DNA changes that contribute to Spina Bifida during embryogenesis open the door to potential treatments

Scientists from the Rady Children’s Institute for Genomic Medicine and the Department of Neuroscience and Pediatrics at the University of California, have made an important breakthrough in understanding the causes of Spina Bifida, a serious congenital anomaly affecting thousands of newborns each year.

The new study, published in Naturereveals critical information on how this condition develops and opens the door to potential future treatments.

The Spina Bifida, or Meningomyelocele, occurs when the spine and the spinal cord do not form properly at the beginning of pregnancy. Most often identified during prenatal ultrasound, the condition can lead to lifetime disabilities of the lower limbs and the bladder. The sequencing of the newborn is not systematically used in this condition because the causes remain unknown. While researchers have long understood certain environmental risk factors, the new study offers a more in-depth overview of the underlying molecular mechanisms.

“Our research identifies specific stages of embryogenesis that contribute to Spina Bifida,” said Dr. Joseph Gleeson, principal of the study and professor at Rady Children’s and UC San Diego. “This is a major step to understand why this condition occurs and how we could one day prevent it.”

New perspectives on the origins of Spina Bifida

The study has made a daring affirmation, since new DNA changes, not present as a mother or father, contribute to the cause. The test of this assertion required that people with Spina Bifida and their parents volunteer for the study. To achieve enough families for the study, the authors have established the Spina Bifida sequencing consortium. This allowed the aggregation of older and younger people from around the world.

“The combination of DNA mutations has revealed functional modules that contribute to the risk of illness,” said Dr. Sangwoo Kim, Co-Sensior author and professor at Yonsei University College of Medicine, Republic of Korea. Researchers have found that almost a quarter of patients have such mutations that contribute to the risk of illness and that these mutations have an impact on how the embryo cells connect to each other. These results question the previous hypotheses and show that many patients have a single gene which is the likely cause.

One of the most exciting aspects of the study is its potential impact on early diagnosis and intervention.

“Our results identifying genetic risk factors can now be used to develop new screening tools to obtain a more precise and earlier diagnosis, and possibly predict the degree of handicap,” said the first author, Dr. Yoo-Jin Ha, affiliated both UC San Diego and Yonsei.

Hope for future treatments

Beyond improving the diagnosis, this research opens the way to potential treatments. The study suggests that new approaches to study the causes using stem cell models could be used to advance new interventions such as gene therapy, targeted drugs or nutritional interventions. Although folic acid is established as a significant risk factor, the results offer a promising avenue to further reduce gravity or even prevent Spina Bifida in the future.

“This discovery brings us closer to a day to be able to intervene before the development of the condition,” said Dr. Gleeson. “Currently, fetal surgery to correct the condition after the beginnings has proven promising to reduce the severity of diseases. Although more research is necessary, our results provide a new basis to explore a possible prevention.”

Ahead

The research team plans to rely on these results by incorporating even more powerful DNA transfer methods, in collaboration with the Spina Bifida Sequencing Consortium and the Spina Bifida Association. They hope that continuous research will lead to medical progress that could considerably reduce the impact of Spina Bifida on families around the world.

This study involved collaboration between experts and scientific doctors in more than 30 institutions.

Supplied by Rady Children’s Institute for Genomic Medicine