Close Up - group of the month
SysKid Close up: Let’s meet P24-AMGEN & P26-UCO (University of Cordoba)
Amgen* and the University of Cordoba (UCO) are pleased to be participants in the SysKid consortium with the goal of aiding in its aspiration to develop novel concepts and therapeutics to prevent progression and treat grievous illnesses, such as diabetic nephropathy. Deeply involved in the field of mineral metabolism pathophysiology, Amgen and UCO developed a long-term and fruitful research collaboration which is integrated in the SysKid project.
Amgen (Partner 24 within the SysKid consortium) has a long standing interest in Nephrology and preventing the progression of chronic kidney disease (CKD) to end stage renal disease. Decreasing the burden of CKD’s numerous complications is a critical healthcare objective at Amgen. Amgen clinical and bench scientists have extensive expertise in the area of mineral metabolism, initially stemming from our work on the calcium sensing receptor (CaSR) pathway.
The Research group on Mineral Metabolism at the University of Cordoba led by Prof. Mariano Rodriguez Portillo, (Partner 26 within the SysKid consortium) has been doing research on mineral metabolism and vascular calcifications in CKD patients. Vascular calcification contributes to progression of renal disease and is more frequent in diabetic patients. The most recent work has been focused mainly on the CaSR and its implications in vascular calcification.
Our collaboration primarily focused on the role of calcium-sensor signaling receptor (CaSR) in vascular and soft-tissue calcification associated with CKD. With the burgeoning recognition that FGF23 plays not only a critical role in maintaining phosphate homeostasis in CKD, but that elevated levels of this hormone may also contribute to disease progression and associated co-morbidities. Both research teams have set out to better understand the biology underlying the potential “off-target” effects of FGF23 in diabetic nephropathy and CKD progression.
Towards this end, in addition to conducting preclinical studies, the Amgen team is generating tools and reagents necessary to study FGF23 biology. Studies undertaken at the University of Cordoba, in collaboration with Amgen scientists, focus on the regulation of FGF23, as well as on the potential pathological role of this molecule in CKD. This will be achieved through the development of appropriate animal models to ultimately study mechanisms by which FGF23 is involved in causing an increased vascular risk, through vascular and soft-tissue calcification and cardiovascular remodeling.
*Amgen discovers, develops, manufactures and delivers innovative human therapeutics. A biotechnology pioneer since 1980, Amgen was one of the first companies to realize the new science's promise by bringing safe, effective medicines from lab to manufacturing plant to patient. Amgen therapeutics have changed the practice of medicine, helping millions of people around the world in the fight against cancer, kidney disease, rheumatoid arthritis, bone disease and other serious illnesses. With a deep and broad pipeline of potential new medicines, Amgen remains committed to advancing science to dramatically improve people's lives. To learn more about our pioneering science and vital medicines, visit www.amgen.com.
Publications in the field from the team members:
Shalhoub V, Shatzen EM, Ward SC, Davis J, Stevens J, Bi V, Renshaw L, Hawkins N, Wang W, Chen C, Tsai MM, Cattley RC, Wronski TJ, Xia X, Li X, Henley C, Eschenberg M, Richards WG. FGF23 neutralization improves chronic kidney disease–associated hyperparathyroidism yet increases mortality. J. Clin. Invest. 2012 Jul 2;122(7):2543-53.
Rodriguez-Ortiz ME, Lopez I, Muñoz-Castañeda JR, Martinez-Moreno JM, Ramírez AP, Pineda C, Canalejo A, Jaeger P, Aguilera-Tejero E, Rodriguez M, Felsenfeld A, Almaden Y. Calcium Deficiency Reduces Circulating Levels of FGF23. J Am Soc Nephrol. 2012 Jul;23(7):1190-7
Pavik I, Jaeger P, Ebner L, Poster D, Krauer F, Kistler AD, Rentsch K, Andreisek G, Wagner CA, Devuyst O, Wüthrich RP, Schmid C, Serra AL. Soluble klotho and autosomal dominant polycystic kidney disease. Clin J Am Soc Nephrol. 2012 Feb;7(2):248-57.
Shalhoub V, Ward SC, Sun B, Stevens J, Renshaw L, Hawkins N, Richards WG. Fibroblast growth factor 23 (FGF23) and alpha-klotho stimulate osteoblastic MC3T3.E1 cell proliferation and inhibit mineralization. Calcif Tissue Int. 2011 Aug;89(2):140-50.
López I, Rodríguez-Ortiz ME, Almadén Y, Guerrero F, Montes de Oca A., Pineda C, Shalhoub V, RodrÍguez M and Aguilera-Tejero E. Direct and indirect effects of parathyroid hormone on circulating levels of fibroblast growth factor 23 in vivo. Kidney Int. 2011 Sep;80(5):475-82.
Pavik I, Jaeger P, Kistler AD, Poster D, Krauer F, Cavelti-Weder C, Rentsch KM, Wüthrich RP, Serra AL. Patients with autosomal dominant polycystic kidney disease have elevated fibroblast growth factor 23 levels and a renal leak of phosphate. Kidney Int. 2011 Jan;79(2):234-40.
Canalejo R, Canalejo A, Martinez-Moreno JM, Rodriguez-Ortiz ME , Estepa JC, Mendoza FJ , Munoz-CastanedaJR,Shalhoub V, Almaden Y, and Rodriguez M. FGF23 Fails to Inhibit Uremic Parathyroid Glands.J. Am. Soc. Nephrol., Jul 2010; 21: 1125 - 1135.
