Rare stem cell success gives young girl life outside the bubble

One year ago this month, five-year-old Sheersha Sulack asked Santa to bring her a suitcase to carry her toys with her for an arduous treatment that her parents hoped would save her from a rare, life-threatening affliction known as the bubble baby disease.

Today, she is at home in Tehachapi with her parents, an 11-year-old sister, Skylar, and a nine-year-old brother, Stephen, eagerly anticipating a different sort of Christmas. Now six years old, Sheersha has received the gene and stem cell treatment and is doing well.

“I don’t need big shots anymore,” Sheersha tells her mother, Shayla.

Sheersha’s experience is a small chapter in a long story. The saga involves tens of millions of California taxpayer dollars, a nearly miraculous therapy, decades of scientific work, a recalcitrant company, despair, hope and much more. And it is still not over.

Development of the therapy is part of a unique effort that has put the Golden State at the forefront of the development of gene and cell therapies. No other state in the nation has invested the billions that state taxpayers are providing. Gene therapies are hailed as revolutionary and expected to cure previously uncurable afflictions. Earlier this month, approval by the Food and Drug Administration of two gene therapies for sickle cell diseases captured celebratory, national headlines.

The treatments, however, carry astronomical price tags – $2 million to $3 million. The cost and the small number of patients pose unprecedented challenges for companies and patients.

In the case of the bubble baby disease, only 76 children are estimated to be born each year with the genetic affliction in the United States. Medically known as ADA-SCID, it means that a baby is born without an immune system. Without appropriate treatment, the children will die.

It is the same rare disease portrayed in the 1976 John Travolta movie, “The Boy in the Plastic Bubble.”

Sheersha and her parents had to wait six years for her treatment in a clinical trial at UCLA directed by scientist Donald Kohn and his team. His work surrounding the bubble baby disease has been supported with $43 million from the California stem cell agency, officially known as the California Institute for Regenerative Medicine (CIRM).

Development of the therapy is part of a unique effort that has put the Golden State at the forefront of the development of gene and cell therapies.

The clinical trial hit a wall three years ago when the company that licensed the therapy from UCLA, Orchard Therapeutics, PLC, abandoned it. The company preferred to focus on research that it deemed would be more profitable. In May of 2021, Capitol Weekly was the first to report that Orchard had rejected a “desperate call for help” to treat more than 20 children whose parents had asked the company to treat their children.

Fourteen days after the initial Capitol Weekly story, Orchard returned the license to CIRM. But it wasn’t until this year that the trial resumed. Three children, including Sheersha, have since been treated. A fourth has just started the process. Kohn, who began his work 40 years ago, hopes to treat another three to six patients next year. Kohn and his collaborators reported in the New England Journal of Medicine in May of 2021 that the overall survival rate was 100 percent in a trial that had 50 patients. 

In a recent interview, Kohn said his team is making progress in commercializing the therapy so that it can be used outside of a clinical trial. He is also involved in another trial to create a new gene therapy for sickle cell disease in partnership with the University of California (UC), San Francisco, and UC Berkeley. CIRM has backed that effort with $28 million.

Making the bubble baby therapy more widely available is no small matter and involves more than the science. National Resilience, Inc., a private firm located in San Diego, is helping with a plan for commercialization, Kohn said. National Resilience is a “contract development and manufacturing organization” (CDMO in biomedical jargon). The firm says on its website:

“The technology of manufacturing complex medicines, like cell and gene therapies, hasn’t kept pace with the wave of scientific discoveries fueling them.

“Decades of misalignment and under-investment have left the biomanufacturing industry unable to capitalize on its own discoveries – and vulnerable to dynamics that disrupt the delivery of life-saving therapies.”

Kohn has a meeting scheduled with the FDA in January to discuss what is needed to move forward. The creation of a spin-out company that would license the therapy from UCLA is also on Kohn’s agenda. The new company would contract with a CDMO for manufacturing and commercialization on a sustainable basis. It is likely to take more than two years to work out all the details and win federal approval.

“Accessible availability, sustainability are the keys. It’s a curative therapy. It has to fit into some business model to keep it going,” Kohn said.

Kohn expects to apply next year to CIRM for more millions to extend the bubble baby trial and tackle commercialization. He may use two new initiatives approved this month by the CIRM board. One would ease CIRM’s hefty co-funding requirements for later-stage clinical trials. Another creates a new program specifically to support essential pre-commercial activities at $12 million per award.

So far, however, CIRM has yet to back a stem cell or gene therapy that is available to the general public. And its funds are expected to run out in nine years or less.

CIRM, which has about $4 billion available for research awards, pledged in 2021 to support Kohn’s work. It said in a recent statement, “CIRM celebrates the recent success of the Kohn ADA-SCID trial. CIRM remains dedicated to supporting innovative research that holds the promise of life-changing treatments for individuals facing serious and life-threatening conditions. We are committed to bringing transformative therapies to patients.”

Despite the billions that CIRM can spend on gene and stem cell research, CIRM’s bubble baby saga and its role in financing revolutionary therapies rarely receive attention in the mainstream media. One exception was a lengthy CNN feature last April about Sheersha that began:

“Later this spring, a little girl in California who essentially has no immune system will receive a lifesaving treatment for ‘bubble boy disease’ thanks to the persistence of a dogged group of parents, a pediatrician, a veteran newsman and a few episodes of ‘Grey’s Anatomy.’”

CIRM was created 19 years ago when voters approved a $3 billion ballot initiative largely aimed at human embryonic stem cell research. In 2020, voters refinanced it with $5.5 billion and loaded it with additional responsibilities. One was a specific go-ahead on gene therapies. Another charged CIRM with devising ways to make the multimillion-dollar therapies affordable.

So far, however, CIRM has yet to back a stem cell or gene therapy that is available to the general public. And its funds are expected to run out in nine years or less. Then CIRM will need to seek more billions from California voters, who narrowly approved its refinancing in 2020 on a 51 percent to 49 percent vote.

In Tehachapi, a small, mountain town southeast of Bakersfield, Shayla Sulack, Sheersha’s mom, is not too concerned about CIRM’s billions. But she is concerned about the more than 20 children on a waiting list to receive Kohn’s treatment.

“We should have more access” to these sorts of therapies that are “done and ready,” Shayla said in an interview.

As for her daughter and the therapy, “It looks to be successful, and we hope that it is successful. She’s off all the medicines. She gets to live a relatively normal life.”

No more big shots, as Sheersha says.

Jensen is a retired newsman and has covered CIRM for 19 years on his newsletter, the California Stem Cell Report. He authored the book, “California’s Great Stem Cell Experiment,” in 2020.