Engineering Enteric Gila for Neuroregeneration in Hirschsprung Disease
Hirschsprung disease is a serious condition that affects the large intestine (colon) in infants and children. It occurs when nerve cells that control the muscles in the gut do not fully develop before birth. This causes parts of the intestine to lack the ability to move waste normally, leading to severe constipation, abdominal swelling, and sometimes life-threatening infections. Right now, the only treatment is surgery to remove the section of the intestine that lacks these nerve cells. However, even after surgery, many children continue to struggle with bowel problems, including incontinence, constipation, and infections. This shows that current treatments do not fully restore normal function.
Dr. Rhian Stavely’s research aims to develop new ways to repair the nervous system of the gut. His work focuses on a type of cell in the intestine called enteric glial cells. These cells normally support nerve function, but recent research from his lab has shown that some of them may have the ability to turn into nerve cells themselves. In studies using a mouse model of Hirschsprung disease, his team discovered that a special group of these glial cells, that possess the ability to become nerve cells, are missing in the parts of the colon without nerves.
This project has three goals: First, to study and understand the missing group of glial cells. Second, to test whether putting these cells back into the intestine can help rebuild the missing nerve networks. Third, to use gene therapy to “reprogram” the remaining glial cells in the gut so they can become nerve cells and restore normal bowel function.
This research has the potential to change how Hirschsprung disease is treated, by moving beyond surgery and toward therapies that restore healthy nerve function. It may also lead to new treatments for other gut-related nerve disorders in children. The long-term goal is to give children with Hirschsprung disease better outcomes and healthier lives.