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Open AccessArticle

Conventional and Unconventional Therapeutic Strategies for Sialidosis Type I

1
Department of Genetics, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA
2
Department of Anatomy and Neurobiology, College of Graduate Health Sciences, University of Tennessee Health Science Center, Memphis, TN 38163, USA
3
Ultragenyx Pharmaceutical, Novato, CA 94949, USA
4
Office of the Clinical Director & Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health (NHGRI), Bethesda, MD 20892, USA
5
Undiagnosed Disease Network, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA
6
Unit of Genetics of Neurodegenerative and Metabolic Diseases, Fondazione IRCCS Istituto Neurologico Carlo Besta, 20133 Milan, Italy
7
Neurophysiopathology, Fondazione IRCCS Istituto Neurologico Carlo Besta, 20133 Milan, Italy
8
Department of Metabolic Diseases, Wilhelmina Children’s Hospital, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
J. Clin. Med. 2020, 9(3), 695; https://doi.org/10.3390/jcm9030695
Received: 1 February 2020 / Revised: 26 February 2020 / Accepted: 27 February 2020 / Published: 4 March 2020
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 oligosacchariduria. Overall these findings suggest that carefully balanced, unconventional dietary compounds in combination with conventional therapeutic approaches may prove to be beneficial for the treatment of sialidosis type I. View Full-Text
Keywords: sialidosis type I; NEU1; PPCA; dietary and pharmacological compounds; therapy sialidosis type I; NEU1; PPCA; dietary and pharmacological compounds; therapy
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MDPI and ACS Style

Mosca, R.; van de Vlekkert, D.; Campos, Y.; Fremuth, L.E.; Cadaoas, J.; Koppaka, V.; Kakkis, E.; Tifft, C.; Toro, C.; Allievi, S.; Gellera, C.; Canafoglia, L.; Visser, G.; Annunziata, I.; d’Azzo, A. Conventional and Unconventional Therapeutic Strategies for Sialidosis Type I. J. Clin. Med. 2020, 9, 695. https://doi.org/10.3390/jcm9030695

AMA Style

Mosca R, van de Vlekkert D, Campos Y, Fremuth LE, Cadaoas J, Koppaka V, Kakkis E, Tifft C, Toro C, Allievi S, Gellera C, Canafoglia L, Visser G, Annunziata I, d’Azzo A. Conventional and Unconventional Therapeutic Strategies for Sialidosis Type I. Journal of Clinical Medicine. 2020; 9(3):695. https://doi.org/10.3390/jcm9030695

Chicago/Turabian Style

Mosca, Rosario; van de Vlekkert, Diantha; Campos, Yvan; Fremuth, Leigh E.; Cadaoas, Jaclyn; Koppaka, Vish; Kakkis, Emil; Tifft, Cynthia; Toro, Camilo; Allievi, Simona; Gellera, Cinzia; Canafoglia, Laura; Visser, Gepke; Annunziata, Ida; d’Azzo, Alessandra. 2020. "Conventional and Unconventional Therapeutic Strategies for Sialidosis Type I" J. Clin. Med. 9, no. 3: 695. https://doi.org/10.3390/jcm9030695

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