cachexia

Cachexia (pronounced /kəˈkɛksiə/, from Greek kakos and hexia: bad condition^[1]) is loss of weight, muscle atrophy, fatigue, weakness and significant loss of appetite in someone who is not actively trying to lose weight. The formal definition of cachexia is the loss of body mass that cannot be reversed nutritionally; even if you supplement the patient calorically, lean body mass will be lost, indicating there is a fundamental pathology in place. Cachexia is seen in patients with cancer, AIDS, COPD (chronic obstructive pulmonary disease), CHF (congestive heart failure) and Familial Amyloid Polyneuropathy. It is a positive risk factor for death—meaning if the patient has cachexia, the chance of death from the underlying condition is increased dramatically. It can be a sign of various underlying disorders; when a patient presents with cachexia, a doctor will generally consider the possibility of cancer, metabolic acidosis (from decreased protein synthesis and increased protein catabolism), certain infectious diseases (e.g. tuberculosis, AIDS), and some autoimmune disorders, or addiction to drugs such as amphetamines or cocaine. Cachexia physically weakens patients to a state of immobility stemming from loss of appetite, asthenia, and anemia, and response to standard treatment is usually poor.^[2][3]

Disease settings

Cachexia is often seen in end-stage cancer, and in that context is called "cancer cachexia". It was also prevalent in HIV patients before the advent of highly active anti-retroviral therapy (HAART) for that condition; now it is seen less frequently in those countries where such treatment is available. In those patients who have congestive heart failure, there is also a cachectic syndrome. Also, a cachexia co-morbidity is seen in patients that have any of the range of illnesses classified as "COPD" (chronic obstructive pulmonary disease), particularly emphysema. Some severe cases of schizophrenia can present this condition where it is named vesanic cachexia^{[citation needed]} (from vesania, a Latin term for insanity).

In each of these settings there is full-body wasting, which hits the skeletal muscle especially hard, resulting in muscle atrophy and great muscle loss.

Mechanism

The exact mechanism in which these diseases cause cachexia is poorly understood, but there is probably a role for inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α)—which is also nicknamed cachexin (also spelled cachectin) for this reason, Interferon gamma (IFNγ), and Interleukin 6 (IL-6), as well as the tumor-secreted proteolysis inducing factor (PIF).

Related malnutrition syndromes are kwashiorkor and marasmus, although these do not always have an underlying causative illness; they are most often symptomatic of severe malnutrition.

Those suffering from the eating disorder anorexia nervosa appear to have high plasma levels of ghrelin. Ghrelin levels are also high in patients who have cancer-induced cachexia.^[4]

Treatment

Cachexia can be treated by steroids such as corticosteroids or drugs that mimic progesterone, which increase appetite and may reverse weight loss.^[5] Hydrazine sulfate was investigated as a treatment for cancer-associated cachexia, but was found to be ineffective. Medical Marijuana has been approved for the treatment of cachexia in some states such as Oregon and California.^[5][6]

Currently, there is no widely accepted drug to treat cachexia, but best estimates value a potential market at around $500 Million annually in the U.S. and over $1 billion globally.^[7] The world's leading scientists gathered at the 5th annual meeting of the Society on Cachexia and Wasting Disorders in Barcelona December 5–8, 2009 to present data on various molecules in development. Two of the presenting companies were Cytokinetics and Ohr Pharmaceutical. Cytokinetics' molecule acts as a skeletal muscle activator by making certain proteins more sensitive to calcium. Potential treatment for diseases and conditions associated with aging, muscle wasting or neuromuscular dysfunction. Ohr Pharmaceutical's drug, AVR 118, modulates pro-inflammatory chemokine and cytokine synthesis, including TNF-alpha. During the past decade, researchers have adduced much evidence supporting the critical roles of cytokines in the production of Cachexia. In addition, the drug has shown to have chemoprotective effects, allowing patients to tolerate higher doses, and more intensive treatment regimens, with ordinarily toxic chemotherapeutic agents.

GTx has partnered with Merck to develop Ostarine (TM) for a host of musculoskeletal wasting conditions. Ostarine is a SARM (selective androgen receptor molecule), a relatively new class of small molecule nuclear hormone receptor modulators that shows promise for improving the benefits of testosterone treatments while minimizing the undesirable side effects. They also have the potential advantages of oral dosing and tissue selectivity.

See also

• Wasting

References

External links

• Manifestations and treatment of cachexia, from Cancer Medicine
• Scientists find key to 'wasting syndrome' seen in cancer, AIDS (U.S. Department of Veterans Affairs)