Abstract
Krabbe Disease (KD) is an autosomal metabolic disorder that affects both the central and peripheral nervous systems. It is caused by a functional deficiency of the lysosomal enzyme, galactocerebrosidase (GALC), resulting in an accumulation of the toxic metabolite, psychosine. Psychosine accumulation affects many different cellular pathways, leading to severe demyelination. Although there is currently no effective therapy for Krabbe disease, recent gene therapy-based approaches in animal models have indicated a promising outlook for clinical treatment. This review highlights recent findings in the pathogenesis of Krabbe disease, and evaluates AAV-based gene therapy as a promising strategy for treating this devastating pediatric disease.
Highlights
Reviewed by: Pasqualina Colella, Stanford University, United States Vasco Meneghini, San Raffaele Telethon Institute for Gene Therapy (SR-Tiget), Italy
This review describes recent findings that provide insights into pathological mechanisms of Krabbe Disease (KD) and evaluates therapeutic avenues far explored in treating KD, with a focus on associated viral vectors (AAV)-based gene therapies
The psychosine hypothesis was proposed nearly 50 years ago and states that a loss in GALC activity leads to psychosine accumulation, which in turn causes the neural pathology seen in KD [58]
Summary
Krabbe Disease (KD) is an autosomal metabolic disorder that affects both the central and peripheral nervous systems. It is caused by a functional deficiency of the lysosomal enzyme, galactocerebrosidase (GALC), resulting in an accumulation of the toxic metabolite, psychosine. This review highlights recent findings in the pathogenesis of Krabbe disease, and evaluates AAV-based gene therapy as a promising strategy for treating this devastating pediatric disease. Krabbe Disease (KD) is a devastating pediatric lysosomal storage disorder that affects both the central and peripheral nervous systems. It was first described in detail in 1916 by a Danish neurologist, Knud Krabbe who lends his name to the disease [1].
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