Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

GM2 Gangliosidosis: Clinical Features and Current Therapies

Andres Felipe Leal
ORCID logo ,
Eliana Benincore-Flórez
,
Daniela Solano-Galarza
,
Rafael Guillermo Garzón Jaramillo
ORCID logo ,
Olga Yaneth Echeverri-Peña
,
Diego A. Suarez
,
Carlos Alméciga-Díaz
* ORCID logo ,
Angela Johana Espejo-Mojica
* ORCID logo
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.

Abstract

GM2 gangliosidosis 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 gangliosidosis have been described: Tay-Sachs disease, Sandhoff disease, and AB variant. Central nervous system dysfunction is the main characteristic of GM2 gangliosidosis patients that include neurodevelopment alterations, neuroinflammation, and neuronal apoptosis. Currently, there is not approved therapy for GM2 gangliosidosis, 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 gangliosidosis, 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.

Keywords

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

Subject

Medicine and Pharmacology, Pathology and Pathobiology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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