Developing models for cachexia and their implications in drug discovery.
BACKGROUND
Cachexia is a complex metabolic syndrome associated with underlying illness and characterized by loss of muscle with or without loss of fat mass. Systemic inflammation plays a central role in its pathophysiology. As millions of patients are in a cachectic state of chronic disease, cachexia is one of the major causes of death worldwide. Difficulties in the recruitment and follow-up of clinical trials mean that well-characterized animal models are of great importance in developing cachexia therapies. However, some of the widely used animal models have limitations in procedural reproducibility or in recapitulating in the cachectic phenotype, which has warranted the development of novel models for cachexia.


METHODS
This review focuses on some of the currently developing rodent models designed to mimic each co-morbidity in cachexia.


CONCLUSIONS
Through developing cancer models, researchers have been seeking more targets for intervention. In cardiac cachexia, technical issues have been overcome by transgenic models. Furthermore, the development of new animal models has enabled the elucidation of the roles of inflammation, anabolism/catabolism in muscle/fat tissue and anorexia on cachexia. As metabolic and inflammatory pathways in cachexia may compromise cardiac muscle, the analysis of cardiac function/tissue in non-cardiac cachexia may be a useful component of cachexia assessment common to different underlying diseases and pave the way for novel drug discovery.
University Medical Centre Göttingen, Institute of Innovative Clinical Trials , Robert-Koch-Str. 40, 37075 Göttingen , Germany ; +49 0 551 39 6380 ; +49 0 551 39 6389 ; m_koni524@hotmail.com.
Masaaki
M
Konishi
Nicole
N
Ebner
Stephan
S
von Haehling
Stefan D
SD
Anker
Jochen
J
Springer
D000818:Animals; D002100:Cachexia / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D004195:Disease Models, Animal; D055808:Drug Discovery / Q000379:methods; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology; D009369:Neoplasms / Q000150:complications*; D015203:Reproducibility of Results; D012377:Rodentia
animal models; cachexia; inflammation; wasting