Grant provides hope for children with DiGeorge syndrome

August 10, 2018

Charlie Steven is a bubbly 7-month old from Southern California who has is like any other infant except that he has been born without a functioning thymus. As a result, he is highly susceptible to infections and has lived in a neonatal intensive care unit since birth. A large research grant from the California Institute for Regenerative Medicine (CIRM) to two Stanford researchers has given new hope to children like Charlie, who have a rare disorder called complete DiGeorge syndrome, which is caused by a genetic deletion that keeps the thymus from forming properly during development.

The researchers, Vittorio Sebastiano, PhD and Katja Weinacht, MD, PhD plan toapply stem cell technology to treat children who have no functioning thymus. Because the thymus is essential for developing immune cells called T-cells, children with DiGeorge syndrome are left without a functional immune system. They are condemned to live in medical facilities to lower the risk of infection and treat infections immediately if they occur. The life expectancy of children with this condition is only about a year. The only treatment that can cure the disorder is a thymic transplant. Because the only thymic transplant program in the United States was put on hold last year, there is currently no treatment for DiGeorge syndrome children in the country.

Sebastiano, an assistant professor of obstetrics and gynecology from the Stanford Institute for Stem Cell Biology and Regenerative Medicine, and Weinacht, an assistant professor of pediatrics from the Division of Stem Cell Transplantation and Regenerative Medicine, were awarded a discovery grant of about $850,000 from CIRM to develop a new platform making new thymic tissues to cure these kids. Ultimately, Sebastiano and Weinacht want to take a few cells and change those cells into embryonic-like cells called induced-pluripotent stem (iPS) cells. They will then guide those cells’ development into functional thymic tissue.

This approach to thymic regeneration, if successful, has therapeutic potential for a broad range of clinical applications, including promoting immune function in blood stem cell transplant recipients, reducing rejection of organ transplants, and treating autoimmune disorder. “Thymic engineering may even hold the promise  for boosting immune activity in general, in particular in the aging population”, says Sebastiano.

The researchers’ immediate goal, however, is helping DiGeorge syndrome children. “We are focused on helping Charlie and all the other children born without a thymus, so that they can receive life-saving therapy and return home to their families,” Weinacht says.