The GM2 gangliosidoses: Unlocking the mysteries of pathogenesis and treatment

• Published in: Neuroscience letters 2021-11, Vol.764, p.136195-136195, Article 136195
• Main Authors: Toro, Camilo, Zainab, Mosufa, Tifft, Cynthia J.
• Format: Article
• Language: English
• Subjects: Age of Onset; Animals; beta-Hexosaminidase alpha Chain - genetics; beta-Hexosaminidase alpha Chain - metabolism; beta-Hexosaminidase beta Chain - genetics; beta-Hexosaminidase beta Chain - metabolism; Cerebellum - pathology; Disease Models, Animal; Enzyme Replacement Therapy - methods; G(M2) Ganglioside - antagonists & inhibitors; G(M2) Ganglioside - metabolism; Gangliosidoses; Gangliosidoses, GM2 - genetics; Gangliosidoses, GM2 - pathology; Gangliosidoses, GM2 - therapy; Gene therapy; Genetic Therapy - methods; Glucosyltransferases - antagonists & inhibitors; Glucosyltransferases - metabolism; Glycoside Hydrolase Inhibitors - pharmacology; Glycoside Hydrolase Inhibitors - therapeutic use; GM2; Gray Matter - pathology; HEXA; HEXB; Hexosaminidase A; Humans; Lysosomal storage diseases; Mutation; Retina - pathology; Sandhoff disease; Spinal Cord - pathology; Tay-Sachs disease; White Matter - pathology
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/j.neulet.2021.136195

•GM2 gangliosidoses are a disease continuum dependent on residual enzyme activity.•Developmental and degenerative events are part of Infantile GM2 gangliosidoses.•Infantile GM2 gangliosidoses targets gray matter, white matter, and the retina.•Late-onset GM2 gangliosidoses targets preferentially the spinal cord and cerebellum.•Late-onset GM2 gangliosidoses has features akin to other neurodegenerative diseases.•Animal and cell-based GM2 gangliosidoses models inform biology and therapeutics.•Some clinical features may distinguishing late-onset Tay-Sachs from Sandhoff disease.•Impact of future therapies depends on pre-treatment disease burden.•The time from symptom onset to molecular diagnosis remains unacceptably protracted.