By Silvia Busquets Rius, University of Barcelona
Cachexia is defined as a state of malnutrition and physical exhaustion and includes weight loss (up to 80% of lean and fat mass) due to a chronic disease. Cachexia occurs in many diseases such as cancer, acquired immunodeficiency syndrome, sepsis, diabetes, states immobilization, severe burns, chronic obstructive pulmonary disease, cardiovascular disease or old age, among others. In particular, cancer cachexia appears in different degrees of severity in about half of cancer patients and is associated with more than 20% of cancer deaths.
The social impact of a new therapy would be significant, since cachexia syndrome is present in many diseases that affect a large number of patients. The scientific community is concerned with finding suitable drugs to combat cachexia so that the patients affected can enjoy a higher quality of life. This improvement would lead to physical health and also an improved mental capacity, which would substantially facilitate the fight against the disease.
Nowadays there is no effective pharmaceutical treatment on the market that can resolve cachexia. Today, patients suffering with cachexia receive treatments (that is, if they are treated; it is not a common hospital practice) based on different types of drugs, which are mainly derived from progesterone (in particular, megestrol acetate) and steroids such as testosterone, nandrolone or ostarine.
Our research group found that an agonist of the beta2-adrenergic receptor, formoterol, has a highly potent anti-cachectic efficiency with fewer adverse side effects and less toxicity. The active ingredient formoterol is widely known because it is used for treatment of bronchospasm, a problem associated with asthma. From this discovery the University of Barcelona has filed a patent that states the use of formoterol in the prophylactic, therapeutic and symptomatic treatments of cachexia. A pharmaceutical company now owns the license to the patent and is currently conducting a Phase IIA clinical study with patients in an Edinburgh hospital to verify formoterol’s anti-cachectic usefulness at the human level.
The abnormalities associated with cachexia include alterations in carbohydrate, lipid and protein metabolism, alterations that are also often associated with anorexia. Concerning the therapeutic approaches, one can speculate that a single round of therapy may not be completely successful in the treatment of cachexia. From this point of view, combinations of treatments are more likely to be successful. In fact, patients on total parenteral nutrition are still subject to extreme weight loss, which emphasizes the role of the metabolic abnormalities associated with cachexia.
It is perhaps for this reason that any therapeutic approach based on increasing food intake has to be combined with a pharmacological strategy to counteract metabolic changes. Moreover, timing is very important and has to be seriously considered when designing the therapeutic approach: any nutritional/metabolic/pharmacological support should be started early in the course of the disease before severe weight loss occurs.
The future treatment of the cachectic syndrome will no doubt combine different pharmacological approaches to efficiently reverse the metabolic changes described above and, at the same time, ameliorate the anorexia of the patients. Defining this therapeutic combination of drugs is a rewarding project that will stimulate many scientific efforts and relieve suffering.
Silvia Busquets Rius
University of Barcelona
www.atomiumculture.eu
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