title: Restoration of the GM2 ganglioside metabolism in bone marrow-derived stromal cells from Tay-Sachs disease animal model.
abstract: The therapeutic potential of bone marrow-derived stromal cells for the therapy of Tay-Sachs disease is primarily related to the restoration of their own GM2 ganglioside storage. With this aim, we produced bone marrow-derived stromal cells from the adult Tay-Sachs animal model and transduced them with a retroviral vector encoding for the alpha-subunit of the lysosomal enzyme beta-hexosaminidase A (E.C. 3.2.1.52). Our results demonstrate that transduced Tay-Sachs bone marrow-derived stromal cells have beta-hexosaminidase A comparable to that of bone marrow-derived stromal cells from wild-type mice. Moreover, beta-hexosaminidase A in transduced Tay-Sachs bone marrow-derived stromal cells was able to hydrolyze the GM2 ganglioside in a feeding experiment, thus demonstrating the correction of the altered phenotype.
authors.affiliation: Dipartimento di Scienze Biochimiche e Biotecnologie Molecolari, University of Perugia, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Martino
authors.forename: C
authors.initials: C
authors.lastname: Cavalieri
authors.forename: C
authors.initials: C
authors.lastname: Emiliani
authors.forename: D
authors.initials: D
authors.lastname: Dolcetta
authors.forename: M G
authors.initials: MG
authors.lastname: Cusella De Angelis
authors.forename: V
authors.initials: V
authors.lastname: Chigorno
authors.forename: G M
authors.initials: GM
authors.lastname: Severini
authors.forename: K
authors.initials: K
authors.lastname: Sandhoff
authors.forename: C
authors.initials: C
authors.lastname: Bordignon
authors.forename: S
authors.initials: S
authors.lastname: Sonnino
authors.forename: A
authors.initials: A
authors.lastname: Orlacchio
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism*; D002855:Chromatography, Thin Layer; D005678:G(M2) Ganglioside / Q000378:metabolism*; D005822:Genetic Vectors; D051379:Mice; D023421:Models, Animal; D012190:Retroviridae / Q000235:genetics; D017154:Stromal Cells / Q000378:metabolism*; D013661:Tay-Sachs Disease / Q000378:metabolism*
chemical_list: D005678:G(M2) Ganglioside