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AssigneeAlbert Einstein College of Medicine
InventorsJean M. Hebert, Marta Gronska-Peski, Hiroko Nobuta
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A method of replacing endogenous microglia of a subject's brain, e.g., an adult subject, with transplanted donor microglia includes depleting at least a portion of the endogenous microglia by administering to the subject a Colony Stimulating Factor 1 Receptor (CSFR1) inhibitor, wherein the CSFR1 inhibitor is blood-brain barrier permeable and pharmacologically ablates endogenous microglia; optionally stopping administration of the CSFR1 inhibitor for a time sufficient to prevent ablation of the transplanted donor microglia; and transplanting the donor microglia into the brain of the subject to provide the transplanted donor microglia.
A method of preparing ablation-resistant donor microglia, comprising engineering donor microglia to express a constitutively active variant Colony Stimulating Factor 1 Receptor (variant CSF1R) that is resistant to a CSF1R inhibitor and providing ablation-resistant donor microglia, wherein the CSF1R inhibitor is PLX5622 and wherein the constitutively active variant CSF1R is selected from the group consisting of CSF1RL301S, CSF1RY571D, CSF1RY969F, or CSF1Rdelta706-712.
Dependencies are inferred from the claim text.