Effect of etelcalcetide on parathyroid hormone secretion by primary hyperparathyroidism patient-derived primary parathyr
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ORIGINAL ARTICLE
Effect of etelcalcetide on parathyroid hormone secretion by primary hyperparathyroidism patient‑derived primary parathyroid cells Aiko Fujioka1 · Yasuo Imanishi2 · Ikue Kobayashi2 · Tomoe Hirakawa2 · Atsuto Inoue2,3 · Kazutsune Harada2,4 · Mikiyasu Taguchi1 · Yoshihiro Sugiura1 · Hiroyuki Yamada1 · Daichi Miyaoka2 · Noriyuki Hayashi2 · Masanori Emoto2 · Masaaki Inaba2 Received: 21 May 2020 / Accepted: 17 September 2020 © The Japanese Society Bone and Mineral Research and Springer Japan KK, part of Springer Nature 2020
Abstract Introduction Etelcalcetide (Parsabiv®, AMG 416/ONO-5163) is a novel allosteric modulator for the calcium-sensing receptor approved for hemodialysis patients with secondary hyperparathyroidism of uremia. Etelcalcetide reduced parathyroid hormone levels in hemodialysis patients with secondary hyperparathyroidism of uremia in clinical studies. However, its direct effect on parathyroid hormone secretion in human parathyroid cells remains unknown. This study aimed to determine if etelcalcetide suppresses parathyroid hormone secretion by human parathyroid cells in vitro. Materials and methods We prepared primary cell cultures from human parathyroid tissue and determined calcium-sensing receptor expression levels by immunohistochemistry. Pathyroid tumors were removed from fourteen patients with primary hyperparathyrodism. Parathyroid tissue was dispersed with collagenase, resuspended in culture medium, incubated for 2 h with etelcalcetide and Ca2+, and the medium was then collected. Final etelcalcetide concentrations in the medium were 0.005– 50 µmol/L. Levels of human parathyroid hormone in the medium were determined by enzyme-linked immunosorbent assay. Results In eight of the fourteen parathyroid cell cultures, extracellular C a2+ reduced parathyroid hormone levels. In four 2+ of the eight parathyroid cell cultures which responded extracellular Ca , etelcalcetide reduced hormone secretion with the 50% effective concentrations of 0.57, 20.8, 0.42, and 0.57 µmol/L. Expression levels of the calcium-sensing receptor were significantly lower in primary hyperparathyroidism patient-derived parathyroid tissues compared with controls. Conclusion This is the first report that etelcalcetide directly reduced parathyroid hormone secretion from the primary cultured human parathyroid cells from patients with primary hyperparathyroidism. To verify this conclusion, further studies are needed using secondary hyperparathyroidism patient-derived parathyroid cells. Keywords Parathyroids · ONO-5163/AMG 416 · Calcimimetic · Calcium-sensing receptor
Introduction * Aiko Fujioka [email protected] 1
Discovery Research Laboratories, Ono Pharmaceutical Co., Ltd., 3‑1‑1 Sakurai, Shimamoto‑cho, Mishima‑gun, Osaka 618‑8585, Japan
2
Department of Metabolism, Endocrinology and Molecular Medicine, Osaka City University Graduate School of Medicine, 1‑4‑3 Asahi‑machi, Abeno‑ku, Osaka 545‑8585, Japan
3
Research Promotion, Research Project Management Division, Ono Pharmaceutical Co., Ltd., 3‑
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