Catabolic Wasting - Cachexia and Sarcopenia
Novel and Emerging Treatments
Myostatin is a naturally-produced protein that limits muscle growth and is often found in relatively high levels in patients with cachexia, sarcopenia, and osteoporosis (Buehring 2013; Elliot 2012). Myostatin is also significantly higher in smokers versus non-smokers, probably due to the complex mixture of toxins in cigarette smoke (Rom 2012; Petersen 2007).
Research is currently underway to develop therapies that could increase muscle and bone mass by reducing myostatin activity in the body (Buehring 2013; Elliot 2012; Attie 2013). A double-blind study in 48 healthy postmenopausal women reported that a single dose of the experimental drug ACE-031 (which inhibits myostatin activity) produced a 5.1% increase in thigh muscle volume compared to a 0.2% reduction in women given placebo (Attie 2013).
There is ongoing research investigating the possible use of beta-adrenergic drugs like formoterol (Foradil®) to prevent or reverse the muscle wasting and weakness associated with cachexia and sarcopenia. Beta-adrenergic drugs are believed to help build and maintain muscle by a number of pathways that reduce protein breakdown and increase protein synthesis. However, they do have a number of possible side effects, including heart problems and insomnia (Koopman 2009; Lee 2013).
Selective Androgen Receptor Modulators
Selective androgen receptors modulators (SARMs) like the investigational drug enobosarm (Ostarine® or GTx-024) have tissue-specific anabolic effects in the muscles and bones while at the same time lacking other androgenic effects, such as hair growth in women and adverse effects on the prostate in men. Enobosarm was found to significantly increase lean muscle mass and muscle function in a group of 120 older adults (Dalton 2011).
The investigational anti-cancer drug selumetinib may be useful for cachectic cancer patients by reducing production of IL-6, which causes inflammation and may reduce muscle mass. In a placebo-controlled study of bile duct cancer patients treated with selumetinib for 100 days, muscle mass increased an average of 5.1 pounds in the treatment group and decreased an average of 2.6 pounds in the placebo group (Prado 2012).
Ghrelin treatment has also been observed to increase appetite in people with muscle wasting. Ghrelin is a hunger-stimulating peptide (small protein) primarily produced by the stomach and small intestines. Ghrelin also plays a role in stimulating gastrointestinal motility, reducing inflammation, and stimulating growth hormone release by the pituitary gland. A number of human studies have reported that intravenous or subcutaneous treatment with ghrelin or ghrelin mimetics is associated with increased appetite, muscle and fat mass, and functional status in people with sarcopenia, cancer, COPD, and end stage renal disease (Guillory 2013). Currently, a number of clinical trials are underway to examine the possible effects of ghrelin and related compounds on improving appetite in muscle-wasted individuals.