Neuroimmunology in globoid cell leukodystrophy: A comprehensive review including treatments, models, and neuroimmune mechanisms underlying neuropathology.

Globoid cell leukodystrophy (GLD), or Krabbe's disease, is a fatal genetic demyelinating disease of the central nervous system (CNS) caused by loss-of-function mutations in galactosylceramidase (GALC). As a result of the loss of GALC enzymatic activity, there is an accumulation of a toxic lipid called galactosylsphingosine, or psychosine. Current treatments have focused on restoring GALC function as a means to reduce psychosine accumulation, which show promise, however, still have limited success at improving behavioral or cognitive deficits in infants with GLD. Recent studies have discovered a role for T cells in GLD, indicating that there is a previously understudied role for the adaptive immune system as a contributing factor to GLD pathophysiology. This review aims to provide a comprehensive discussion of the current field of GLD research including treatment advances and GLD pathophysiology, with a focus on the role of neuroimmunological mechanisms contributing to GLD.