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Sarcopenia and Androgens: A Link Between Pathology and Treatment
Published in Chad Cox, Clinical Nutrition and Aging, 2017
Carla Basualto-AlarcÓN, Diego Varela, Javier Duran, Rodrigo Maass, Manuel Estrada
Supplementation with selective androgen-receptor modulators (SARMs) has emerged as a means of treating muscle and bone disorders, mainly because of the specificity of SARM action and the relatively few side effects of SARM treatment. Research using experimental models has demonstrated that administration of SARM S-4 exerts potent anabolic effects on skeletal muscle and bone and only minimal effects on the prostate (97). In a recent randomized, double-blind, placebo-controlled study of 170 women aged ≥65 with sarcopenia and moderate physical dysfunction found that 6 months of treatment with MK-0773 significantly improved physical performance measures (98). GTx-024 (enobosarm), a non-steroidal SARM that exerts tissue-selective anabolic effects in muscle and bone while sparing other androgenic tissue related to hair growth in women and prostate effects in men, has demonstrated promising pharmacologic effects in preclinical studies and favorable safety and pharmacokinetic profiles in phase I investigations. Thus GTx-024 supplementation resulted in dose-dependent improvement in total lean body mass and physical function and was well tolerated (99). Treatment with one or more of the numerous other SARMs currently under study may emerge as therapeutic alternatives to androgen agonist therapy. The intense research into pharmacological modulation of androgens and androgen intracellular signaling pathways may lead to the development of effective approaches to restoring and preventing the muscle loss observed in sarcopenia.
Current advancements in pharmacotherapy for cancer cachexia
Published in Expert Opinion on Pharmacotherapy, 2023
Guilherme Wesley Peixoto da Fonseca, Ryosuke Sato, Maria Janieire de Nazaré Nunes Alves, Stephan von Haehling
Considering the typical side effects associated with testosterone therapy, selective androgen receptor modulators (SARMs), an antagonistic/mildly agonistic androgenic receptor, have been also introduced to treat cancer cachexia. Enobosarm has shown to increase LBM and stair climb power in patients with cancer cachexia after a dose of 1 and 3 mg [108], which were documented to be well tolerated. A large randomized, multi-center clinical trial in phase III, the POWER trials (POWER 1, NCT01355484 and POWER 2, NCT01355497), demonstrated that Enobosarm in POWER 1 and 2 increased LBM at time point 84 and 147 days and showed a lower body weight decline compared with placebo [109]. However, we are still missing robust studies with SARMs in patients with cancer cachexia.
Therapeutic considerations of sarcopenia in heart failure patients
Published in Expert Review of Cardiovascular Therapy, 2018
Masakazu Saitoh, Nicole Ebner, Stephan von Haehling, Stefan D. Anker, Jochen Springer
SARMs, a class of androgen receptor ligands, may have potential as beneficial strategy for sarcopenia. Phase II A randomized, placebo-controlled clinical trial to study the efficacy and safety of the SARMs, MK-0773 for elderly subjects with sarcopenia. Participants receiving MK-0773 showed a significant increase in lean body mass relative to placebo (p < 0.001), but no significant improvement in muscle strength or physical performance [92]. Moreover, enobosarm, a recently developed SARM, has shown beneficial treatment strategy for muscle wasting in patients with cancer patients [93]. Several studies have shown beneficial effects of SARMs on muscle strength, physical performance, and sarcopenia, however there was no evidence in HF patients.
Selective androgen receptor modulators (SARMs) as pharmacological treatment for muscle wasting in ongoing clinical trials
Published in Expert Opinion on Investigational Drugs, 2020
Guilherme Wesley Peixoto Da Fonseca, Elke Dworatzek, Nicole Ebner, Stephan Von Haehling
Enobosarm, also known as GTx-024, ostarine, MK-2866 and/or S-22, is an oral, non-steroidal SARM that has been developed by GTx Inc., since June 2019 under the name Oncternal Therapeutics. This compound was patented by James T. Dalton, Duane D. Miller and Karen A. Veverka in 2005 (WO2005120483A2) and since then it has been under development to treat patients with muscle wasting. In November 2007, GTx and Merck announced a 3-year agreement for research and development of enobosarm [33]. According to GTx Inc., there have been 25 studies with enobosarm conducted, which enrolled over 1,700 subjects [34]. In a statement dated 4 April 2014, the company estimated that 35 million US dollars had been invested in the development of enobosarm [35].