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: S Martino, C Cavalieri, C Emiliani, D Dolcetta, M G Cusella De Angelis, V Chigorno, G M Severini, K Sandhoff, C Bordignon, S Sonnino, A Orlacchio
• Journal: Neurochemical research (Neurochem Res) Vol. 27 Issue 7-8 Pg. 793-800 (Aug 2002) ISSN: 0364-3190 [Print] United States
• PMID: 12374215 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• G(M2) Ganglioside

Topics

• Animals
• Bone Marrow Cells (metabolism)
• Chromatography, Thin Layer
• G(M2) Ganglioside (metabolism)
• Genetic Vectors
• Mice
• Models, Animal
• Retroviridae (genetics)
• Stromal Cells (metabolism)
• Tay-Sachs Disease (metabolism)