Dr. Huda Zoghbi awarded prestigious Lundbeck Brain Prize

Dr. Huda Zoghbi, professor and Howard Hughes Medical Institute Investigator at Baylor College of Medicine and director of the Jan and Dan Duncan Neurological Research Institute at Texas Children’s Hospital, has been awarded what is considered one of the world’s most prestigious prizes in brain research, the Lundbeck Foundation Brain Prize.  

Zoghbi is being awarded along with Sir Adrian Bird from the University of Edinburgh, United Kingdom. Both are being honored for their work in Rett syndrome that has led to a better understanding of the disorder and brought researchers closer to a treatment.  

The Brain Prize, which includes research funding, is given once a year in recognition of a researcher’s unprecedented contribution to international brain research. The recipient is nominated by their peers and decided on by a panel of the world’s top neurological researchers. 

“I am deeply honored and humbled to receive this prize and to share this honor with Adrian Bird. This recognition means a lot to me on many levels. It shows support to the families living with Rett syndrome and to my trainees who work tirelessly on this research,” Zoghbi said. “This will allow us to take risks and push the research forward to find a treatment.” 

“Dr. Huda Zoghbi stands out as a leader in this field of research. Because of her dedication to her work and to the families of those who are living with Rett syndrome, we have a better understanding of this disorder as well as a number of other neurological diseases,” said Dr. Paul Klotman, president, CEO and executive dean of Baylor College of Medicine. “As the director of the NRI at Texas Children’s, she has led the way for new discoveries across the field of brain research and we look forward to her continued excellence.”

Zogbhi’s groundbreaking contributions to this research includes identifying the genetic mutation that causes Rett Syndrome, a developmental disease that strikes children, mostly girls, around 1 year old. They begin to regress, showing social withdrawal, loss of hand use and compulsive wringing of the hands, seizures and a variety of neurobehavioral symptoms. Children never recover and will remain developmentally disabled for the rest of their life. 

After seeing patients with these symptoms and identifying other children who had similar symptoms, Zoghbi began research to uncover what caused this disorder. In 1999, she was able to identify that mutations in MECP2 are the cause for Rett syndrome and also revealed that the MeCP2 protein plays a role in various neuronal subtypes.   

Her work showed just how sensitive the brain is to the levels of MeCP2 and that doubling MeCP2 levels causes progressive neurological deficits. This disorder is now recognized as MECP2 duplication syndrome in humans. 

The discovery of the Rett syndrome gene provided a straightforward diagnostic genetic test, allowing early and accurate diagnosis of the syndrome. It also revealed that mutations in MECP2 can cause a host of other neuropsychiatric features ranging from autism to juvenile onset schizophrenia. Further, it provided evidence that an autism spectrum disorder or an intellectual disability disorder can be genetic even if it is not inherited. 

Her discovery opened up a new area of research on the role of epigenetics in neuropsychiatric phenotypes. Epigenetics is the study of changes in organisms caused by modification of gene expression rather than the genetic code. Zoghbi’s use of an antisense oligonucleotide to lower MECP2 levels provides a potential therapeutic strategy for the MECP2 duplication syndrome and inspires similar studies for other duplication disorders. 

While Zoghbi discovered the mutation that leads to Rett syndrome, the MeCP2 protein itself was discovered in 1992 by Sir Adrian Bird as a protein that binds methylated cytosines, an important epigenetic mark in DNA. Dr. Bird generated a mouse model of Rett syndrome and his team went on to show that genetically restoring MeCP2 functional in adult symptomatic mice reversed Rett syndrome features, providing hope of recovery when an effective treatment is developed.  

Learn more about the Lundbeck Foundation Brain Prize.