Pharmacological Chaperones as Potential Therapeutics for Lysosomal Storage Disorders: Preclinical Research to Clinical Studies

Boyd, Robert E.; Elias, Benjamin; Xu, Su; Khanna, Richie; Valenzano, Kenneth J.

doi:10.1002/9781118978320.ch15

Cited by 2 publications

(1 citation statement)

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“…These strategies range from traditional enzyme replacement therapy alternatives to novel biotechnological tools such as CRISPR/Cas9 and prime editing, with promising results in both in vitro and in vivo models. Although some of these developments have been translated to clinical trials [96][97][98][99], there is not an approved and effective treatment for TSD, SD, or AB variant yet. In this section, we review the current proposals and advances in therapeutics for GM2 gangliosidosis.…”

Section: Current Proposals For the Treatment Of Gm2 Gangliosidosismentioning

confidence: 99%

GM2 Gangliosidosis: Clinical Features and Current Therapies

Leal¹,

Benincore-Flórez²,

Solano-Galarza³

et al. 2020

Preprint

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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.

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Section: Current Proposals For the Treatment Of Gm2 Gangliosidosismentioning

confidence: 99%