Overview

• Stanford Medicine researchers combined targeted brain irradiation, microglia-depleting drugs and immunosuppression to introduce non-matched donor microglial precursors directly into mouse brains.
• Donor cells made up more than 85% of brain microglia eight months after transplantation, demonstrating long-lasting engraftment in treated animals.
• Sandhoff disease mice treated with the therapy survived up to 250 days compared with a median of 135 days in untreated controls and displayed improved motor skills and exploration.
• The transplanted microglia produced the missing lysosomal enzyme that was detected in native neurons, suggesting intercellular enzyme transfer underlies the therapeutic effect.
• By avoiding systemic preconditioning toxicity and graft-versus-host reactions, the approach is positioned for human translation and potential use in Alzheimer’s and other neurodegenerative diseases.