We now have a better understanding of the earliest manifestations of Rett syndrome, a devastating developmental disorder, thanks to our Sameer Bajikar, PhD, and colleagues.
While doing his postdoctoral work at UVA and Baylor College of Medicine, Bajikar began investigating how mutations in the MECP2 gene cause the development of Rett, a life-shortening condition that affects girls almost exclusively..
He and his collaborators found there was a “cascade” of molecular changes that radically alter how genes work in brain cells. This causes sweeping, “circuit-level” problems in the hippocampus, an area of the brain essential for learning and memory. This, in turn, causes neurons to malfunction.
Professor Bajikar's work sets the stage for developing new ways to treat Rett. For example, the research identified biomarkers that doctors could use to monitor whether the MECP2 gene is working properly as a result of gene therapy. That's important because stimulating the gene too much could cause brain toxicity.
“We discovered several candidate biomarkers sensitive to MECP2 levels that could be the key to developing safe gene therapies for Rett,” Professor Bajikar told me. “Our study more broadly demonstrates the importance of cataloging and understanding the earliest biological events that occur during symptom onset in neurodevelopmental disorders.”