Dr. Huda Zoghbi, Director of Texas Children’s Jan and Dan Duncan Neurological Research Institute (Duncan NRI), is determined to give children with Rett syndrome a future full of possibilities.
“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,” Dr. Zoghbi said. “The disorder primarily affects girls; about 1 in 10,000 live births.”
Dr. Zoghbi and her team at Baylor College of Medicine and Duncan NRI are exploring a way to increase the amount of a partially working brain protein called MeCP2, which is essential for brain cells to communicate. The protein comes in two forms, E1 and E2. Mutations in E1 cause Rett syndrome, while E2 is harmless.
By guiding cells to skip E2, the team increased E1 levels by 50% to 60% in mice. Patient-derived cells responded in the lab, regaining normal shape, electrical activity and the ability to regulate other genes. This shows that partially functional proteins can be strengthened to help brain cells work more normally.
The work provides early proof of concept for a potential therapy for the neurodevelopmental disorder, which currently has no cure.
“Our work lays the foundation and provides preclinical evidence for a therapeutic approach for Rett syndrome that increases MeCP2 and confers functional improvement,” Dr. Zoghbi said. “Although morpholinos themselves are not an option because of their toxicity, similar strategies, like antisense oligonucleotide therapies already used in other conditions, could potentially be developed for Rett syndrome.”
Dr. Zoghbi’s work on Rett syndrome has also earned her the inaugural Nancy Lurie Marks Prize for Autism Research, the highest honor awarded by the Lurie Autism Institute, recognizing scientists whose work has made transformative contributions to autism research.
Dr. Zoghbi was recognized for her groundbreaking work uncovering the genetic causes of neurological disorders, including her landmark discovery that mutations in the MECP2 gene cause Rett syndrome, an autism-related neurodevelopmental disorder. This discovery fundamentally changed how scientists understand autism genetics and has helped guide decades of research aimed at identifying potential treatment pathways.
“Dr. Zoghbi’s record speaks for itself, and we couldn’t think of a more deserving inaugural recipient who exemplifies the pioneering work in autism research that the Lurie Autism Institute wants to make possible,” said prize committee chair Frances E. Jensen, MD, Chair of the Department of Neurology and Professor of Neurology at the Perelman School of Medicine at the University of Pennsylvania and co-director of the Penn Translational Neuroscience Center.
