Researchers have used bone marrow transplants to halt the symptoms of Rett syndrome, an autism-spectrum disorder, in mice. Conducted by Noël C. Derecki and colleagues at the University of Virginia School of Medicine, the study suggests that bone marrow transplantation may offer a potential treatment for humans with Rett syndrome, which is typically deadly in boys and debilitating in girls. The findings, reported in Nature, connect the immune system to Rett in an unexpected way. “Everything we found in the mouse models for Rett may have implications for other neurological disorders which may or may not be on the autistic spectrum,” says study leader Jonathan Kipnis. Rett syndrome is predominantly caused by the mutation of an X-chromosome gene named MECP2. It is fatal in human males, resulting in miscarriage, stillbirth, or early death. In girls, who have one normal X and one mutant X, the symptoms include seizures, uncontrollable hand clasping, difficulty walking, speech issues, and frequent apneas, during which they stop breathing. The mouse model for Rett syndrome duplicates many of the same symptoms—the mice clasp their legs, have extreme difficulty walking, and have involuntary tremors and breathing difficulties. After the research team replaced the bone marrow of male mice—with severe disease and a lifespan of only eight weeks—the mice grew stronger, gained weight, and began to walk better. The animals’ breathing improved dramatically. They also began living significantly longer, with the oldest now approaching a year of age. The researchers believe that replacing the immune system is fostering a healthier environment in the brain, improving neuron function. The study data suggest that the dramatic results are due to the repopulation of microglia, immune cells that clear debris in the brain. Unlike other brain cells, such as neurons and astroglia, microglia can be replaced, Kipnis says. “Those are immune-derived cells,” he says. “So by fixing bone marrow, you could fix the brain.” To test this hypothesis, they repeated the bone-marrow experiment, only shielding the mice’s brains from radiation. This prevented the immune system from entering the brain itself. Only the body was repopulated with immune cells. Those mice showed only slight improvement in Rett symptoms. The research is primarily funded by the Rett Syndrome Research Trust.