Guillain-Barré syndrome: Novel treatment by complement inhibition

Abstract

Guillain-Barré syndrome (GBS) is an immune-mediated polyneuropathy that can cause acute flaccid tetraparesis and respiratory failure. Intravenous immunoglobulin and plasmapheresis were established as a standard of care, but 20% to 30% of patients require mechanical ventilation during the acute phase and up to 20% of patients cannot walk independently even 1 year after the onset. As the pathophysiology of GBS has been elucidated, complement activation draws attention as a key treatment point. In acute motor axonal neuropathy, anti-ganglioside antibody deposition and resulting complement activation lead to nerve conduction failure and eventually axonal degeneration. In acute inflammatory demyelinating polyneuropathy, although the process has not been clearly revealed, autopsied specimens showed that terminal complement complex rimmed the surface of the Schwann cells. Eculizumab is an antibody to the complement protein C5 and can potently inhibit complement activation. In a murine model with anti-ganglioside antibody–mediated neuropathy, eculizumab can avert respiratory failure and motor neuropathy. A randomized controlled phase II trial showed that eculizumab might be effective also for GBS patients. Inhibition of complement activation can be a new therapeutic option in the near future.