Replacing brain immune cells in a Sandhoff disease mouse model shows immune cell enzyme is needed for neuron health

Microglial replacement in a mouse model of Sandhoff disease improves neuronal health by restoring β-hexosaminidase activity and reversing neurodegenerative changes.

• β-hexosaminidase, secreted by microglia, integrates into the lysosomes of neurons.
• Treatment with bone marrow transplant and receptor inhibition replaces deficient microglia with healthy cells.
• Replacement of microglia reverses gene signatures associated with cell death.
• Behavioral improvements are observed alongside restored enzymatic activity and expression of β-hexosaminidase.
• The intervention prevents the accumulation of toxic substrates and normalizes lysosomal function in neurons.

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