Scientific Results

Pre-diagnosing and managing patients with GM1 gangliosidosis and related disorders by the evaluation of GM1 ganglioside content

Year: 2019

Authors: Tonin R., Caciotti A., Procopio E., Fischetto R., Deodato F., Mancardi MM., Di Rocco M., Ardissone A., Salviati A., Marangi A., Strisciuglio P., Mangone G., Casini A., Ricci S., Fiumara A., Parini R., Pavone FS., Guerrini R., Calamai M., Morrone A.

Autors Affiliation: Meyer Childrens Hosp, Neurosci Dept, Mol & Cell Biol Lab Neurometab Dis, Florence, Italy; Meyer Childrens Hosp, Metab Unit, Florence, Italy; Osped Reg Pediat Giovanni XXIII, Div Malattie Metab Genet Med, Bari, Italy; Bambino Gesu Pediat Hosp, IRCCS, Div Metab, Rome, Italy; IRCCS Ist Giannina Gaslini, Unit Rare Dis, Genoa, Italy; Fdn IRCCS Ist Nazl Neurol C Besta, Div Neuropsichiat Infantile, Milan, Italy; Univ Verona, Dept Biotechnol, Verona, Italy; Hosp Vicenza, Neurol Unit, Vicenza, Italy; Federico II Univ Naples, Sect Pediat, Dept Translat Med Sci, Naples, Italy; Univ Florence, Dept Hlth Sci, Sect Pediat, Div Immunol, Florence, Italy; Meyer Childrens Hosp, Florence, Italy; PO Gaspare Rodolico, Malattie Metab & Sindromi Malformat Congenite, Catania, Italy; Osped San Gerardo, Clin Pediat, UOS Malattie Metab Rare, Monza, Italy; Univ Florence, European Lab Nonlinear Spect LENS, Florence, Italy; Univ Florence, Area Farmaco & Salute Bambino, Dipartimento Neurosci, Psicol, Florence, Italy; CNR, Natl Res Council Italy, Natl Inst Opt, Florence, Italy

Abstract: GM1 ganglioside, a monosialic glycosphingolipid and a crucial component of plasma membranes, accumulates in lysosomal storage disorders, primarily in GM1 gangliosidosis. The development of biomarkers for simplifying diagnosis, monitoring disease progression and evaluating drug therapies is an important objective in research into neurodegenerative lysosomal disorders. With this in mind, we established fluorescent imaging and flow-cytometric methods to track changes in GM1 ganglioside levels in patients with GM1 gangliosidosis and in control cells. We also evaluated GM1 ganglioside content in patients’ cells treated with the commercially available Miglustat, a substrate inhibitor potentially suitable for the treatment of late-onset GM1 gangliosidosis. The flow-cytometric method proved to be sensitive, unbiased, and rapid in determining variations in GM1 ganglioside content in human lymphocytes derived from small amounts of fresh blood. We detected a strong correlation between GM1 ganglioside content and the clinical severity of GM1 gangliosidosis. We confirm the ability of Miglustat to act as a substrate reduction agent in the patients’ treated cells. As well as being suitable for diagnosing and managing patients with GM1 gangliosidosis this method could be useful in the diagnosis and management of other lysosomal diseases, such as galactosialidosis, Type C Niemann-Pick, and any other disease with pathologic variations of GM1 ganglioside.

Journal/Review: SCIENTIFIC REPORTS

Volume: 9      Pages from: 17684-1  to: 17684-10

KeyWords: DISEASE TYPE-C; BETA-GALACTOSIDASE; CHOLERA-TOXIN; PHARMACOLOGICAL CHAPERONES; G(M1) GANGLIOSIDOSIS; ENZYME REPLACEMENT; LYSOSOMAL STORAGE; MOUSE MODEL; GM1-GANGLIOSIDOSIS; BIOMARKERS
DOI: 10.1038/s41598-019-53995-5

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