Transplantation Therapy in a Mouse Model of Rett Syndrome

RESEARCH HIGHLIGHTS Nature Reviews Neurology 8, 239 (2012); published online 10 April 2012; doi:10.1038/nrneurol.2012.65 NEURODEVELOPMENTAL DISORDERS Transplantation therapy in a mouse model of Rett syndrome Transplantation of bone marrow observed when functional microglial cell cells might offer a new approach to populations in the brain parenchyma were the treatment of Rett syndrome, an repopulated by the transplanted cells. X-linked autism spectrum disorder The Mecp2-null male mice were caused by mutations in the MECP2 gene. irradiation-conditioned prior to Researchers at the University of transplantation, to promote engraftment Virginia, USA, have demonstrated that of the microglia-like cells that ameliorate transplantation of wild-type bone marrow the disease process. In mice that were into Mecp2-null male mice brought about head-covered to prevent irradiation of increased lifespan, a normalized breathing brain parenchyma, no engraftment or pattern, reduced apnoea episodes, and arrest of disease pathology occurred. The increased body weight and locomotor researchers also demonstrated that targeted activity. Similar benefits were also expression of Mecp2 in myeloid cells +/– observed in female Mecp2 mice, which attenuated the Rett disease process in mice. Microglia-like cells (green) invading brain tissue and develop a milder form of the disease. Blockade of the phagocytic activity of interacting with Purkinje cells (red). Image courtesy of The researchers initially expected T cells microglial cells—by using annexin V to James Cronk (Kipnis laboratory). to have a protective role in Rett syndrome. mask crucial phosphatidylserine residues want to see whether immune therapies As Jonathan Kipnis, who led the study, on apoptotic cells—also diminished could reverse as well as arrest the disease, explains: “we previously showed that the beneficial effects associated with and we are trying to find approaches elimination of T cells results in impaired expression of wild-type protein in that would boost the immune activity of cognitive function in mice, along with myeloid cells. “We would like to better myeloid cells in Rett patients,” he explains. reduced synaptogenesis and reduced levels understand the phagocytic role of Ellen Bible of brain-derived neurotrophic factor. Rett microglia in Rett syndrome and other syndrome possesses some of the aspects autism spectrum disorders,” Kipnis Original article Derecki, N. C. et al. Wild-type microglia that we see also in immune-deficient comments. Moreover, the results of their arrest pathology in a mouse model of Rett syndrome. mice.” However, their observations instead study suggest that modulation of the Nature doi:10.1038/nature10907 highlighted a key role for microglial immune response could be a potential Further reading Lioy, D. T. et al. A role for glia in the cells in Rett syndrome, as beneficial new therapeutic avenue for patients with progression of Rett’s syndrome. Nature doi:10.1038/ nature10214 effects on the disease process were only some neurodevelopmental disorders. “We NATURE REVIEWS | NEUROLOGY VOLUME 8 | MAY 2012 © 2012 Macmillan Publishers Limited. All rights reserved.

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