CIRM funds many projects seeking to better understand Severe Combined Immune Deficiency (SCID) and other primary immunodeficiency diseases to translate those discoveries into new therapies.
Primary immunodeficiencies are disease that compromise or destroy the immune system, leaving patients susceptible to serious infections. Typically, these diseases have genetic causes and many of them are rare. Severe combined immune deficiency or SCID is an example of a primary immunodeficiency.
SCID – also known as ‘bubble boy disease’ - is a rare genetic disorder, effecting one in 30,000 newborns. Left untreated the children die before the age of 2, and the only readily available treatment involves high-risk bone marrow transplants. Because these patients already have a compromised immune system, 10 to 20 percent don’t survive the transplant.
Gene therapy has been used to correct the defect in certain types of SCID, but early gene modifying techniques resulted in some patients developing cancer. Newer gene therapy techniques appear to be safer but have been tried on fewer than 20 patients.
Researchers funded by California’s stem cell agency are looking for a better alternative to help these children. They are trying to improve the safety of bone marrow transplant (BMT), which essentially uses the stem cells in bone marrow to give the children a new immune system that works properly. Most of the risk of current BMT procedures comes from the radiation or chemotherapy given to patients before the transplant to wipe out the patient’s own stem cells that form immune cells. These regimens kill many types of cells beyond those intended and result in numerous toxic side effects.
Clinical Stage Programs
Stanford School of Medicine (X-linked SCID)
This team proposes to replace SCID patients’ dysfunctional immune cells with healthy ones using a safer form of bone marrow transplant (BMT). They plan to eliminate the bad cells with an antibody, a protein, that very specifically targets and eliminates blood forming stem cells. If successful, the procedure could open up similar BMT therapies to patients with other auto-immune diseases such as multiple sclerosis, lupus or diabetes that are generally not candidates for BMT currently. These diseases, while debilitating, are not immediately life-threatening and generally don’t warrant the risks involved in BMT the way it is done today.
The team is using gene therapy to correct a genetic mutation in the blood stem cells of patients with X-linked SCID. The corrected stem cells are then transplanted back into the patient to restore their immune system's ability to produce healthy immune cells. This will allow the patient to fight off infections and will hopefully cure their disease.
University of California, Los Angeles (Chronic granulomatous disease and ADA-SCID)
The team is developing a therapy for chronic granulomatous disease: a very rare primary immune deficiency disease that results in severe and recurrent infections that can impact quality and length of life. The UCLA team uses the patient’s own genetically modified blood stem cells to create a new blood supply and immune system to eradicate the problem.
UCLA is also developing a therapy for a form of SCID called adenosine deaminase (ADA)-deficient SCID. Patients with ADA-SCID lack an important enzyme called adenosine deaminase in their immune cells. Without this enzyme, toxic by-products build up in their immune cells and eventually kill them off leaving the patient susceptible to deadly infections. The group from UCLA will genetically modify patient blood stem cells to remove the disease-causing mutation and transplant these corrected stem cells back into the patient to create a new, healthy immune system.