The prostate is a target organ of
vitamin D receptor (VDR) agonists and represents an extra-renal site of
1,25-dihydroxyvitamin D(3) synthesis, but its capacity to respond to VDR agonists has, so far, been almost exclusively probed for the treatment of
prostate cancer. We have analyzed the capacity of VDR agonists to treat
benign prostatic hyperplasia (BPH), a complex syndrome characterized by a static component related to prostate overgrowth, a dynamic one responsible for urinary irritative symptoms, and an inflammatory component. Preclinical data demonstrate that VDR agonists, and notably
BXL-628 (
elocalcitol), reduce the static component of BPH by inhibiting the activity of intra-prostatic
growth factors downstream of the
androgen receptor, and the dynamic component by targeting bladder cells. In addition,
BXL-628 inhibits production of proinflammatory
cytokines and
chemokines by human BPH cells. These data have led to a proof-of-concept clinical study that has successfully shown arrest of prostate growth in BPH patients treated with
BXL-628, with excellent safety. We have documented the anti-inflammatory effects of
BXL-628 also in animal models of autoimmune
prostatitis, observing a significant reduction of intra-prostatic cell infiltrate following administration of this VDR agonist, at normocalcemic doses, in mice with already established disease. These data extend the potential use of VDR agonists to novel indications that represent important unmet medical needs, and provide a sound rationale for further clinical testing.