Syros Presents on Identification of Novel Fetal Hemoglobin Repressor as Part of Broader Drug Discovery Program in Sickle Cell Disease at 61st Annual ASH Meeting
Syros Pharmaceuticals (NASDAQ:SYRS), a leader in the development of medicines that control the expression of genes, today announced that it has discovered and validated a novel fetal hemoglobin repressor, Nuclear Factor I X (NFIX), using its gene control platform. The finding sheds light on how the gamma-globin gene, which leads to the production of fetal hemoglobin, is controlled and points to new potential targets for therapeutic intervention in sickle cell disease. These data will be presented in an oral presentation tomorrow at the 61st American Society of Hematology (ASH) Annual Meeting and were highlighted today in an ASH press briefing.
“This discovery highlights the power of our platform to elucidate regulatory regions of the genome to control the expression of a single gene for therapeutic benefit,” said Eric R. Olson, Ph.D., Syros’s Chief Scientific Officer. “Based on real-world genetic and clinical data from patients, we believe it is possible to provide a functional cure for sickle cell disease by switching on the gamma-globin gene, which is typically turned off at birth, to make healthy red blood cells. Our discovery of NFIX as a critical player in silencing the gamma-globin gene opens up new potential therapeutic approaches as we advance our effort to discover an oral medicine that addresses the root cause of disease in sickle cell patients.”
The focus of Syros’ drug discovery program in sickle cell disease is to develop an oral medicine to mimic a condition found in a subset of patients, who also inherit a hereditary persistence of fetal hemoglobin (HPFH) mutation, in which the gamma-globin gene remains activated after birth. Despite having the mutated adult beta-globin gene that causes sickled cells, these patients are largely asymptomatic because the activated gamma-globin gene leads to the production of enough fetal hemoglobin for red blood cells to function normally.
Using its gene control platform, Syros scientists analyzed and compared regulatory regions of the genome in red blood cell precursors, known as erythroblasts, at various stages of maturity from fetal and adult sources to identify novel drug targets involved in the switch from fetal to adult hemoglobin expression. The genome-wide analysis pointed to NFIX as a potential fetal hemoglobin repressor. The scientists then validated the role of NFIX in silencing fetal hemoglobin by knocking down the NFIX gene in primary cells and an erythroid cell line that expresses adult hemoglobin. The data showed: