Immunodysregulation polyendocrinopathy enteropathy X-linked (IPEX) Syndrome

What is IPEX syndrome?

IPEX is a genetic disease of immune dysregulation in which patients can present early in life with diarrheadiabetes and eczema. It is extremely rare, affecting 1 in every 1.6 million people.

Patients with IPEX have abnormalities in the FOXP3 gene, which controls the production of regulatory T cells, a type of immune cell. Without a normal FOXP3 gene, other immune cells attack the body’s healthy tissues. The gene is carried on the X chromosome, so most patients are male. Patients are routinely treated with immunosuppressive drugs, especially rapamycin, with variable success. 

How do we treat IPEX at Stanford Children’s Health?

The only curative therapy for IPEX is an allogeneic stem cell transplant from a donor with a healthy immune system. Both matched siblings and mismatched donors have been successfully used. The major determinant of the success of the stem cell transplant is the clinical condition of the patient at the time of transplantation, with stable patients doing better.

Patients receive chemotherapy before transplantation to enable stem cell engraftment and reduce their autoinflammatory symptoms. Patients are usually discharged from the hospital 50 – 60 days after their transplant when they have developed normal immune and blood function and their preexisting autoinflammatory symptoms have cleared.

Why choose Stanford Children’s Health for IPEX treatment?

Stanford’s Rosa Bacchetta, MD, is a world-renowned expert in IPEX. She has been performing stem cell transplants in patients with IPEX since 2003, shortly after the FOXP3 gene was identified. Her laboratory is working on two different gene therapy approaches to treat IPEX. In one method, doctors will take a patient’s white blood cells and add a normal copy of the FOXP3 gene to the cells, transforming them into regulatory T cells to help restore normal immune function. Dr. Bacchetta is preparing to move this approach to human clinical trials.

Her team is also testing whether they can use CRISPR-Cas9 gene-editing technology to insert a functional FOXP3 gene into IPEX patients’ stem cells. Patients would receive a transplant with their own corrected stem cells. If this method works, it will be a permanent cure.