Restoration of the GM2 ganglioside metabolism in bone marrow-derived stromal cells from Tay-Sachs disease animal model.
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.
Martino
S
S
Dipartimento di Scienze Biochimiche e Biotecnologie Molecolari, University of Perugia, Italy.
Cavalieri
C
C
Emiliani
C
C
Dolcetta
D
D
Cusella De Angelis
M G
MG
Chigorno
V
V
Severini
G M
GM
Sandhoff
K
K
Bordignon
C
C
Sonnino
S
S
Orlacchio
A
A
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*
D005678:G(M2) Ganglioside