Description of Invention:
Parathyroid hormone receptors found on osteoblasts in bone and renal tubule cells in kidney elevate blood calcium levels when stimulated by parathyroid hormone (PTH) and PTH-related protein (PTHrP). Excessive secretion of PTH from the parathyroid gland results in primary hyperparathyroidism. Production of PTHrP by various tumors results in humoral hypercalcemia of malignancy. In both of these conditions, excessive blood calcium levels lead to clinically significant morbidity. A parathyroid hormone antagonist could therefore have therapeutic value.
Until now, no effective antagonists for the classical parathyroid hormone receptor (PTH1 receptor) were known. This invention describes a peptide which binds with high affinity (Kd = 1.3 +/- 0.1 nM, dissociation T1/2 = 14 min.) and acts as purely competitive antagonist at the PTH1 receptor. This novel peptide is related to tuberoinfundibular peptides of 39 residues (TIP39), also described in this invention, which binds to a related receptor. Deletion of amino acids from the N-terminus of TIP39 resulted in the high affinity PTH1 receptor antagonist peptide described here. This peptide may be used therapeutically to treat excessive blood calcium caused by PTH or PTHrP, other pathology caused by PTHrP, to demonstrate the utility of parathyroid hormone receptor antagonism in the treatment of hypercalcemia or other conditions, or to help screen for other antagonists at the parathyroid hormone receptor.
Inventors:
Ted B. Usdin and Samuel R. Hoare (NIMH)
Patent Status:
DHHS Reference No. E-123-1999/0 --
U.S. Provisional Application No. 60/139,335 filed 15 Jun 1999
PCT Application No. PCT/US00/16776 filed 15 Jun 2000
U.S. Patent Application No. 10/014,162 filed 11 Dec 2001
Portfolios: Internal Medicine Central Nervous System
Central Nervous System -Therapeutics-Neurological Therapeutics-Muscle Relaxants Internal Medicine-Therapeutics-Cardiology-Antihypertensive Central Nervous System -Therapeutics Internal Medicine-Diagnostics Internal Medicine-Therapeutics
For Additional Information Please Contact: Norbert J. Pontzer PhD JD
NIH Office of Technology Transfer
6011 Executive Blvd, Suite 325
Rockville, MD 20852-3804
Phone: (301) 435-5502
Email: pontzern@mail.nih.gov
Fax: (301) 402-0220
