California Pumping $20 Million into Stem Cell/Gene Therapy for 'Bubble Boy' Syndrome

June 2016 video from UCLA

Highlights
30 out of 30 cured
$18.2 million in matching funds
Cells to be frozen
UK's Orchard Therapeutics partnering

California's stem cell agency is ready to award $20 million on Thursday to a UCLA researcher to assist in his 30-year search for a widely available cure for what has come to be known as the "bubble boy" syndrome-- severe combined immunodeficiency (SCID).

The California scientist is Donald Kohn, of the Broad Stem Cell Research Center at UCLA, who said today that 30 out of 30 babies have already been cured using his type of therapy. Kohn said that the research involving the extremely rare disease could lead to progress in treating other afflictions ranging from sickle cell disease to cancer.

The progress in treating the "bubble boy" disease is much changed from decades ago when the case of David Vetter captured the nation's attention as the boy who was "born into a world he could not touch."  He ultimately died at the age of 12. (This item continues below video.)

Kohn's proposal for an early stage clinical trial would be co-funded with $18.2 million and would test a stem cell and gene product known as OTL-101. It could replace what the stem cell agency said were the "suboptimal," current treatments for  Adenosine Deaminase Severe Combined Immunodeficiency.

The affliction is extremely rare and occurs in less than one in 100,000 births worldwide, according to Wikipedia. Without treatment, children can die before the age of two.

The agency's application review summary said that reviewers were "highly enthusiastic" about Kohn's proposal during their closed-door session last month. The summary said that reviewers, who are from out-of-state and do not publicly disclose their economic interests, "applauded the move to a cryopreserved product that will allow improved patient access to the therapy." They also noted that the costs of the trial are "exceedingly high."

In response to a query by the California Stem Cell Report, Kohn said today via email, 

"Building upon the previous success of our single-site trials for ADA SCID, which have resulted in 30 out of 30 babies cured, our next trial will focus on developing a cryopreserved formulation of the cell product. 

"This has several potential advantages. It will allow the cell product to undergo full testing before the transplant is performed, whereas currently we only have stat viability, sterility and endotoxin assay results, with gene transfer efficiency measurements coming later.

"Additionally, it provides more time to split up the dosing of the conditioning chemotherapy and individually adjust the total dose based on measurement of the individual patient's unique drug clearance activity.

"Finally, this will allow centralization of cell processing, allowing patients to remain at their local hospital for the treatment, with the stem cells traveling to a commercial cell processing site, gene-corrected, frozen and shipped back to their hospital for infusion."

The agency's board is virtually certain to ratify the decision of reviewers at its telephonic meeting on Thursday. It has almost never overturned a positive recommendation by reviewers. 

The agency, formally known as the California Institute for Regenerative Medicine (CIRM), did not release Kohn's name in advance of the Thursday meeting. Its policy, with some notable exceptions, is to withhold that information until the pro forma vote by its governing board. The California Stem Cell Report identified Kohn as the recipient through a number of public documents. The UCLA researcher has already received $32 million from CIRM for his work. 

Kohn has teamed with Orchard Therapeutics Ltd. of Britain, a firm that began operations last May with a $33 million war chest. Kohn is one of the scientific advisors to the company. He said today: 

"This study is being done at the UCLA Broad Stem Cell Research Center in partnership with Orchard Therapeutics Ltd., who have licensed this stem cell gene therapeutic from UCLA and University College London, UK. The general approach of stem cell gene therapy was first done for ADA SCID, which is a highly favorable disease for this treatment. Findings and advances made for this disorder are being applied to many other inherited diseases, such as Sickle Cell Disease, other Primary Immune Deficiencies, Storage and Metabolic Diseases, as well as HIV/AIDS, cancer and leukemia."

The process uses a patient’s own stem cells. Earlier this year, the company said that the cells are "modified with a functioning copy of the missing or faulty gene before being transplanted back into the patient’s body. The use of the patient’s own cells (autologous) removes the need to search for a matching stem cell donor, which can take months or even years," the company said.

Should the treatment emerge successfully from the clinical trials, it will face competition from a rival developed by GlaxoSmithKline that has been approved for use in Europe at a reported cost of $665,000 per patient. Glaxo is expected to seek approval next year for use of the treatment in the United States, which has only about 12 new cases a year, according to the STAT health science news service. However, a document from the U.S. Center for Disease Control places incidence at 40 to 100 new cases each year. 

The public can participate in Thursday's meeting at locations in Oakland, San Francisco, San Diego, Napa, South San Francisco, San Francisco, Beverly Hills, Fresno, Elk Grove, Los Gatos, Sacramento, and Irvine.  It is also being audiocast on the internet. Instructions and addresses can be found on the agenda.

(Editor's note: An earlier version of this item incorrectly reported that co-funding on this award totalled $8.9 million. The correct figure is $18.9 million.)