PARATHYROID-HORMONE ANALOGS FOR TREATMENT OF OSTEOPOROSIS AND HYPERCALCEMIA

Analogues of parathyroid hormone (PTH) and the parathyroid hormone rel ated peptide (PTHrP) have been proposed for the treatment of osteoporo sis and hypercalcaemia of malignancy. The endocrine PTH regulates calc ium homeostasis by its actions on bone, kidney, and intestinal recepto rs. If applied discontinuously, PTH has been shown to bring about an i ncrease in bone mass in both animal models and small-scale human trial s. The locally produced paracrine PTHrP is secreted in abundance by so me rumours, re suiting in severe hypercalcaemia. Numerous analogues of PTH, designed to have improved or more specific activities or to be m ore readily delivered, have been described in the patent literature as being possibly more effective than native PTH for osteoporosis treatm ent. Inactive analogues of PTHrP, which retain tight binding to the PT H/PTHrP receptor, have been proposed for the treatment of hypercalcaem ia of malignancy. Related patent activities on the production of PTH b y recombinant technologies and on the delivery of peptides by tracheal and oral routes are also discussed.