Therapeutics: Nuclear factor (erythroid-derived 2)-like 2 (NFE2L2; NRF2); heme oxygenase decycling 1 (HMOX1; HO-1; Hsp32)

Cell culture and mouse studies identified two activators of the anti-inflammatory NFE2L2/HMOX1 pathway that could help treat inflammation. Chemical synthesis and hemoglobin-based assays of compounds linking diverse NFE2L2 inducers to cobalt-carbon monoxide complexes identified two compounds that released carbon monoxide - which promotes up-regulation of NFE2L2 - and exhibited low toxicity in mouse glial cells. In mouse microglial cell lines, each compound increased levels of NFE2L2 compared with vehicle. In mice, each compound increased lung and liver levels of HMOX1 and blood levels of carboxyhemoglobin. Next steps could include testing the compounds in animal models of inflammation.

Biogen Inc. markets the NFE2L2 pathway activator Tecfidera dimethyl fumarate to treat multiple sclerosis (MS)...