Abstract
Benign prostatic hyperplasia (BPH) is the most common age-related disease in men. Here we tested the efficacy of Rapatar, a micellar nanoformulation of rapamycin, in two rat models of BPH: testosterone-induced and sulpiride-induced hyperplasia in ventral lobes and lateral/dorsal lobes, respectively. We found that Rapatar prevented hypertrophic and hyperplastic abnormalities and degenerative alterations in both BPH models. Rapatar normalized weight of the lateral lobes in sulpiride-induced BPH, the most relevant animal model of human BPH. Unlike Finasteride, a standard therapy of BPH, Rapatar reduced inflammation caused by sulpiride. No obvious side effects of Rapatar were detected. Our data provide a rationale for clinical trials of Rapatar in patients suffering from BPH.
Highlights
Benign prostatic hyperplasia (BPH) is the most frequent disease in men
BPH is associated with increased incidence of prostate cancer [1]
Current treatments for BPH are based on three main strategies: inhibition of 5-α-reductase (5αR), attenuation of gonadotropin-releasing hormone, and blocking of α-adrenoreceptors
Summary
Benign prostatic hyperplasia (BPH) is the most frequent disease in men. This pathology affects 50% of men over the age 50 and 90% of men over the age 80. BPH is associated with increased incidence of prostate cancer [1]. Current treatments for BPH are based on three main strategies: inhibition of 5-α-reductase (5αR), attenuation of gonadotropin-releasing hormone, and blocking of α-adrenoreceptors. Inhibitors of 5-α-reductase (Finasteride) suppress conversion of testosterone into a more potent metabolite, 5α-dihydrotestosterone (DHT). The second strategy depends on suppression of gonadotrophin secretion, which otherwise stimulates testosterone production. Alpha-1-blockers inhibit the effect of noradrenaline on prostate smooth muscle cells, which represent more than 60% of the enlarged gland, thereby reducing prostate tone and bladder outlet obstruction [2,3,4] these medications improve lower urinary tract symptoms by less than 35-50% and cause side effects
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