‘Bubble baby disease’ will one day be a thing of the past. That’s a bold statement, but I say it with confidence because of the recent advancements in stem cell gene therapies that are curing infants of this life-threatening immune disease.
The scientific name for ‘bubble baby disease’ is severe combined immunodeficiency (SCID). It prevents the proper development of important immune cells called B and T cells, leaving newborns without a functioning immune system. Because of this, SCID babies are highly susceptible to deadly infections, and without treatment, most of these babies do not live past their first year. Even a simple cold virus can be fatal.
Scientists are working hard to develop stem cell-based gene therapies that will cure SCID babies in their first months of life before they succumb to infections. The technology involves taking blood stem cells from a patient’s bone marrow and genetically correcting the SCID mutation in the DNA of these cells. The corrected stem cells are then transplanted back into the patient where they can grow and regenerate a healthy immune system. Early-stage clinical trials testing these stem cell gene therapies are showing very encouraging results. We’ll share a few of these stories with you below.
CIRM-funded trials for SCID
CIRM is funding three clinical trials, one from UCLA, one at Stanford and one from UCSF & St. Jude Children’s Research Hospital, that are treating different forms of SCID using stem cell gene therapies.
Adenosine Deaminase-Deficient SCID
The first trial is targeting a form of the disease called adenosine deaminase-deficient SCID or ADA-SCID. Patients with ADA-SCID are unable to make an enzyme that is essential for the function of infection-fighting immune cells called lymphocytes. Without working lymphocytes, infants eventually are diagnosed with SCID at 6 months. ADA-SCID occurs in approximately 1 in 200,000 newborns and makes up 15% of SCID cases.
CIRM is funding a Phase 2 trial for ADA-SCID that is testing a stem cell gene therapy called OTL-101 developed by Dr. Don Kohn and his team at UCLA and a company called Orchard Therapeutics. 10 patients were treated in the trial, and amazingly, nine of these patients were cured of their disease. The 10th patient was a teenager who received the treatment knowing that it might not work as it does in infants. You can read more about this trial in our blog from earlier this year.
In a recent news release, Orchard Therapeutics announced that the US Food and Drug Administration (FDA) has awarded Rare Pediatric Disease Designation to OTL-101, meaning that the company will qualify for priority review for drug approval by the FDA. You can read more about what this designation means in this blog.
X-linked SCID
The second SCID trial that CIRM funds is treating patients with X‑linked SCID. A mutation on a gene located on the X chromosome causes this disease. Because the gene is X‑linked, the disorder usually affects boys who inherit the mutation from their mothers. X‑linked SCID is the most common form of SCID and occurs in about one in 60,000 infants.
UCSF and St. Jude Children’s Research Hospital are running a Phase 1/2 trial for X‑linked SCID. Dr. Brian Sorrentino leads the study. The team collects a patient’s own blood stem cells, modifies them, and returns them to rebuild a healthy immune system. Patients do receive chemotherapy to remove diseased bone marrow. However, UCSF doctors are optimizing low‑dose chemotherapy to limit long‑term effects. According to a UCSF news release, the trial plans to treat 15 children over five years. Several children have already begun treatment, and more updates are expected next year.
CIRM is also funding a third trial at Stanford University Dr. Judy Shizuru leads a team developing a therapy that removes unhealthy blood stem cells before a transplant. This approach aims to improve the survival and engraftment of healthy donor cells. You can read more about this trial on our clinical trials page.
SCID Patients Cured by Stem Cells
These clinical trial results are exciting. Even more exciting are the patient stories we can share. We spoke with several families whose children joined the UCLA and UCSF–St. Jude trials. We asked them to share their experiences so other families know that hope exists. Their stories reveal both heartbreak and joyful celebration.
Evie is now six years old. She was diagnosed with ADA‑SCID when she was only a few months old. Thanks to Don Kohn and the UCLA trial, she is now cured. Her mom gave a moving presentation about Evie’s journey at the CIRM Bridges Trainee Annual Meeting in July. You can watch the 20‑minute talk below.
Ronnie’s story
Ronnie was diagnosed with X‑linked SCID just days after birth. He was still under a year old when doctors told his parents about the UCSF–St. Jude trial. Thanks to that referral, Ronnie received life‑saving stem cell gene therapy before he turned six months old.
Now he is building a healthy immune system. He is back home and doing well with his family. Ronnie’s dad, Pawash, shared their moving story at our September Board meeting, and you can watch it in the linked video.
At CIRM, our mission is to speed stem cell treatments to patients with urgent medical needs. By funding promising clinical trials like those highlighted here, we hope to help create approved stem cell therapies for SCID and other life‑threatening diseases.