Novel Therapy for Tumor-induced Osteomalacia

DESCRIPTION (provided by applicant): Tumor-induced osteomalacia (TIO, or oncogenic osteomalacia) is an insidious, progressive, paraneoplastic disorder of abnormal phosphate and vitamin D metabolism caused by excessive fibroblast growth factor 23 (FGF23).Due to a lack of appreciation of the existence of this disease, as well as a typically slow onset of symptoms, the prevalence of TIO is most likely under-estimated. Chronically elevated FGF23 leads to renal phosphate wasting with resultant hypophosphatemiaand phosphaturia, low vitamin D, and osteomalacia, with frequent fractures. Elevated FGF23 may also lead to a) secondary hyperparathyroidism (SHPT), b) renal osteodystrophy, c) extra-skeletal calcification, and d) left ventricular hypertrophy (Tomasello,2008). Proteolytic cleavage of FGF23 produces a C-terminal peptide (FGF23c) that acts as an endogenous inhibitor of the fulllength, bioactive form of FGF23 to alleviate FGF23-mediated renal phosphate wasting (Goetz, 2010). To develop a best-in-class t