Conventional and Unconventional Therapeutic Strategies for Sialidosis Type I

Journal of Clinical Medicine
Rosario MoscaAlessandra d'Azzo

Abstract

Congenital deficiency of the lysosomal sialidase neuraminidase 1 (NEU1) causes the lysosomal storage disease, sialidosis, characterized by impaired processing/degradation of sialo-glycoproteins and sialo-oligosaccharides, and accumulation of sialylated metabolites in tissues and body fluids. Sialidosis is considered an ultra-rare clinical condition and falls into the category of the so-called orphan diseases, for which no therapy is currently available. In this study we aimed to identify potential therapeutic modalities, targeting primarily patients affected by type I sialidosis, the attenuated form of the disease. We tested the beneficial effects of a recombinant protective protein/cathepsin A (PPCA), the natural chaperone of NEU1, as well as pharmacological and dietary compounds on the residual activity of mutant NEU1 in a cohort of patients' primary fibroblasts. We observed a small, but consistent increase in NEU1 activity, following administration of all therapeutic agents in most of the fibroblasts tested. Interestingly, dietary supplementation of betaine, a natural amino acid derivative, in mouse models with residual NEU1 activity mimicking type I sialidosis, increased the levels of mutant NEU1 and resolved the oligosacch...Continue Reading

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Citations

Aug 6, 2020·The British Journal of Ophthalmology·Malena Daich VarelaEdmond J FitzGibbon
Jan 12, 2021·Molecular Therapy. Methods & Clinical Development·Jaclyn CadaoasAlessandra d'Azzo

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Methods Mentioned

BETA
electrophoresis
PCR
histone acetylation

Software Mentioned

Image Lab

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