Replacing microglia to treat a brain disease

Microglia, the brain’s resident macrophages, are essential for maintaining central nervous system homeostasis and orchestrating immune responses. Intrinsic microglial dysfunction can lead to a group of disorders known as primary microgliopathies. A prominent example is adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP), a fatal neurological disease caused by mutations in the colony-stimulating factor 1 receptor gene (CSF1R), which is critical for microglial development and survival (1). The genetic basis of ALSP was identified more than a decade ago, but effective therapeutic strategies targeting its root cause have remained elusive (1). On page 145 of this issue, Wu et al. (2) report that replacing microglia containing the CSF1R mutation with wild-type bone marrow–derived cells can arrest disease progression in ALSP mouse models and human patients, underscoring the therapeutic promise of microglial replacement therapy.