CaSR Human Research

Current research based on MariCal Co-Founders initial discoveries shows that serum Ca²⁺ itself permits the integration of multiple complex physiological processes, with CaSRs as the master switches. As illustrated below, Co-Founder research efforts in mammals show that small changes in serum Ca²⁺ concentrations are sensed by CaSRs in multiple organs that function together to control and integrate a host of physiological processes.

CaSRs are master switches for ion and water metabolism in humans. CaSR sensing functions control a large number of key physiological processes in various organs to provide for a coordinated response to changes in body Ca²⁺ , Na+ and water.

These organs include brain, parathyroid gland, kidney, gastrointestinal tract and bone. For example, it is well known that elevations in serum Ca²⁺ are deleterious to many cellular functions and therefore mammals respond rapidly with corrective actions to lower serum Ca²⁺ levels to prevent these effects. Actions which decrease serum Ca²⁺ include: 1) reducing Ca²⁺ reabsorption from calcium-rich bone, increasing the excretion of Ca²⁺ by the kidney, reducing the absorption of Ca²⁺ from the gastrointestinal tract and increasing thirst to provide for increased water intake to enable more rapid removal of Ca²⁺ by the kidney. Remarkably, all of the above processes are directly regulated by CaSR activation that provides an integrated response to control and reduce systemic hypercalcemia.

Based on the central role of CaSRs to regulate plasma Ca²⁺ and parathyroid hormone secretion in humans, pharmaceutical drug development efforts by NPS Pharmaceuticals Inc. and Amgen Inc have resulted in the successful marketing and sales of the CaSR-modulator, Sensipar^®, for use in humans with endocrine and/or renal diseases. In addition, active human drug development efforts are also underway at companies such as Kirin Pharmaceuticals and GlaxoSmithKline Pharmaceuticals Inc. with CaSR-based R+D efforts pursuing major diseases such as osteoporosis as targets.