Silence Therapeutics Announces Publication in Blood Demonstrating Role for Iron Regulation in Polycythemia Vera

Silence Therapeutics, an experienced and innovative biotechnology company committed to transforming people’s lives by silencing diseases through precision-engineered medicines, today announced the 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 polycythemia vera 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.

“The phenotype of PV involves the over-production of red blood cells, leading to a range of adverse symptoms and a high risk of life-threatening cardiovascular events,” said Dr. Ute Schaeper, Drug Discovery Project Leader at Silence and a co-author on the paper. “The results we reported in Blood provide a genetic and biological rationale for treating PV with SLN124 by raising hepcidin to control systemic iron levels, thus reducing red blood cell count. This therapeutic approach could potentially prevent the need for patients to undergo periodic blood withdrawals to treat their disease and reduce their risk of cardiovascular events without the fluid shifts and severe iron deficiency associated with phlebotomies.”

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.