Preprint Review Version 2 Preserved in Portico This version is not peer-reviewed

GM2 Gangliosidoses: Clinical Features, Pathophysiological Aspects and Current Therapies

Version 1 : Received: 6 July 2020 / Approved: 7 July 2020 / Online: 7 July 2020 (17:35:24 CEST)
Version 2 : Received: 3 August 2020 / Approved: 5 August 2020 / Online: 5 August 2020 (05:05:13 CEST)

A peer-reviewed article of this Preprint also exists.

Leal, A.F.; Benincore-Flórez, E.; Solano-Galarza, D.; Garzón Jaramillo, R.G.; Echeverri-Peña, O.Y.; Suarez, D.A.; Alméciga-Díaz, C.J.; Espejo-Mojica, A.J. GM2 Gangliosidoses: Clinical Features, Pathophysiological Aspects, and Current Therapies. Int. J. Mol. Sci. 2020, 21, 6213. Leal, A.F.; Benincore-Flórez, E.; Solano-Galarza, D.; Garzón Jaramillo, R.G.; Echeverri-Peña, O.Y.; Suarez, D.A.; Alméciga-Díaz, C.J.; Espejo-Mojica, A.J. GM2 Gangliosidoses: Clinical Features, Pathophysiological Aspects, and Current Therapies. Int. J. Mol. Sci. 2020, 21, 6213.

Journal reference: Int. J. Mol. Sci. 2020, 21, 6213
DOI: 10.3390/ijms21176213

Abstract

GM2 gangliosidoses are a group of pathologies characterized by GM2 ganglioside accumulation into the lysosome due to mutations on the genes encoding for the β-hexosaminidases subunits or the GM2 activator protein. Three GM2 gangliosidoses have been described: Tay-Sachs disease, Sandhoff disease, and the AB variant. Central nervous system dysfunction is the main characteristic of GM2 gangliosidoses patients that include neurodevelopment alterations, neuroinflammation, and neuronal apoptosis. Currently, there is not approved therapy for GM2 gangliosidoses, but different therapeutic strategies have been studied including hematopoietic stem cell transplantation, enzyme replacement therapy, substrate reduction therapy, pharmacological chaperones, and gene therapy. The blood-brain barrier represents a challenge for the development of therapeutic agents for these disorders. In this sense, alternative routes of administration (e.g. intrathecal or intracerebroventricular) have been evaluated, as well as the design of fusion peptides that allow the protein transport from the brain capillaries to the central nervous system. In this review, we outline the current knowledge about clinical and physiopathological findings of GM2 gangliosidoses, as well as the ongoing proposals to overcome some limitations of the traditional alternatives by using novel strategies such as molecular Trojan horses or advanced tools of genome editing.

Subject Areas

Lysosomal Storage Disorders; GM2 gangliosidoses; Tay-Sachs disease; Sandhoff disease; β-Hexosaminidases; Therapeutic alternatives

Comments (1)

Comment 1
Received: 5 August 2020
Commenter: Carlos Alméciga-Díaz
Commenter's Conflict of Interests: Author
Comment: We performed an English revision and updated the references.
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