Globoid cell leukodystrophy (GLD), or Krabbe disease, is an inherited, 
neurologic disorder that results from deficiency of a lysosomal enzyme, 
galactosylceramidase. Most commonly, deficits of galactosylceramidase result in 
widespread central and peripheral nervous system demyelination and death in 
affected infants typically by 2 years of age. Hematopoietic stem-cell 
transplantation is the current standard of care in children diagnosed prior to 
symptom onset. However, disease correction is incomplete. Herein, the first 
adeno-associated virus (AAV) gene therapy experiments are presented in a 
naturally occurring canine model of GLD that closely recapitulates the clinical 
disease progression, neuropathological alterations, and biochemical 
abnormalities observed in human patients. Adapted from studies in twitcher mice, 
GLD dogs were treated by combination intravenous and intracerebroventricular 
injections of AAVrh10 to target both the peripheral and central nervous systems. 
Combination of intravenous and intracerebroventricular AAV gene therapy had a 
clear dose response and resulted in delayed onset of clinical signs, extended 
life-span, correction of biochemical defects, and attenuation of neuropathology. 
For the first time, therapeutic effect has been established in the canine model 
of GLD by targeting both peripheral and central nervous system impairments with 
potential clinical implications for GLD patients.