Yoshikatsu Eto
Department
of Pediatrics / Department of Gene Therapy, Institute for DNA Medicine, Tokyo
Jikei University School of Medicine, Tokyo, Japan
Among various
genetic disorders, we focused to lysosomal storage disease (LSD) which are
caused by a genetic deficiency of lysosomal enzyme and accumulates various
compounds in lysosomes. Recently, LSD patients can be treated by 1) Enzyme
replacement therapy in Gaucher disease, Fabry disease, Hunter syndrome, Pompe
disease, Hurler syndrome. The ERT is limited to treat in non-neurological form
of LSD. 2) Bone marrow transplantation (BMT) is also potentially important
therapy to treat LSD, since BMT may treat neurological involvement of LSD, if
treated in early period. 3) Cell therapy/Gene therapy are most promising
treatment for LSD in future. We are trying to treat LSD using MPS VII, Sly
mice. And twitcher mice (model for human Krabbe disease). Using these model
mice, we tried to treat these mice with adenovirus vector by intravenous
administration or intraventricular administration. Visceral involvement in Sly
mice was successfully treated by adenovirus administration at least for 1
month. In twitcher mice, intraventricular administration of adenovirus showed
reduced number of globoid cells in CNS, which indicated that the CNS
involvement could be treated with gene therapy. Many LSD patients show
neurological disorders, since these cells can be converted into neuronal cells
in a certain condition. These results suggest that mesenchymal cells can be
used for the treatment of CNS involvement in LSD.