Bubble Babies, Cures and California's Stem Cell Agency

Alysia Padilla-Vacarro and daughter, Evangelina, on the day
 of the baby's life-saving gene therapy treatment at UCLA.
UCLA photo

Numbers speak loudly in America. We focus intently – sometimes obsessively -- on everything from baseball statistics to the latest count of illegal immigrants. Numbers appear to create certainty and tend to drive discussion of public issues.

Which is where the California stem cell agency comes in.  Executives at the agency point with pride to the 10 clinical trials that it has helped to fund. They do not point to the zero number of therapies that the agency has placed in the public marketplace despite the apparent promises of the ballot campaign that created the research effort 10 years ago this month.

Nonetheless, agency has chalked up some indirect scores that are difficult to quantify but deserve ample consideration when evaluating the California Institute for Regenerative Medicine(CIRM), as the agency is formally known.

One dramatic example gained national media attention last week. The case involves work at UCLA for what appears to be a cure for the fatal “bubble boy” syndrome. The term was coined back in the 1970s when stories involving a youngster in Texas made headlines across the country.  The child had to live inside a plastic bubble because his immune system was compromised. The case even inspired a 1976 movie called “The Boy in the Plastic Bubble” starring John Travolta. (See here, here and here.)

Enter Donald Kohn, many years later.  Kohn is director of the Human Gene Medicine program at UCLA. And last week, the Los Angeles university announced that Kohn and his team have developed a treatment that cures the “bubble boy” syndrome by altering the genes of the afflicted children.  In clinical trials, the UCLA announcement said, the lives of 18 children were saved.

Kohn used a virus delivery system that he first developed in his lab in the 1990s. But the work on the gene treatment began in earnest in 2009 and involved two, multi-year clinical trials.

UCLA's Nov. 18 news release described the treatment simply like this:

“During the trials, the patient's blood stem cells were removed from their bone marrow and genetically modified to correct the defect.”

The stem cell agency did not directly fund Kohn’s “bubble” research, but some of its other funding at UCLA contributed to the effort. Specifically, the work was performed in the stem cell research facility that CIRM helped to finance. Kohn’s lab is in the “shared research lab” space funded by CIRM in still another program. The research was also aided by persons working in two other separate CIRM training programs.

The next step for Kohn will be to use the research in proposed clinical trials involving sickle cell anemia, which are being financed by CIRM to the tune of $13.1 million. They will also be part of the agency’s Alpha clinic program.

Steve Peckman, associate director of the UCLA stem cell center, said the Kohn research “is a perfect example of how CIRM support at all levels is critical to achieve the goal of driving scientific discoveries to the clinic.”

Kohn’s work was cited last week at a Los Angeles media event celebrating CIRM’s 10th birthday. Maria Shriver, the former first lady of California and whose father died of Alzheimer’s Disease, wrote about the research and linked it glowingly to the stem cell agency in an item on the Huffington Post on Nov. 20.  She said,

“The news about 'bubble baby' disease is just the start. I am convinced that stem cell research means we Baby Boomers will be the last generation to have to watch our parents die of Alzheimer's or watch our children die prematurely of sickle cell disease. Proposition 71 (which created the stem cell agency) set this research in motion. Now we have to make sure this research keeps moving forward.” 

While CIRM deserves credit for its role in Kohn’s work, it is only one of 10 entities cited by UCLA as contributing but without providing figures.  Accurately quantifying CIRM’s contribution is difficult if not impossible. That said, it was significant. The agency’s programs do ripple out – not only at UCLA but globally.  They add to the bank of knowledge about stem cells, all of which creates an easier path to the ultimate development of new therapies.

 

Ironically, one of the CIRM programs -- the "shared labs" -- that helped Kohn has expired despite pleas by some of the state’s top stem cell scientists. News about that program surfaced again a few days after the Kohn announcement. Without mentioning Kohn, Jeanne Loring, head of the stem cell program at Scripps, discussed the importance of the "shared labs" in a piece on the blog of UC Davis stem cell researcher Paul Knoepfler.

Loring said the program has had “an enormous impact beyond (its) original intention.” 

In her “open letter to CIRM,” she said,

“Unwittingly, CIRM’s shared lab program jump-started human stem cell research in California, sending it on a trajectory that has led to stem cell clinical trials in just 6 years….CIRM did not expect that there would be interaction among the labs that would make the whole greater than the sum of the parts. The network of shared labs became our means to communicate and share ideas. It sparked new partnerships between institutions throughout the state, and became a conduit for trainees to move from CIRM’s Bridges internships to graduate school. One scientist described the shared labs as ‘the beating heart of California’s stem cell program.’”

She noted that the program was discussed by the CIRM governing board in December 2013 at a time when the directors were being told that the money for new grants would run out in 2017. Today, however, Randy Mills, the new CIRM president, has reexamined the financial assumptions and says the money will be around until 2020.

Loring and 11 other researchers are asking the CIRM governing board at its December board meeting to provide the go-ahead for applications for another round of funding for what they say is the key maintaining the rapid pace of stem cell research in California.

Anything less, they say, would impede the development of stem cell treatments and waste a good portion of the $20 million already spent on the “shared labs” effort.

Perhaps Donald Kohn would agree as well. 

Here is a two-minute CIRM video of Kohn explaining his work.