Neurology

Patient sample and mouse studies suggest depleting microglia with CSF1R inhibitors could help treat chemotherapy-induced neurological dysfunction. In postmortem frontal lobe tissue samples from pediatric and young adult patients treated with methotrexate and other chemotherapies, the number of oligodendrocyte precursor cells (OPCs) was lower than in tissue from age-matched subjects with no history of chemotherapy. In brain tissue from a mouse model of methotrexate-induced neurological dysfunction, the number of mature OPCs and myelination levels were lower and the number of activated microglia was higher than in brain tissue from normal mice. Also in the model, PLX5622, an inhibitor of the microglia survival factor CSF1R, decreased the number of microglia in the brain and behavioral deficits and increased the number of mature OPCs and myelination levels in the white matter compared with no treatment. Next steps could include testing PLX5622 and other CSF1R inhibitors in animals exposed to other chemotherapies.

Daiichi Sankyo Co. Ltd. has PLX5622 in Phase I testing for rheumatoid arthritis (RA)...