been shown to be ineffective in preventing progressive weight loss in cachexia. Much of the success in the treatment of cachexia has come from agents capable of blocking protein degradation through the ubiquitin-proteasome proteolytic pathway. Muscle mass can be increased when such agents are combined with agents that stimulate protein synthesis. In order to develop new agents, more fundamental research is required on the cellular mechanisms governing protein synthesis and degradation in skeletal muscle in cachexia.
Molecular Biosciences, School of Life and Health Sciences, Aston University, Birmingham B4 7ET, United Kingdom. m.j.tisdale@aston.ac.uk
Michael J
MJ
Tisdale
D000273:Adipose Tissue / Q000378:metabolism*; D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D002100:Cachexia / Q000188:drug therapy* / Q000378:metabolism*; D015118:Eicosapentaenoic Acid / Q000627:therapeutic use; D004734:Energy Metabolism / Q000502:physiology; D006801:Humans; D018482:Muscle, Skeletal / Q000378:metabolism*; D011372:Progestins / Q000627:therapeutic use; D014176:Protein Biosynthesis; D013792:Thalidomide / Q000627:therapeutic use
D000305:Adrenal Cortex Hormones; D011372:Progestins; D013792:Thalidomide; D015118:Eicosapentaenoic Acid