Prop. 14: USA Today Looks at UCLA Gene Therapy and California's Stem Cell Program

The Lagenhop family in Los Angeles for a clinical
trial to treat their children for a fatal affliction
Harrison Hill/USA Today photo

USA Today has published a lengthy piece involving initial, favorable results from a more than $12 million clinical trial backed by the California stem cell agency and involving a rare disease that usually ends the lives of children before they reach kindergarten age.

The article comes on the eve of the final day for voting on a ballot initiative, Proposition 14, to save the agency from financial extinction by giving it $5.5 billion more. Officially known as the California Institute for Regenerative Medicince (CIRM), the 16-year-old agency is running out of its original $3 billion and is scheduled to begin closing its doors this winter without a boost from the initiative.

The research involves three children from Ohio who are being treated at UCLA in a trial being conducted by Donald Kohn, who has performed other genetic therapy procedures for rare diseases. For the work, CIRM awarded Rocket Pharmaceuticals, Inc., a publicly traded, New York-based firm, $6.6 million in May 2019. The firm provided co-funding of $5.6 million. (Here is a link to the summary of the review of the application, CLIN2-11480.)

Over the years, CIRM has supported Kohn's work with $52 million, not including the Rocket funding. 

The USA Today article by Karen Weintraub began with the case of the family of Alicia and Jon Langenhop of Canton, Ohio. The piece delved into the history of the California stem cell program, but did not mention the agency or its official name.  Proposition 14 was mentioned twice, once in the headline. 

USA Today is a national newspaper. Circulation figures for California are not available, although it reports national, weekly circulation of 726,906. Today's story, which would resonate with many voters, was tucked away in its health section.  

The affliction involved is Leukocyte Adhesion Deficiency-I (LAD-I. 

"Patients with severe LAD-I can develop life-threatening infections because their white blood cells are unable to leave the bloodstream to fight them. Without a successful bone marrow transplant, severe LAD-I is most frequently fatal during the first 2 years of life," the Rocket web site said.

The company's stock price today closed at $28.74, up 70 cents. Its 52-week high is $30.43, and its 52-week low is $9.01. 

USA Today quoted some researchers as saying taxpayer spending has put the Golden State in "the forefront of global stem cell research." The article said, 

"George Daley, a stem cell biologist who is dean of Harvard Medical School, said he's envious of the California researchers who have access to this pot of money.

"'California has always been a very exciting place to pursue science, but prior to (the taxpayer funding), it wasn't exactly the place that was the first on the tip of your tongue as a powerhouse community for stem cell science,' he said. 'But there's no way that today it wouldn't be listed in the top three.'"

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Read all about California's stem cell agency, including Proposition 14,  in David Jensen's new book. Download it from Amazon:  California's Great Stem Cell Experiment: Inside a $3 Billion Search for Stem Cell Cures. Click here for more information on the author.

California Stem Cell Agency: $20 Million Cancer Award from 2012 Bears Clinical Trial Fruit

California's stem cell agency this week took the relatively unusual step of a firing off a double-barreled salute to the beginning of one of its clinical trials -- a $20 million effort based out of UCLA.

Antoni Ribas, UCLA photo

The press release and blog item heralded research by Antoni Ribas, who received the award in 2012 from the California Institute for Regenerative Medicine (CIRM), as the agency is formally known.

The potential treatment deals with the spread of cancer to other
parts of the body, which the agency said is responsible for 90 percent of cancer deaths. Ribas' trial will test a stem cell-based treatment that is better at tracking down and destroying hard-to-treat cancer stem cells. In a news release from UCLA, which is also funding the research, Ribas said,

"(F)ew options exist for the treatment of patients whose cancers have metastasized due to resistance to current therapies. This clinical trial will allow us to try a new approach that engineers the body’s immune system to fight metastasized tumors similar to how it fights germs and viruses.”

Siwen Hu-Lieskovan,
co-investigator, UCLA photo

Maria Millan, interim president of the stem cell agency, said,

“Backed by rigorous science, the stem cell derived T cell immunotherapy being developed by Dr. Ribas and his team has the potential to address advanced cancers that have spread beyond the primary tumor and which are associated with very low survival.

"This trial is the first step in developing a therapy that could alleviate the complications resulting from cancer metastases as well as potentially improving outcomes in cancer patients where there are currently no effective treatment options. We are confident that CIRM’s funding and partnership, in combination with the expertise provided by our Alpha Stem Cell Clinic network, will give provide critical support for the successful conduct of this important clinical trial.”

The $3 billion stem cell agency is actively supporting 33 clinical trials (five involving cancer), which are the last stage prior to approval of a therapy for widespread use. Why the CIRM salute in this case?  The blog item by Todd Dubnicoff said,

"The reality is this: the launch of a clinical trial isn’t a beginning. It represents many years of effort by many researchers and a lot of funding to take an idea and develop it into a tangible product that has been given clearance to be tested in people to potentially save their lives. That’s why this important milestone deserves to be recognized.

More information on the award (DR2A-05309) can be found here. Persons interested in participating in the trial can contact Clinical Research Coordinator Justin Tran by email at justintran@mednet.ucla.edu or by phone at 310-206-2090.

$185 Million California Rumpus over Researcher Raiding

To some outside the California scientific and academic community, it might seem like a cat fight replete with allegations of  a "law-of-the-jungle mindset," loyalty oaths, "petty academic politics" and -- literally -- paper clip theft.

All of which is mentioned in court filings in the squabble, if you want to call it that. But this is not minor stuff. It involves a $185 million, 2015 lawsuit by the University of California (UC) against the University of Southern California (USC), a private school in Los Angeles. Basically, UC wants the money from USC because UC thinks one of its high-powered scientists was hijacked by USC.

Some of the details emerged today in the Los Angeles Times, which wrote about the case in connection with the Carmen Puliafito affair. He is the former dean of the USC school of medicine as well as being a member of the governing board of the $3 billion California stem cell agency, a position he no longer holds.

The headline on the story said,

"USC dean drug scandal could take costly toll on school's legal battle with UC system"

Puliafito was dean of the medical school when it hired away from UC San Diego a star Alzheimer's disease researcher, Paul Aisen, who had the potential of bringing $340 million in research grants to USC. In addition to the prestige of having Aisen on campus, the school would receive a significant percentage of the grants as part of overhead costs.

The Times reported that during Puliafito's eight years at USC, he spearheaded an effort that lured more than 70 "transformative faculty" from UC schools, Stanford, Harvard and other prestigious rivals.

One was USC's longtime athletic rival, UCLA. According to the Times, the successful wooing of Arthur Toga and Paul Thompson, two well-funded neurology researchers, in 2013 "outraged" UCLA, which complained to federal regulators.

The Times wrote,

"It was not unusual for professors to move to other institutions, often with the first university cooperating in the transfer of grant funding to the new school. But in UC’s view, USC had acted beyond accepted norms by targeting academics based on grant funding and strategizing secretly with those researchers while they were still employed by UC about moving grants to USC. The schools reached a confidential settlement requiring USC to pay UCLA more than $2 million, according to a copy of the agreement obtained through a public records request."

The lawsuit is now in San Diego Superior Court. No trial date has been set.

UCLA Snags $3.6 Million from California Stem Cell Agency

UCLA scored today with at least two grants, totaling $3.6 million, from the California stem cell agency. 

Seeking the cash were Donald Kohn,  application 6823, and Gerald Lipshutz, application 6831. Both of the  grants are for $1.8 million each. 

Their applications were initially in the agency's tier two category, which means that CIRM's reviewers did not approve them outright for funding.  CIRM staff, however, did under a new procedure, and the agency's governing ratified the recommendation. 

Lipshutz also appeared before the board along with several patient advocates who made emotional appeals for funding. Lipshutz's research deals with urea cycle disorders, which occur in one out of 8,200 births. Current treatment is arduous and can involve liver transplants.  

Kohn's research deals with sickle cell disease, which afflicts primarily African-Americans. His efforts are aimed at correcting the sickle gene defect in the blood stem cells before transplanting them back into the patient.

A Research Perspective From a CIRM Scholar

The following article was sent to the California Stem Cell Report by Brigitte Angenieux, 32, a postdoctoral fellow at the David Geffen School of Medicine at UCLA. She studies stem cells and brain tumors and is sponsored by a training grant from the California stem cell agency.

Angenieux's work involves the characterization of the biology of brain tumors to develop better and more efficient treatments. Her project consists of elucidating the genes that are important for the formation, the progression and the mechanism of drug-resistance of brain tumors. She also is interested in determining the relationship between neural stem cells and cancer cells.

She received her Ph.D. from the University of Lausanne, performing research involving retinal stem cells. She came to the United States in 2001. In addition to her research at UCLA, she enrolled in a journalism certificate program through UCLA Extension.

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HOPE AND DISILLUSION

By Brigitte Angenieux

LOS ANGELES -- Nick Orozco, 26, a young researcher, works at the University of California, Los Angeles (UCLA), one of the top 20 international universities. Orozco looks at his cell culture dish with a big smile. His experiment worked after three weeks, a small victory, but he has to redo the experiment three more times. This will take another month or so. His daily routine is a battle between hope and disillusion. Nevertheless he faces this reality with steely resolve because that’s the journey a stem cell researcher endures.

“There is a lot of hope in stem cell research, but I don’t think we understand everything. It takes a lot of time, more than what people are often willing to accept,” said Orozco.

Stem cell research makes headlines almost everyday. Doctors go on TV to explain the great potential of this new treatment. President Obama lifted the ban on federally sponsored stem cell research imposed by President Bush because of personal beliefs and ethical issues in the use of embryonic stem cells for research.

Hollywood stars haven’t shied away from the subject either. Michael J. Fox is a big advocate of stem cell research and its use to treat Parkinson’s disease, which he suffers. Recently, some news agencies have reported that the actress Farrah Fawcett, of the TV show "Charlie’s Angels," traveled to Germany to undergo a treatment to fight the spread of intestinal cancer. On April 6, the Fox News website mentioned Fawcett’s stem cell therapy even though it has been denied by the Fawcett's representatives.

Despite regular reports of breakthrough findings, this cutting edge treatment is still complex and obscure. Where are the cures researchers promised the public? Cancer is still not eradicated from the earth. Alzheimer’s patients are still struggling.

Science is not a straight-forward path, experts say. It requires time and multiple trials. There is no set time for each phase of drug development, but industry representatives commonly say it takes about two to eight years to carry an idea from the laboratory to FDA approval for a marketable drug.

“I think it’s a learning process, a trial and error effort,” said Orozco, who did his undergraduate degree at UCLA in the neurosciences and just applied to a medical school program starting in July. “This needs to be worked out before clinical trials.”

A recent case demonstrated that stem cell research should be applied with caution. An Israeli child suffering from a brain degenerative disease went to Russia for stem cell transplantation therapy. Now, several years after the transplantation, the child has developed cancer.

Dr. Meeyro Choe, 32, a pediatric fellow, took the opposite path of Orozco. She worked in a laboratory for two years between college and medical school. After medical school she took a fellowship and decided to give research another try because she “missed basic research.” She’s working at UCLA in a laboratory doing research on stem cells and cancer. As a doctor she is confronted with a dilemma: treating and answering her patient’s needs for a cure but not at the expense of their safety.

Clinical trials take an average of ten years, according to scientists. They involve three different phases, each testing a specific hypothesis. In phase I, researchers test an experimental drug or treatment for the first time to evaluate the toxicity. In phase II, the drug or treatment is given to a larger group (100 to 300 persons) to evaluate the efficiency. In phase III, the drug or treatment is given to a larger group (1,000 to 3,000 persons) to confirm its effectiveness. Then the drug or the treatment is available to the general public.

“Currently, nine out of 10 experimental drugs fail in clinical trial studies because researchers using lab and animal studies cannot predict how they will behave in people,” said Steve Peckman, associate director of The Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA.

Although the research is time-consuming and complex, it remains intrinsic to the future of medicine as well as the aspirations of such physician-researchers as Meeyro Choe.

“With medicine you can treat hundreds of patients, maybe, but with research you can help many more,” said Choe.