SLN124: a conjugated siRNA for iron overload
In hereditary hemochromatosis, gene mutations in the hepcidin-ferroportin axis controlling iron homeostasis, lead to hepatic iron overload. Hepcidin is predominantly produced by the liver and is induced by activation of the BMP/SMAD signalling pathway.
The hormone is furthermore under the negative control of the transmembrane serine protease matriptase-2, encoded by the TMPRSS6 gene. Dr. Ute Schäper (Max-Delbrück-Centrum für Molekulare Medizin, Berlin, Germany) presented the results of a study aimed to identify and characterize SLN124, an siRNA conjugated to a GalNAc ligand, targeting TMPRSS6 expression.
“SLN124 was well tolerated and showed dose-dependent and long-lasting effects on target expression, on modulation of iron stores and on normalization of erythropoiesis in beta-thalassemia mice.” SLN124 is planned to enter clinical development by the end of 2018.