Grant: Proof of Principle Program Phase I - Drug Development

We have developed and synthesized a bone-seeking variant of the peptide hormone Calcitonin, which is currently used to treat bone conditions such as Osteoporosis. When unaltered Calcitonin is given to a patient, it is distributed systemically to all tissues of the body, thereby reducing the effectiveness of the given drug dosage. Unlike the parent molecule, our bisphosphonate-conjugated Calcitonin will immediately target to and coat the bones of the patient after drug administration and resist the body's bone resorption events that follow to great effect, thereby reducing bone fracture in Osteoporosis patients. We hypothesize that the BP-targeted delivery of Calcitonin to bone will increase its concentration to bone cell receptors at the site of its desired antiresorptive action, relative to its presentation to Calcitonin receptors in other organs and cells. The BP-conjugated Calcitonin described in this proposal represents a new class of bone-targeting antiresorptive compounds, which could find clinical utility in the treatment of Osteoporosis and related bone disease indications including Paget's disease, osteolytic tumors, Rheumatoid Arthritis, Ankylosing Spondylitis, Osteoarthritis, drug-induced osteopenia, and hypercalcemia. Our bone-targeting strategy would improve the antiresorptive efficacy of Calcitonin, whilst minimizing drug toxicity and non-specific side-effects, thereby improving patient compliance and quality of life.