Microglia replacement halts the progression of microgliopathy in mice and humans

Adult onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP)/CSF1R related leukoencephalopathy

Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) is a rare neurological disorder caused by mutations in the CSF1R gene, which impairs microglia, the brain’s resident immune cells. In this study, scientists discovered a new potential way of treating ALSP. They developed special mouse models carrying the same CSF1R mutations found in people with ALSP. These mice exhibited the same brain changes as patients, including decreased microglial numbers, nerve damage, loss of myelin, and problems with memory and walking. The team then tested bone marrow transplantation (BMT) to replace the dysfunctional microglia with healthy ones. In mice, this intervention halted disease progression, improved myelination, restored brain signalling and rescued both movement and memory functions. Lastly, researchers investigated microglia replacement by BMT in 8 patients with ALSP. During the 24-month follow-up after treatment, brain scans showed improved brain metabolism (PET imaging), and the clinical symptoms stabilised instead of worsening. In conclusion, the results show that replacing damaged microglia with healthy ones can stop the progression of ALSP in both mice and humans. These findings support the use of BMT as a novel therapeutic strategy for ALSP and other neurological diseases presenting microglial dysfunction.