Microglia replacement halts rare brain disease progression
Leukoencephalopathy for adults with axonal spheroids and pigmented glie (ALSP) is a fatal cerebral disease caused by a mutation in a copy of the gene coding for the factor 1 receptor stimulating the colonies (CSF1R), which is mainly expressed in microglia. However, there is little to know about pathology due to a lack of appropriate mouse models. In an article in ScienceWu et al. Introduce two models of mice hosting changes in hotspot in humans CSF1R who closely imitate the ALSP phenotype, with less microglies, cerebral calcification, myelin pathology, axonal swelling and spheroids. They then explored if the replacement of microglia transferred by healthy microglies could be an effective treatment strategy.
The authors first tested a previously developed strategy which exhausted microglia by the inhibition of the CSF1R, then replaced them by transplantation of bone marrow. This treatment saved the transduction of the neuronal signal and improved the cognitive and motor function. In the case of CSF1R-Microglia deficient in Alsp, the authors estimated that the exhaustion of microglies may not be necessary. Indeed, a traditional bone marrow transplant had similar therapeutic effects.
