Science News from research organizations Boosting a key brain protein could help treat Rett syndrome A new gene-targeting strategy that boosts a critical brain protein may offer a future path toward treating Rett syndrome. Date: March 6, 2026 Source: Texas Children's Hospital Summary: Researchers have discovered a new way to increase a key brain protein damaged in Rett syndrome, a rare genetic disorder that affects thousands of children worldwide. Early studies in mice and patient-derived cells show the approach can restore normal brain cell function, raising hopes for future therapies. Share: Facebook Twitter Pinterest LinkedIN Email FULL STORY Scientists at Texas Children’s Duncan Neurological Research Institute and Baylor College of Medicine have uncovered a promising new strategy that could one day help treat Rett syndrome, a rare genetic brain disorder that mainly affects girls and currently has no cure. Credit: AI/ScienceDaily.com Researchers at Texas Children's Duncan Neurological Research Institute (NRI) and Baylor College of Medicine have reported a promising experimental strategy that could eventually help treat Rett syndrome. Their findings, published in Science Translational Medicine , describe a potential way to increase levels of a key brain protein that is disrupted in the disorder. The work offers early hope for addressing a rare neurodevelopmental disease that currently has no cure. "Rett syndrome is a rare genetic neurodevelopmental condition that causes a regression in development, typically after 6 to 18 months of normal growth, leading to severe impairments in motor skills, speech and communication," said corresponding author Dr. Huda Zoghbi, director of the Duncan NRI, Distinguished Service Professor at Baylor, and a Howard Hughes Medical Institute investigator. "The disorder primarily affects girls; about 1 in 10,000 live births." How MECP2 Mutations Disrupt Brain Function Rett syndrome results from loss of function mutations in the MECP2 gene. This gene plays a critical role in the brain because it regulates the activity of many other genes involved in neurological processes. When the gene is altered, the resulting MeCP2 protein may be missing entirely or unable to function normally. In some cases, mutant forms of MeCP2 are produced in smaller amounts or have reduced ability to bind DNA, which is essential for carrying out its role in controlling gene activity. Experiments in mouse models have shown that Rett syndrome symptoms can be reversed under certain conditions. When healthy MeCP2 protein is introduced into the brains of these animals, their symptoms improve. Researchers have also found that increasing the amount of a partially functional mutant MeCP2 protein can lead to improvements in survival, movement, and breathing problems in mice. "This is important because about 65% of patients with Rett syndrome have partially functional MeCP2 that either has decreased DNA binding or is less abundant than normal," said first author Harini Tirumala, graduate student of molecular and human genetics in the Zoghbi lab. "Working with mouse models and cells derived from patients with Rett syndrome, our study provides proof of concept that increasing the levels of mutant MeCP2 in patients with the condition could provide therapeutic benefit." Understanding MECP2 Protein Variants Developing treatments that adjust MeCP2 levels is challenging because the brain requires the protein to stay within a narrow range. Too little MeCP2 leads to Rett syndrome, while excessive amounts cause another neurological disorder known as MECP2 Duplication Syndrome. Achieving the right balance has been a major obstacle for therapy development. "We knew from previous studies that the brain normally produces two slightly different versions of the MeCP2 protein, known as E1 and E2," Zoghbi said. "These versions come from the same gene, which is processed one way to produce E1 and a different way for E2." A useful way to picture this process is to think of the gene as a recipe for building the protein. The instructions contain four components: e1, e2, e3 and e4. To make the MeCP2 E1 protein, cells combine e1, e3 and e4. To produce MeCP2 E2, cells include all four components, meaning the e2 segment appears only in the E2 version. The brain produces both proteins, but E1 is the more abundant form. "We also knew that there have been no reports of Rett syndrome patients carrying mutations on E2 protein. Only mutations that disrupt E1 protein cause the condition," Tirumala said. "Studies in mice support this observation." "Altogether, we knew that MeCP2-E2 differs from MeCP2-E1 by a single ingredient in the gene, is less abundant than E1, is not associated with Rett syndrome and is not needed for MeCP2 function in the brain," Tirumala said. "This led us to hypothesize that guiding brain cells to skip the e2 ingredient would promot