By Iris Becene
The aging population has lead to a great demand for treatments for diseases such as osteoporosis, and Patrick R. Griffith, co-chair of the TSRI Department of Molecular Medicine, is addressing just that. Using hydrogen-deuterium exchange mass spectrometry, the Griffith lab is able to map specific regions of the Vitamin D receptor which is responsible for regulating calcium levels in the blood. Currently, osteoporosis drugs that target this receptor cause hypercalcemia and are used sparingly because this condition leads to kidney stones and weakened bones. The lab hopes to stop the development of this condition by creating dissociated vitamin D receptor ligands, or 1,25D3 analogs, that do not activate the TRPV6 gene, or the gene that causes hypercalcemia. Instead, these analogs would target the BGLAP gene and prohibit it from activating the TRPV6 gene. The BGLAP gene is important in controlling bone mineralization.
The main aim of the lab is to develop an in depth picture of how the Vitamin D receptor works and the structural mechanisms of how it reacts with different ligands. Using technologies that create a clear picture of how protein conformation affects different molecular interactions, new medicines that only target genes that do not cause hypercalcemia can be used.
Scripps Research Institute. (2017, October 13). 'Roadmap' to aid osteoporosis treatment development. ScienceDaily. Retrieved October 21, 2017 from www.sciencedaily.com/releases/2017/10/171013132224.htm