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Review
. 2022 Jul 5:13:906647.
doi: 10.3389/fphar.2022.906647. eCollection 2022.

Therapeutic Strategies For Tay-Sachs Disease

Jaqueline A Picache  1 , Wei Zheng  1 , Catherine Z Chen  1
Affiliations
Review

Therapeutic Strategies For Tay-Sachs Disease

Jaqueline A Picache et al. Front Pharmacol. .

Abstract

Tay-Sachs disease (TSD) is an autosomal recessive disease that features progressive neurodegenerative presentations. It affects one in 100,000 live births. Currently, there is no approved therapy or cure. This review summarizes multiple drug development strategies for TSD, including enzyme replacement therapy, pharmaceutical chaperone therapy, substrate reduction therapy, gene therapy, and hematopoietic stem cell replacement therapy. In vitro and in vivo systems are described to assess the efficacy of the aforementioned therapeutic strategies. Furthermore, we discuss using MALDI mass spectrometry to perform a high throughput screen of compound libraries. This enables discovery of compounds that reduce GM2 and can lead to further development of a TSD therapy.

Keywords: drug development; enzymatic assay; high throughput screen (HTS); mass spectrometry; phenotypic screen; tay-sachs disease (TSD).

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
GM2 Ganglioside and HexA (A) Structure of GM2 ganglioside. Cleavage site of GM2 into GM3 via HexA is shown in red. (B) HexA isoenzyme with alpha subunit (orange) and beta subunit (yellow).
FIGURE 2
FIGURE 2
(A) Drug Development Progression. Pipeline of drug development with TSD specific assays and models. (B) Cell-based Assays for TSD. SRT: substrate reduction therapy, PC: pharmacological chaperone, ASO: antisense oligonucleotide, AAV: adeno-associated virus for gene therapy.
FIGURE 3
FIGURE 3
General workflow for performing HTS. Fibroblasts are reprogrammed into iPSCs which are programmed into NSCs. HTS is done using NSCs and MS.
See this image and copyright information in PMC

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