The path to clinical application of human microglia transplantation for the treatment of CSF1R-Related disorder

INTRODUCTION: Colony Stimulating Factor 1 Receptor (CSF1R)-Related Disorder (CSF1R-RD) is a rare, rapidly progressive hereditary neurodegenerative microgliopathy caused by pathogenic variants in the CSF1R gene, leading to dysfunctional microglia. The disease presents with diverse, progressive neurological symptoms, including motor and cognitive decline, and has a poor prognosis. AREA COVERED: This review critically examines the emerging therapeutic landscape for CSF1R-RD, with a primary focus on the disease-modifying potential of Hematopoietic Stem Cell Transplantation (HSCT). It synthesizes data from cohort studies and case reports, analyzing outcomes, neuroradiological changes, and the safety profile of HSCT. Furthermore, the review discusses the utility of advanced neuroimaging and fluid biomarkers, such as Neurofilament light chain (NfL) and Glial fibrillary acidic protein (GFAP), which are crucial for monitoring disease progression and evaluating therapeutic response. EXPERT OPINION: Growing evidence supports HSCT as a disease-modifying strategy that can stabilize or slow progression, particularly when performed early in the symptomatic phase. However, HSCT's invasiveness and associated risks highlight the need for safer, more targeted interventions. The future of CSF1R-RD treatment lies in developing less invasive microglia replacement methods and enhancing engraftment efficacy, leveraging newly established clinical and biomarker tools for precise monitoring.