IPEX syndrome is a rare condition where the body can’t control or restrain an immune response, so the person’s immune cells attack their own healthy tissue. The syndrome mostly affects boys, is diagnosed in the first year of life, and is often fatal. Today, the governing Board of the California Institute for Regenerative Medicine (CIRM) invested almost $12 million in a therapy being tested in a clinical trial to help these patients.
Children born with IPEX syndrome have abnormalities in the FOXP3 gene. This gene controls the production of a type of immune cell called a T regulatory, or Treg, cell. Without normal FOXP3+ Treg cells, other immune cells attack the body, leading to the development of IPEX syndrome, Type 1 diabetes, severe eczema, damage to the small intestines and kidneys, and failure to thrive.
Current treatments involve the use of steroids to suppress the immune system – which helps ease symptoms but doesn’t slow down the progression of the disease – or a bone marrow stem cell transplant. However, a transplant requires a healthy, closely matched donor to reduce the risk of a potentially fatal transplant complication called graft-versus-host disease, in which the donated immune cells attack the recipient’s tissues.
Dr. Rosa Bacchetta and her team at Stanford University have developed a therapy that uses the patient’s own natural CD4 T cells, which they genetically modify in the lab to express the FoxP3 gene and convert into Treg cells. Researchers then re-infuse those cells into the patient to determine whether this approach is safe and beneficial. Because the cells come from the patients, there will be fewer concerns about the need for immunosuppressive treatment to stop the body from rejecting the cells. It will also help avoid the challenges of finding a healthy donor and the risk of graft-versus-host disease.
Dr. Bacchetta has received approval from the Food and Drug Administration (FDA) to test this approach in a Phase 1 clinical trial for patients suffering from IPEX syndrome.
“Children with IPEX syndrome clearly represent a group of patients with an unmet medical need, and this therapy could make a huge difference in their lives,” says Dr. Maria T. Millan, the President and CEO of CIRM. “Success of this treatment in this rare disease presents far-reaching potential to develop treatments for a larger number of patients with a broad array of immune disorders resulting from dysfunctional regulatory T cells.”
In addition to a strong scientific recommendation to fund the project, the review team also praised it for the applicants’ commitment to the principles of Diversity, Equity, and Inclusion in their proposal. The project proposes a wide catchment area, with a strong focus on enrolling people who are low-income, uninsured, or members of traditionally overlooked racial and ethnic minority communities.