Therapeutics: Nuclear factor (erythroid-derived 2)-like 2 (NFE2L2; NRF2)

Patient sample, cell culture and mouse studies suggest promoting NFE2L2 activity could help treat Hutchinson-Gilford progeria syndrome (HGPS). In patient fibroblasts, NFE2L2 activity was lower than in fibroblasts from healthy volunteers. Also in patient fibroblasts, a plasmid encoding constitutively active NFE2L2 decreased reactive oxygen species (ROS) levels and the rate of aberrant nuclear morphological changes - a hallmark of progeria - compared with vehicle. In mice grafted with patient-derived mesenchymal stem cells (MSCs) to model HGPS, expression of constitutively active NFE2L2 in MSCs or the NFE2L2 activator oltipraz decreased the rate of aberrant nuclear morphological changes and MSC apoptosis compared with unmodified NFE2L2 expression or vehicle. Next steps could include testing and optimizing NFE2L2 activators in animal models of HGPS.

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