Therapeutics: Kelch-like ECH-associated protein 1 (KEAP1); nuclear factor (erythroid-derived 2)-like 2 (NFE2L2; NRF2)

Mouse studies suggest inhibiting KEAP1 or activating NFE2L2 could help treat sickle cell disease. In a mouse model of sickle cell disease, KEAP1 knockdown increased NFE2L2 levels in the liver and lung and decreased disease-associated liver necrosis and lung infiltration by inflammatory cells compared with normal KEAP1 expression. Also in the mouse model, an NFE2L2-activating tool compound decreased liver necrosis and levels of inflammatory cytokine mRNA in the lung compared with vehicle. Next steps could include testing other NFE2L2-activating compounds in mouse models of sickle cell disease.

Biogen Inc. and UCB Group market Tecfidera dimethyl fumarate, an oral dimethyl fumarate that activates the NFE2L2 pathway, to treat multiple sclerosis (MS). ...