Bruton Tyrosine Kinase Inhibition in Autoimmune Demyelinating Disorders

Bruton Tyrosine Kinase (BTK) is a cytoplasmic enzyme critical to signal transduction in both B lymphocytes and myeloid cells, including microglia and macrophages. In autoimmune demyelinating disorders such as multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD), dysregulated activation of these immune populations drives chronic inflammation, demyelination and axonal injury. Small-molecule BTK inhibitors, administered orally, penetrate the central nervous system and selectively attenuate pathogenic B-cell receptor and Fc receptor signalling without broad immunodepletion. Beyond dampening autoantibody production and antigen presentation, BTK blockade modulates microglial phenotype, reduces pro-inflammatory cytokine release, enhances myelin debris clearance and fosters remyelination. Emerging clinical data suggest that next-generation BTK inhibitors may slow disease progression in relapsing and progressive forms of MS, offering an innovative therapeutic approach that bridges immunomodulation with neuroprotective repair mechanisms.

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Bruton Tyrosine Kinase Inhibition in Autoimmune Demyelinating Disorders publication trend

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Technical terms

Bruton Tyrosine Kinase (BTK): A cytoplasmic enzyme that transmits activation signals from B-cell receptors and Fc receptors on myeloid cells.

Demyelination: The loss or damage of the myelin sheath insulating nerve fibres in the central nervous system.

Microglia: Resident immune cells of the central nervous system that mediate inflammatory responses and tissue repair.

Remyelination: The restoration of damaged myelin sheaths by oligodendrocytes or recruited precursor cells.

Experimental Autoimmune Encephalomyelitis (EAE): An animal model that mimics key immunological and neuropathological features of multiple sclerosis.

References

1. BTK inhibition limits microglia-perpetuated CNS inflammation and promotes myelin repair. Acta Neuropathologica (2024).
2. Bruton’s tyrosine kinase-bearing B cells and microglia in neuromyelitis optica spectrum disorder. Journal of Neuroinflammation (2023).
3. Remibrutinib (LOU064) inhibits neuroinflammation driven by B cells and myeloid cells in preclinical models of multiple sclerosis. Journal of Neuroinflammation (2023).