Abstract
CSF1R-related leukoencephalopathy is an adult-onset leukoencephalopathy with axonal spheroids and pigmented glia caused by colony stimulating factor 1 receptor (CSF1R) gene mutations. The disease has a global distribution and currently has no cure. Individuals with CSF1R-related leukoencephalopathy variably present clinical symptoms including cognitive impairment, progressive neuropsychiatric and motor symptoms. CSF1R is predominantly expressed on microglia within the central nervous system (CNS), and thus CSF1R-related leukoencephalopathy is now classified as a CNS primary microgliopathy. This urgent unmet medical need could potentially be addressed by using microglia-based immunotherapies. With the rapid recent progress in the experimental microglial research field, the replacement of an empty microglial niche following microglial depletion through either conditional genetic approaches or pharmacological therapies (CSF1R inhibitors) is being studied. Furthermore, hematopoietic stem cell transplantation offers an emerging means of exchanging dysfunctional microglia with the aim of reducing brain lesions, relieving clinical symptoms and prolonging the life of patients with CSF1R-related leukoencephalopathy. This review article introduces recent advances in microglial biology and CSF1R-related leukoencephalopathy. Potential therapeutic strategies by replacing microglia in order to improve the quality of life of CSF1R-related leukoencephalopathy patients will be presented.
Highlights
CSF1R-related leukoencephalopathy, a subgroup of adult-onset leukodystrophy, is a progressive neurodegenerative white matter disease caused by mutations in the colony stimulating factor 1 receptor (CSF1R) gene [1]
The alanyl tRNA synthetase (AARS) gene mutation has recently been identified in the original Swedish hereditary diffuse leukoencephalopathy with spheroids (HDLS) family, who have been tested for CSF1R gene mutation status with negative results [6]
We have previously demonstrated that the brain volume fractions measured by magnetic resonance imaging (MRI) did not differ significantly between CSF1R-related leukoencephalopathy and multiple sclerosis (MS) patients, while the cerebellum was relatively spared in CSF1R-related leukoencephalopathy patients [18]
Summary
CSF1R-related leukoencephalopathy, a subgroup of adult-onset leukodystrophy, is a progressive neurodegenerative white matter disease caused by mutations in the colony stimulating factor 1 receptor (CSF1R) gene [1]. The CNS-resident immune cells, are affected in this condition, developing immune cell-based therapies in order to improve disease prognosis and the quality of life of patients with CSF1R-related leukoencephalopathy represents a potential strategy to meet this urgent medical need.
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