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Selective androgen receptor modulators (SARMs) - potential anabolic drugs for the treatment of cachexia and frailty
Rafał Borecki1, Piotr Byczkiewicz1, Jolanta Słowikowska-Hilczer2
1Department of Andrology and Reproductive Endocrinology, Medical University of Lodz, Lodz, Poland.
Abstract:
Cachexia is characterized by decreased body weight resulting from the predominance of catabolic over anabolic metabolism. The condition is likely to be caused by a decline in the body's physiological reserves, which leads to breakdown of homeostatic processes in patients weakened by diseases. The overlapping disease is the frailty syndrome, i.e., a group of symptoms (decreases in skeletal muscle mass (sarcopenia) and bone density) that occur in the aging process. Additionally, cachexia is associated with elevated levels of various pro-catabolic indicators. Importantly, this condition responds rather poorly to standard nutritional support or medical nutrition, and is often accompanied by loss of appetite, which makes therapy much more difficult. The result is worsening of the patient's somatic condition and an increased risk of premature death. Compounds representing the class of selective androgen receptor modulators (SARMs) are a relatively new group of substances that could be used in the future to improve the condition of patients with cachexia and frailty syndrome. Two compounds, GTx-024/MK-2866 (enobosarm) and GSK2881078, are currently being tested in clinical trials. This paper discusses their effects and potential use in future cachexia and frailty therapies.
Insights
Selective androgen receptor modulators (SARMs) show promise for treating cachexia and frailty syndrome. These conditions involve muscle loss and poor response to nutrition, but SARMs like enobosarm may offer new therapeutic options.
Area of Science:
- Gerontology
- Metabolic Disorders
- Pharmacology
Background:
- Cachexia involves decreased body weight due to imbalanced metabolism, often seen in weakened patients.
- Frailty syndrome, linked to aging, includes sarcopenia (skeletal muscle mass loss) and reduced bone density.
- Cachexia is difficult to treat with standard nutrition and often involves appetite loss, worsening patient outcomes.
Purpose of the Study:
- To review the potential of selective androgen receptor modulators (SARMs) in treating cachexia and frailty syndrome.
- To discuss the clinical trial status and therapeutic implications of specific SARMs.
Main Methods:
- Literature review of cachexia, frailty syndrome, and selective androgen receptor modulators.
- Analysis of current clinical trial data for SARMs like enobosarm and GSK2881078.
Main Results:
- Selective androgen receptor modulators (SARMs) represent a novel therapeutic class for cachexia and frailty.
- Compounds GTx-024/MK-2866 (enobosarm) and GSK2881078 are under investigation in clinical trials.
- SARMs may offer a future treatment avenue for these debilitating conditions.
Conclusions:
- Selective androgen receptor modulators (SARMs) hold potential for improving cachexia and frailty syndrome.
- Further research and clinical trials are necessary to establish the efficacy and safety of SARMs in patient populations.
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