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Review
. 2024 Apr 26:18:1392683.
doi: 10.3389/fnins.2024.1392683. eCollection 2024.

Therapeutic developments for neurodegenerative GM1 gangliosidosis

Dorian Foster  1 , Lucian Williams  2 , Noah Arnold  1 , Jessica Larsen  1   2
Affiliations
Review

Therapeutic developments for neurodegenerative GM1 gangliosidosis

Dorian Foster et al. Front Neurosci. .

Abstract

GM1 gangliosidosis (GM1) is a rare but fatal neurodegenerative disease caused by dysfunction or lack of production of lysosomal enzyme, β-galactosidase, leading to accumulation of substrates. The most promising treatments for GM1, include enzyme replacement therapy (ERT), substrate reduction therapy (SRT), stem cell therapy and gene editing. However, effectiveness is limited for neuropathic GM1 due to the restrictive nature of the blood-brain barrier (BBB). ERT and SRT alleviate substrate accumulation through exogenous supplementation over the patient's lifetime, while gene editing could be curative, fixing the causative gene, GLB1, to enable endogenous enzyme activity. Stem cell therapy can be a combination of both, with ex vivo gene editing of cells to cause the production of enzymes. These approaches require special considerations for brain delivery, which has led to novel formulations. A few therapeutic interventions have progressed to early-phase clinical trials, presenting a bright outlook for improved clinical management for GM1.

Keywords: GM1 gangliosidosis; clinical trials; enzyme replacement therapy; gene therapy; lysosomal storage disease; neurodegeneration; substrate reduction therapy.

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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
Treatment approaches currently being studied in pre-clinical and clinical settings for neuropathic lysosomal storage disorder GM1 gangliosidosis. Created with Biorender.
See this image and copyright information in PMC

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