title: A novel selective androgen receptor modulator, NEP28, is efficacious in muscle and brain without serious side effects on prostate.
abstract: Age-related androgen depletion is known to be a risk factor for various diseases, such as osteoporosis and sarcopenia. Furthermore, recent studies have demonstrated that age-related androgen depletion results in accumulation of β-amyloid protein and thereby acts as a risk factor for the development of Alzheimer's disease. Supplemental androgen therapy has been shown to be efficacious in treating osteoporosis and sarcopenia. In addition, studies in animals have demonstrated that androgens can play a protective role against Alzheimer's disease. However, androgen therapy is not used routinely for these indications, because of side effects. Selective androgen receptor modulators (SARMs) are a new class of compounds. SARMs maintain the beneficial effects of androgens on bone and muscle while reducing unwanted side effects. NEP28 is a new SARM exhibiting high selectivity for androgen receptor. To investigate the pharmacological effects of NEP28, we compared the effects on muscle, prostate, and brain with mice that were androgen depleted by orchidectomy and then treated with either placebo, NEP28, dihydrotestosterone, or methyltestosterone. We demonstrated that NEP28 showed tissue-selective effect equivalent to or higher than existing SARMs. In addition, the administration of NEP28 increased the activity of neprilysin, a known Aβ-degrading enzyme. These results indicate that SARM is efficacious for the treatment of not only osteoporosis and sarcopenia, but also Alzheimer's disease.
authors.affiliation: Environmental Health Science Laboratory, Sumitomo Chemical Co., Ltd., Osaka, Japan. Electronic address: akitak@sc.sumitomo-chem.co.jp.
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Akita
authors.forename: Koichiro
authors.initials: K
authors.lastname: Harada
authors.forename: Junji
authors.initials: J
authors.lastname: Ichihara
authors.forename: Naoko
authors.initials: N
authors.lastname: Takata
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Takahashi
authors.forename: Koichi
authors.initials: K
authors.lastname: Saito
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism; D000728:Androgens / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D045744:Cell Line, Tumor; D005463:Fluoroacetates; D006367:HeLa Cells; D006801:Humans; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000254:growth & development; D015260:Neprilysin / Q000378:metabolism; D009919:Orchiectomy; D009929:Organ Size / Q000187:drug effects; D011467:Prostate / Q000187:drug effects* / Q000254:growth & development; D051381:Rats; D017207:Rats, Sprague-Dawley; D011944:Receptors, Androgen / Q000378:metabolism; D013876:Thiophenes / Q000494:pharmacology*
chemical_list: D016229:Amyloid beta-Peptides; D000728:Androgens; D005463:Fluoroacetates; C000590651:NEP28; D011944:Receptors, Androgen; D013876:Thiophenes; D015260:Neprilysin
keywords: Amyloid; Androgen; Neprilysin; SARM; Selective androgen receptor modulator