Silence Therapeutics plc announced publication of human genomic and in vivo preclinical data linking iron regulation to polycythemia vera (PV) in the latest issue of Blood, the medical journal of the American Society of Hematology (ASH). The paper is authored by senior medical and scientific experts from Silence and leading population health and hematology researchers from WEHI (Walter and Eliza Hall Institute) in Melbourne, Australia as well as Cambride UK. The research, led by WEHI's Dr Cavan Bennett and Professor Sant-Rayn Pasricha, identified links between PV and variants of the iron-regulating gene HFE in a genomewide association study (GWAS) of 440 PV cases and over 400,000 healthy controls.

The study further demonstrated in a mouse model of PV that hepcidin, a master regulator of iron availability whose expression is influenced by HFE, governs the red blood cell (erythroid) phenotype in PV. SLN124, an siRNA (short interfering RNA) targeting TMPRSS6, is currently being studied in the SANRECO phase 1/2 study in adults with PV. SLN124 is also being studied in other hematological disorders such as beta thalassemia.

SLN124 works by silencing TMPRSS6, a gene that negatively regulates hepcidin expression, to increase production of hepcidin in the liver.