First author Nol Derecki and his colleagues began their work with male Rett mouse models, which lack any Mecp2. These Mecp2-null mice mimic the human disorder, with neurological symptoms beginning to appear at about 4 weeks of age and an approximate life expectancy of only 8 weeks. Radiation treatment was administered at 4 weeks, followed by a bone marrow transplant from normal (wild-type) mice. As engraftment - the migration and repopulation of new microglia - took place, the Rett mice began to grow instead of fail. Body and brain sizes approached those of wild-type mice, gait improved and mobility increased significantly. There were no signs of the severe tremors seen in untreated mice. Apneas and other breathing irregularities were markedly diminished. The oldest of these mice is now almost a year. Work with female Rett mouse models at more advanced stages of disease is currently underway.
Gail Mandel, Ph.D., whose Rett research focuses on astrocytes, another type of glial cell impaired by mutations in MECP2, comments, "A fascinating aspect of these findings is the data suggesting that deficits in the engulfing properties of microglia are a crucial aspect of Rett neuropathology. It will now be necessary to develop cellular assays to determine all the ways these immune cells are bolstering neuronal functions and whether they can be therapeutically harnessed." Dr. Mandel is a Senior Scientist at the V
|Contact: Monica Coenraads|
Rett Syndrome Research Trust