Kaiser Healthline: California's Stem Cell Program Short on Cash and Cures

An overview by Kaiser Healthline of California's nearly 15-year-old stem cell research program received attention in California and nationally last month. 

"Despite Failed Promises, Stem Cell Advocates Again Want Taxpayers To Pony Up Billions" said the headline on the article by Ana Ibarra.

Her piece carried both positive and negative comments on the performance of the $3 billion agency, which is running out of cash for new awards. The enterprise hopes voters will approve in November 2020 another $5.5 billion to continue its work.

The article quoted Marcy Darnovsky, executive director of the Berkeley-based Center for Genetics and Society, a longtime critic of the agency, which was created through a ballot initiative campaign in 2004. 

Darnovsky said that if the agency, known formally as the California Institute for Regenerative Medicine (CIRM), is measured against the campaign promises, “then CIRM has been a flop.”  

The agency, however, pointed to its 56 clinical trials, along with the stories of patients who have benefitted from that research, ranging from children who are alive today as the result of experimental treatment to spinal cord injury victims who are seeing their lives improve. 

Ibarra's article was picked up nationally by Salon. Politico noted it in its California newsletter.  The Sacramento Bee, the only daily newspaper in the state capital, published it as well.  

Webinar on Navigating FDA Stem Cell and Regenerative Regulations

Confused about federal regulation of stem cell therapies? That is the question being asked this morning by a Washington, D.C., law firm that plans to try to provide answers later this month.

The firm, Buchanan Ingersoll & Rooney, said it will stage a webinar on Sept. 17 to explain Food and Drug Administration "regulations and enforcement, and how stem cell stakeholders (pharma/biotech companies, healthcare providers) can best comply."

Fees for the session range from $287 to $487. More information can be found here.  

Brain Cells in Space Backed by Millions from the California Stem Cell Agency

UC San Diego video

The New York Times is carrying a piece today about a San Diego stem cell scientist and a project that involves "brain cell blobs" growing "like crazy" in space.  

The researcher is Alysson Muotri of the University of California, San Diego, who is trying crack some of the mysteries of brain development and mental disorders. His space cell project has been supported by $2.1 million from California's $3 billion stem cell agency along with other funding. 

Muotri is a brain organoid man, so to speak. Muotri and his team grew clusters of cells called brain organoids and sent them into space in July with the help of NASA to see how they would develop in zero gravity. 

Carl Zimmer of the New York Times wrote 1,000 words about the experiment. This morning his piece was on the front page of the Times website with this headline: "These brain cell blobs are growing 'like crazy' in space." 

"What, exactly, are they growing into?" Zimmer's article asked. "That's a question that has scientists and philosophers alike scratching their heads."

"As the organoids mature," Zimmer wrote, "the researchers also found, the waves change in ways that resemble the changes in the developing brains of premature babies."

Zimmer quoted Giorgia Quadrato, a neurobiologist at USC who was not involved in the study, on the subject:

“It’s pretty amazing. No one really knew if that was possible.”

The Times piece continued,

"But Dr. Quadrato stressed it was important not to read too much into the parallels. What she, Dr. Muotri and other brain organoid experts build are clusters of replicating brain cells, not actual brains.

“People will say, ‘Ah, these are like the brains of preterm infants,’ she said. 'No, they are not.'"

California's stem cell agency, formally known as the California Institute for Regenerative Medicine (CIRM), has plowed a total of $5.2 million into Muotri's research, which investigates fundamental mechanisms of brain development and mental disorder. 

In response to a query, Muotri told the California Stem Cell Report:

"CIRM funding was used on this last work to optimize the brain organoid protocol. We used this tool in our last two grants, including the one on Zika virus. So, thankfully to CIRM we now have a reproducible and more robust protocol.

"I think the importance and potential impact of this study is quite significant. We can now model neurological and psychiatric conditions that are caused by defects in the network. All previous brain organoid protocols couldn’t get to this level of activity."

Of Muotri's four CIRM grants, two totalling $2.1 million came into play in connection with the space organoids. One of the awards, DISC2-09649, involved Zika and human neurodevelopment. The other, DISC1-08825, dealt with neuroinflammation, a significant component of neurological disorders, including autism, ALS, Parkinson, Alzheimer, lupus, multiple sclerosis and aging.

Muotri's work has led him to co-found a firm called Tismoo, which is developing therapies involving autism spectrum disorder and other neurological disorders with genetic origins.

Muotri's space organoids also triggered a number of news articles. One by Sharon Begley of STAT carried this headline,

"In a first, cerebral organoids produce complex brain waves similar to newborns’, reviving ethical concerns."

Here is a link to a lengthy release from the UC San Diego wth a headine saying,

"AI Algorithm Can’t Distinguish These Lab Mini-Brains from Preemie Babies"

Here is what CIRM had to say this morning about Muotri's research on the agency's blog, The Stem Cellar. 

"These new organoids allow us to explore how new therapies might work in the human brain, and hopefully increase our ability to develop more effective treatments for conditions as varied as epilepsy and autism."

How Muotri might translate brain cells in space into therapies for such things as autism is yet to be determined. But there is little doubt that his latest results will draw increased attention nationally and internationally in the coming months.

(Editor's note: The information about CIRM's blog was not contained in earlier versions of this item.)

Pressures for Stem Cell Profits and Cures: A Case from Japan with Implications for California

A stem cell treatment in Japan for spinal cord injury is raising a ruckus about ethics, efficacy and billion-dollar searches for cures and profits.

The matter involves a therapy called Stemirac and Sapporo Medical University. The treatment is now available to the public in Japan with most of its $140,000 cost covered by Japan's national health insurance program. 

The most recent overview of Stemirac came yesterday on a site called "Undark" in an article written by Amos Zeeberg. In the piece, Arnold Kriegstein, director of the stem cell program at UC San Francisco, called Stemirac  "essentially an unproven therapy."  Bruce Dobkin, a UCLA neurologist, was reported as saying "the results briefly reported in the media may suggest the treatment doesn’t even work."

(Undark's site says it is a "is a non-profit, editorially independent digital magazine exploring the intersection of science and society."  Its publisher is Deborah Blum, a former colleague of this writer at The Sacramento Bee. Blum is now director of the Knight Science Journalism Program at MIT.) 

In the piece yesterday about Stemirac, Zeeberg wrote, 

"It’s arguably the world’s most ambitious approved stem cell treatment and should have been a cause for celebration: a long-awaited breakthrough for the field of regenerative medicine — using modern biological tools to repair the body — and a harbinger of more impressive medicines."

He continued, 

Arnold Kriegstein
UCSF photo

"Instead, the therapy has been met with a heated debate. On one side, many experts have slammed Stemirac’s approval in uncommonly direct terms, saying there isn’t enough evidence to show it is effective or even safe. The treatment went through an expedited approval unique to Japan: After short, small clinical trials that suggest safety and efficacy, regulators can approve stem cell treatments on a conditional basis — allowing use of the treatments for seven years, while sponsors gather additional evidence to support a full approval.

"Critics also say Japan’s approach is far too soft — that early approvals allow patients to take experimental therapies that could be ineffective or dangerous, at a high cost to both patients and insurance providers. 'This is essentially an unproven therapy,' said Arnold Kriegstein, a stem cell researcher at the University of California, San Francisco. 'I’m very surprised this is happening in a country like Japan.'..."

The Undark article continued, 

Bruce Dobkin
UCLA photo

"What’s more, UCLA neurologist Bruce Dobkin told Undark, the results briefly reported in the media may suggest the treatment doesn’t even work. Dobkin pointed to previous trials testing other potential treatments for spinal cord injuries, and the Stemirac findings 'are exactly the results we found in patients in randomized controlled trials — in the control groups,' he said. That is, patients injected with Stemirac seemed to do as well as patients who got placebos in these earlier trials. He says people who have recently suffered spinal cord injuries, like Kusachi, the injured high diver (mentioned in Zeeberg's piece), and the others in the Stemirac trial, often have significant natural improvement over the next several months — exactly the period covered by the trial. It’s possible the patients were simply healing naturally, he says, but without a control group and double-blinding, it is hard to tell."

Undark's article captures many of the issues surrounding the development of stem cell therapies including the pressure to generate results for patients and profits for companies -- not to mention prestige and praise for researchers.

California's $3 billion stem cell program feels that pressure as well. It is running out of cash and would more than welcome a breakthrough in one of its 56 clinical trials -- one that would stimulate California voters to provide more billions for the state's nearly 15-year-old stem cell research effort.

The Search for a Cure for the Bubble Boy Disease: Orchard Therapeutics and the California Stem Cell Agency

Alliance for Regenerative Medicine video

Orchard Therapeutics, a British firm in which the California stem cell agency is directly supporting with $8.5 million, reports that it is "well underway" with its plans for a major facility in the San Francisco Bay area. 

Orchard says that it is on schedule to open the 150,000-square-foot plant in Fremont, Ca., in 2021, according to an article on BioProcess International.  

The move is part of a broad effort by Orchard to commercialize genetic therapies based on research pursued for decades by Donald Kohn of UCLA. California's stem cell research program has pumped $52 million into Kohn's research, which has saved the lives of more than 50 babies in (ADA-SCID) clinical trials.

Kohn has targeted what is often known as the bubble boy syndrome, a rare, fatal immune deficiency disorder (adenosine deaminase-deficient severe combined immunodeficiency -- ADA-SCID).  

UCLA has licensed Kohn's work to Orchard and will receive compensation at some point. CIRM is also slated to receive compensation should a product be developed. Kohn is one of the scientific founders or the Orchard and is a scientific adviser to the firm. 

The BioProcess article last week by Dan Stanton quoted Ran Zheng, Orchard's chief technical officer, as saying, 

“The diseases we target affect patients around the world, which require us to have the infrastructure to deliver gene therapies globally. We are therefore building a commercial-scale manufacturing infrastructure and leveraging technologies that will allow us to deliver our gene therapies globally and in a fully-integrated manner.”

The Fremont facility represents only part of Orchard's presence in California. Ron Leuty of the San Francisco Business Times reported that the firm leases 14,138 square feet in Menlo Park for labs and offices and 4,472 square feet for development labs and offices in Foster City. 

Orchard's stock price closed at $13.67 yesterday. Its 52-week high was $21.64 and the 52-week low was $8.65.

(Editor's note: This item has been altered from an earlier version to be more specific about the number of babies whose lives have been saved in clinical trials involving Kohn's work. The number now exceeds 50.) 

'Tough Lesson' and Stem Cells: More Time, More Money Urged -- Indirectly -- for California's Research

BioInformant graphic

Time and money, hope and hard work -- not to mention death -- were the topics today on the blog of the $3 billion California stem cell agency. 

The blog item involved more than the demise of patients waiting for a stem cell therapy but also the possible demise of the nearly 15-year-old program, unique in California history. 

The research effort, formally known as the California Institute for Regenerative Medicine (CIRM), is running out of cash. By the end of this year, it expects to have no funds for new awards. 

That situation led to a piece this morning on CIRM's  blog, The Stem Cellar. It was a bit of indirect pitch for continued funding by California taxpayers.

"Time and money are always going to be challenging when it comes to advancing stem cell research and bringing treatments to patients. With greater knowledge and understanding of stem cells and how best to use them we can speed up the timeline. But without money none of that can happen."

The article by Kevin McCormack, senior director of communications for CIRM, recapped the history of the agency, created by voters in 2004 through a ballot initiative that set the state off on the largest scientific research effort of any state in the nation. Indeed, as McCormack pointed out, the funding surpassed research budgets of some nations. The catch in California was that no source of funding for the agency was provided beyond the initial $3 billion. 

CIRM noted the high hopes for quick therapies back in 2004. 

"In the early days there was a strong feeling that this was going to quite quickly produce new treatments and cures for diseases ranging from Parkinson’s and Alzheimer’s to heart disease and stroke. Although we have made tremendous strides we are still not where we hoped we’d be. 

"It’s a tough lesson to learn, but an important one: good scientific research moves at its own pace and pays little heed to our hopes or desires. It takes time, often a long time, and money, usually a lot of money, to develop new treatments for deadly diseases and disorders."

McCormack briefly catalogued some of CIRM's progress and the 56 clinical trials in which it has invested, some of which are in the final stage before federal approval of a treatment. 

But CIRM said, 

"The simple truth is that unless we, as a nation, invest much more in scientific research, we are not going to be able to develop cures and new, more effective, treatments for a wide range of diseases." 

The agency is hoping that voters will approve a ballot initiative in November 2020 that will provide $5.5 billion more for stem cell research. In the meantime, it has $71 million to hand out.

Coming Up Next Month: Final Award Decisions by California's $3 Billion Stem Cell Agency?

The California stem cell agency, which is running out of cash for new awards, has cancelled a meeting this week at which it was scheduled to approve funding for more clinical stage research.

The action sets the stage for a full discussion and decisions by the agency board in late September on its last likely research awards unless it receives a substantial infusion of cash. Known formally as the California Institute for Regenerative Medicine (CIRM), the agency was created by voters in 2004 with $3 billion. That has dwindled to $71 million, although $28 million is committed to sickle cell anemia.

CIRM is pinning its hopes for survival on a possible ballot initiative in November 2020 to provide it with another $5.5 billion. 

In response to a question about the status of the meeting once scheduled for this Thursday, Kevin McCormack, CIRM senior director of communications, noted that the last of the clinical stage applications are being reviewed this month. He said,

"There may be more projects to fund than money."

McCormack said,

"We will be bringing all meritorious projects to the board in September to make funding decisions.  In addition, the full board (not the Application Review Subcommittee) must decide whether or not to redirect money to the Translation bucket in order to fund  those that were not funded last month."

CIRM's funding squeeze generated considerable discussion at the July meeting, including appearances by scientists seeking awards. The full transcript of that session can be found here. 

The application review subcommittee is a subset of the full 29-member board, which includes a number of representatives from institutions that receive awards. The subcommittee was created to avoid the appearance of conflicts of interests on the part of the CIRM board. 

September's meeting will be based at the Oakland headquarters of the agency. It is also scheduled to be audiocast live with Internet access. Additional physical locations are expected to be announced for teleconference access. The public can participate in the meetings via the Internet and at the teleconference locations. 

California's $76 Million Bet: Something Called CAR-T, Cancer and Promises

CIRM-funded researcher Saul Priceman of the City of Hope discusses the CART-T frontier, April 2019. Video by American Association for Cancer Research

California's state stem cell agency has now invested $76 million in treatments sometimes described as "miraculous," whose costs can run upwards of $1.5 million. 

The push into the much-heralded CART-T therapy field is part of the agency's effort to fulfill its 15-year-old campaign promise to state voters to turn stem cells into cures. 

The California Stem Cell Report this week took a look at the  CAR-T slice of the agency's $3 billion research pie in the wake of news that Medicare would now cover major portions of the cost of the cancer-fighting technology.

The decision applied to only two specific therapies. But Seema Verma, the top Medicare executive, said CAR-T was
"an important scientific advancement" and would provide help for "some patients who had nowhere else to turn."

Maria Millan, president of the stem cell agency, called the announcement a big step forward. In an email to the California Stem Cell Report, she said,

“We are encouraged by the announcement that the Centers for Medicare and Medicaid will provide coverage for hospital costs related to CAR-T therapies. This is a major step to providing access to these life-saving treatments for patients in need.”

The CAR-T therapies approved by Medicare can run close to $500,000 plus hundreds of thousands more for related costs. One estimate is that total cost of a CAR-T treatment could hit $1.5 million. 

Their medical promise of CART-T is that it's a cure -- not an ongoing treatment, which also can raise total costs exponentially. The idea behind the therapy is that it powers up a patient's immune system to destroy cancer cells in a targeted fashion.  

"Drugmakers note CAR T-cell therapy is designed to be given just once and to be a potential cure for patients who have run out of other options. But not all patients benefit from it and because it is so new, it’s too soon to know whether it will deliver long-term cures," Laurie McGinley wrote in the Washington Post last week. 

California's stem cell agency, formally known as the California Institute for Regenerative Medicine(CIRM), has approved 11 awards involving CAR-T therapies ranging from basic research to clinical trials. The amounts of the awards run from less than $2 million to nearly $20 million, which went to Poseida Therapeutics, Inc., of San Diego, Ca.

The company has received a total of nearly $24 million from CIRM for its CAR-T work. In May, the Food and Drug Administration approved Poseida's CIRM-backed product as an orphan drug treatment for multiple myleoma, a disease that affects 300,000 Americans every year. The company reports that its Phase Two clinical trial for the treatment is now underway.

Poseida's work has attracted the interest of Big Pharma. In March, Novartis pumped $75 million into the company in a fund-raising round that totalled more than $142 million.  (See here for more information on Poseida.)

Last month, in another CART-T venture, the stem cell agency added more millions to an effort at the City of Hope by Saul Priceman, a breast cancer researcher. He told the CIRM board,

"For the past 20 years, City of Hope has focused intensely on developing CAR-T cell approaches for treating the most intractable solid tumors. In the early 2000s, we were the first to demonstrate solid tumor CART-T cell therapy treatment in patients. And recently we were the first to report our remarkable response for patients with glioblastoma."

CIRM directors added more than $9 million to the $1.4 million already provided to Priceman.

In announcing the award, CIRM CEO Millan said, 

“When a patient is told that their cancer has metastasized to other areas of the body, it can be devastating news. There are few options for patients with breast cancer brain metastases (the target of Priceman's research).

"Standard of care treatments, which include brain irradiation and chemotherapy, have associated neurotoxicity and do little to improve survival, which is typically no more than a few months.  CAR-T cell therapy is an exciting and promising approach that now offers us a more targeted approach to address this condition.”

CAR-T is a gene therapy, which has raised some questions about whether it fits within the scope of the stem cell agency, which was created by a ballot measure in 2004, Proposition 71.  

Kevin McCormack, senior director of CIRM communications, said in response to a query, 

"The programs we’ve funded fit into Proposition 71 because (1) HSC (hematopoietic stem cell) derived CAR-T, (2) CAR T’s enriched for TSCM (stem cell) or gene-engineered T cells qualify as a 'vital research opportunity' as outlined in the proposition." 

Here are links to the CAR-T awards by their CIRM application number, which is very useful in searching for additional information on each grantee's research.

Tran1-10258, $5.6 million, Ezra Cohen, UC San Diego; Clin2-10395, $19.8 million, Matthew Spear, Poseida; Clin1-10999, Devon Shedlock, Poseida; Clin2-10248, $12.8 million, Christine Brown, City of Hope; Clin2-10846, $11 million, Crystal Mackall, Stanford; Clin1-11223, $3.8 million, Xiuli Wang, City of Hope; Disc2-11107, $1.4 million, Saul Priceman, City of Hope; Clin2-11574, $9.3 million, Priceman, City of Hope; Disc2-10748, $1.7 million, Scott Kitchen, UCLA; Disc2-11157, $1.4 million, Lili Yang, UCLA, and Clin2-11380, $4.7 million, Theodore Nowicki, UCLA.

City of Hope video

WebMD and the Rising Framework for a $5.5 Billion Stem Cell Request in California

USC researchers Mark Humayun (right) and Amir Kashani,
CIRM-funded scientists. Click here to go to their research video.

WebMD, a heavily used Internet health and medical site, this week assessed the state of the stem cell field in a two-part series that highlighted much of the clinical work backed by California's $3 billion stem cell agency.

The first installment by Kathleen Doheny offered a national overview, declaring that stem cell research has been underway in significant way for three decades. "Where are we now?" was the headline on the article. Perhaps the key sentence declared,

"While proponents say all this groundwork is finally coming to fruition, others call progress slow and plodding."

WebMD is a go-to site for the public when it looks for medical information. In 2016 it reported that it had nearly 180 million unique visitors per month. Today, it says one out of every four Americans uses its site every month.

The series led with work at USC that is being assisted with millions from the California Institute for Regenerative Medicine(CIRM), as the stem cell agency is formally known. It also noted CIRM's 56 clinical trials and its clinical dashboard. 

CIRM grantees were mentioned, including Andy McMahon, Amir Kashani and Mark Humayun, all of USC and recipients of CIRM awards.

The second part of the series, authored by Karen Weintraub, focused on the unregulated and dubious "stem cell" treatments that are the target of both federal and California state regulators.  The headline said, 

"Stem Cell Clinics: Effective or Pricey False Hope?"

One might ask whether readers of the piece are distinguishing between those sorts of sketchy clinics and California's Alpha stem cell clinics, which are very much the pride of the state research effort. 

The WebMD coverage is part of the framework that is taking shape as the California stem cell agency sees its funds coming to an end. It is hoping for a $5.5 billion infusion from voters via a ballot measure in November 2020. How the public perceives stem cell treatments overall and how voters perceive the success of the state effort are likely to be critical in winning approval of more stem cell cash in California. 

'Snake Oil' Stem Cell Clinics Target of California State Regulators Sept. 18

The California State Medical Board said today it will hold a public hearing Sept. 18 to respond to the burgeoning growth in dubious "stem cell" clinics, some of which have reportedly left some patients harmed both physically and financially.

"Snake oil" is what the unregulated clinics are selling, according to Jonathan Thomas, chairman of $3 billion California stem cell agency, which will be invited to appear at the Sacramento meeting next month. 

The clinics have been operating for years nationally, with at least an estimated 1,000 currently in business. California has the largest number. In the past couple of years, the clinics have achieved more notoriety. That includes a "buyer beware" piece this month on HealthDay.

Responding to an inquiry last week by the California Stem Cell Report, Kimberly Kirchmeyer, executive director of the Medical Board, said today in an email that topics likely to be covered at the board's hearing include:

• Best practices guidelines and outreach and education
• Improved informed consent practices
• Adverse event reporting when treatments go wrong
• Other options to be considered by the board

In addition to the stem cell agency, known formally as the California Institute for Regenerative Medicine (CIRM), the board said it would invite the state Department of Public Health. Members of the public may appear as well.  The Medical Board is the chief regulatory agency for physicians.

Here is the full text of Kirchmeyer's statement, which includes a timeline on the board's actions related to the dubious clinics:

"At the July 2018 Board Meeting, the Board was provided a policy that was adopted by the Federation of State Medical Boards at their annual meeting.  The policy contained several recommendations for state boards regarding Regenerative and Stem Cell Therapy Practices.

At the October 2018 Board Meeting Ms. (Denise) Pines, (president of the board), established a Board Task Force on Stem Cell and Regenerative Therapy.   In April 2019, Board staff met with the California Department of Public Health to discuss issues regarding stem cell and regenerative therapy and discussed how the two entities could work together.  The two organizations also discussed some of the issues regarding investigating complaints regarding these practices. 

"On June 27, 2019, the Task Force members met with Board staff to discuss oversight options the Board may decide to pursue to protect California consumers from unapproved and potentially dangerous stem cell products and therapies and next steps.  

"A few options discussed included the development of educational materials, exploring outreach opportunities, and developing best practice guidelines similar to those adopted by the Federation.  The Task Force also discussed the need for some type of guidance for informed consent.  While current law requires notice to patients regarding stem cell therapies, it only requires notification to the patient that the therapy is not FDA-approved and encouraging the patient to consult with their primary care physician. 

"The Task Force believes a more in-depth informed consent may be needed.  In addition, discussion also included the need for adverse event reporting and what would be required for such reporting. 

"It was determined that the Task Force hold an interested parties meeting to receive feedback from consumers, experts, and stakeholders to assist in the development of materials, guidelines and/or to determine if there are additional options that should be considered.  At this meeting, the Board is also going to ask for presentations from the California Department of Public Health and the California Institute for Regenerative Medicine.

"The meeting will be held September 18 in the afternoon (at board headquarters in Sacramento).  If necessary, a second interested parties meeting will be held by mid-November.  The Task Force hopes to have recommendations presented to the Board at its January 2020 meeting.  "You will be able to watch the update on the webcast when it is posted on the Board’s website within the next two weeks.  Here is the link to the page where the webcast will be posted: http://www.mbc.ca.gov/About_Us/Meetings/ "

California Stem Cell Agency's Business Partnering Program and BlueRock Therapeutics

A $240-million deal yesterday involved an East Coast biotech firm that has loose ties to California's nearly 15-year-old stem cell research program. 

The firm is Blue Rock Therapeutics, Inc., a privately held cell therapy company based in Cambridge, Mass.  Bayer owned about 60 percent of the company and picked up the remainder for $240 million in what it called a "major milestone." 

Last year, BlueRock was one of two companies that joined a program of the $3 billion stem cell agency to create a "built-in concierge service for the stem cell space." The agency, formally known as the California Institute for Regenerative Medicine (CIRM), called its new effort the Industry Alliance Program (IAP).

The agency said at the time, 

"The CIRM IAP is designed to give pharma, biotech and VC firms direct access to CIRM’s growing stem cell portfolio. These partners work in the stem cell and regenerative medicine field and will be connected to CIRM-funded scientists working on projects relevant to their interests."

Regarding the deal yesterday, Ben Fidler of Xconomy wrote,

"The deal gives Bayer rights to a company using cells harvested from healthy donors to develop cell therapies for a variety of different diseases—from neurodegenerative disorders like Parkinson’s to heart failure to graft versus host disease. But the buyout is a gamble on an ambitious technology whose first human study, in Parkinson’s, will start later this year."

So far, CIRM has not announced any fresh results from its industry alliance program. 

The California Stem Cell Agency: 'Envy of the World, ' Hopes Too High?

The prestigious journal Nature yesterday published a piece about California's $3 billion stem cell agency that spoke of voids, envy and "double-edged swords."

The opinion piece was written by Jeanne Loring, a San Diego area

Jeanne Loring

researcher who has followed the agency for years and has been one of its beneficiaries($17 million in awards).

Reflecting on the agency's importance, she wrote,

"For the past dozen or so years, stem-cell researchers in California have been the envy of the world."

Creation of the agency, known formally as the California Institute for Regenerative Medicine (CIRM), "essentially guaranteed that the state would become the center of innovation in the field," Loring declared. Its demise would leave a major void, she said.

Loring continued,

"Although its intentions were laudable, CIRM raised the hopes of the public too high. It needed catchy advertising to gain voters’ support. One of its campaign slogans was 'Save lives with stem cells.' Effective advertisements often focus on a promise and downplay shortcomings, such as the time and resources required to advance a stem-cell therapy through clinical trials to market approval. No CIRM-supported therapy has been approved by the US Food and Drug Administration (FDA), resulting in dashed expectations.... 

"Still, fulfilment of the campaign promise is under way. CIRM has granted funding for 56 stem-cell-based clinical trials."

At the same time, dubious and unregulated clinics that peddle stem cell "snake oil" have proliferated across the country, leading the FDA to attempt a belated takedown of some of the enterprises.

The growth of those clinics is part of "the double-edged sword that is CIRM’s legacy,"  Loring said.

"The agency has enabled fundamental science and helped to establish know-how for rigorous assessment of stem-cell therapies. Earlier this year, my colleagues and I started a biotechnology company, Aspen Neuroscience in La Jolla, California, and are raising funds for a clinical trial of a neuron-replacement therapy for Parkinson’s disease. Without the work that CIRM has done to educate investors and researchers, this would have been very difficult. 

"But the agency’s work has inadvertently helped to boost unregulated, for-profit ‘clinics’ claiming, without sound evidence, that cells derived from fat, bone marrow, placenta and other tissues can cure any disease."

Loring said,

"CIRM has regularly denounced these clinics, which existed before the institute’s creation and will persist as long as they can make money. Still, it is easy to understand how public enthusiasm would spill over to those offering quackery."

Loring noted that the agency, which expects to run out of cash for new awards this year, is hoping that voters will give provide $5 billion more via a ballot initiative in November 2020. 

Loring urged rhetorical caution in the ballot campaign.

"We must strike a balance between future potential and current reality when we talk to the public. Researchers should emphasize that even when therapies show promise in mice, they often fail to work in humans. The only way to find out — and to check for safety — is rigorous scientific testing in clinical trials."

"We need to temper public hope," Loring wrote, while regulators, including the FDA and the California State Medical Board, bring the bad actors under control. 

California Stem Cell Agency Backs Breast/Ovarian Cancer, Brain Injury Research and More with $29 Million; $71 Million Left

Saul Priceman of the City of Hope. Priceman received $9.3 million last month from CIRM for a clinical trial for breast cancer. City of Hope video.

The California stem cell agency last month handed out $29 million to finance efforts to develop treatments for traumatic brain injury, ovarian cancer and more, leaving it with about $71 million for new research awards before its cash runs out. 

The nearly 15-year-old agency, known formally as the California Institute for Regenerative Medicine (CIRM), is hoping that a yet-to-be written ballot initiative for the November 2020 ballot will give it a $5.5 billion infusion. The agency began its life in 2004 with $3 billion. 

Fresh figures from the agency show that it has about $43 million available for new awards, not including those involved in a sickle cell anemia effort with the National Institutes of Health.  CIRM's contribution to that program totals about $28 million. The agency is still accepting applications in that program. 

The amount of funds available overall to CIRM could rise as funds come back to the agency as the result of termination of unsuccessful research.

In last month's two-hour meeting, CIRM's board approved five grant applications, but not without more public discussion than has occurred in some past years when the agency was flush with cash. 

Directors talked about priorities, CIRM's portfolio and the vagaries of the scoring process, which is done behind closed doors by out-of-state researchers/reviewers who do not have to publicly disclose their professional or financial conflicts of interest. 

But the meeting also led to a reflection by CIRM board member Jeff Sheehy on the value that CIRM has brought to the field and California. Sheehy is a patient advocate of the 29-member panel. He has been on the board since its first meeting in December 2004 and leads the board's public discussion during ratification of funding decisions by reviewers.

Sheehy told his fellow board members that he had lost his mother to ovarian cancer and knew the "incredibly painful, difficult road" that she walked.  He said that CIRM is providing a new path to a better future for cancer patients and others with dreadful diseases and urged diligence in supporting renewed funding for the agency.  

In formal action, the board approved a $9.3 million investment in a clinical trial for a treatment of breast cancer, the second most common cancer in women. The trial is the 56th in which the agency is involved. The award went to Saul Priceman of the City of Hope. The review summary of his application (CLIN2-11574) can be found here. 

The CIRM panel also approved awards to the following researchers and institutions. The review summaries for all, including applications not approved, can be found here. 

Mark Tuszynski, $6.2 million, UC San Diego, spinal cord injury (no UCSD news release)
Evan Snyder, $4.9 million, Sanford Burnham, ischemic brain injury (no Sanford news release)
Brian Cummings, $4.8 million, UC Irvine, traumatic brain injury (UCI news release)
Mark Humayun, $3.7 million, USC, age-related macular degeneration (no USC news release)

The CIRM news release on the July meeting and awards can be found here. The transcript of the meeting can be found here. 

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Embedding the Power of Stem Cell Therapies: California's Efforts and the Quest for $5 billion More

Everett Schmitt, photo by Meg Kumin

California's $3 billion stem cell agency has financed a lot of research that winds up as dense, inaccessible articles -- at least to the general public -- in costly scientific journals with imposing pay walls.

Sometimes, however, stories of hope and stem cell progress do emerge that are likely to resonate with the state's citizens. They are the folks who voted to create and finance the agency in 2004 and who are expected to be asked again for more billions next year.

One such example involves the cases of Evangelina Padilla-Vaccaro of Corona, Ca., Ronnie Kashyap of Folsom, Ca. From birth they suffered from what is known as the "bubble boy" disease.

Both children were born with severe combined immune deficiency (SCID) that is ordinarily fatal. But as the result of clinical trials that were backed with millions from the stem cell agency, both are still alive today. (See here and here.)

The agency is formally known as the California Institute for Regenerative Medicine (CIRM). It has a blog called The Stem Cellar. Today it published an evocative piece written by the mother of another child with the "bubble boy" affliction. 

In her case, the work that has saved her son's life was not financed by CIRM. But the agency carried her story as a powerful affirmation of the importance of stem cell research, wherever and however it is supported. 

Kevin McCormack, director of communications for the agency, wrote, 

"CIRM's mission is very simple: to accelerate stem cell treatments to patients with unmet medical needs. Anne Klein's son, Everett, was a poster boy for that statement. Born with a fatal immune disorder Everett faced a bleak future. But Anne and husband Brian were not about to give up. The following story is one Anne wrote for Parents magazine. It's testament to the power of stem cells to save lives, but even more importantly to the power of love and the determination of a family to save their son."

Anne Klein's article is just what supporters hope will be embedded in the hearts of voters come November 2020 when the next round of financing for CIRM will be on the ballot. 

These sorts of stories, however, have received little attention in the mainstream media, whose reporting resources are ever-diminishing. The media are hard-pressed financially and otherwise nowadays as their once highly profitable business models have been hard hit by the impact of the Internet. 

Nonetheless the agency is assiduously pumping out information and stories on what it calls its value proposition. Here is the final line in the item that CIRM published today:

"You can read about the clinical trials we are funding for SCID here, here, here and here."

Unregulated Stem Cell Treatments Targeted by California Medical Board; Hearing Next Week

"Snake oil" stem cell clinics in California and their physician operators are on the agenda next week of state medical regulators as deep concerns are being raised in Congress about the slow pace of federal action against the enterprises. 

Last week, a bipartisan group of leaders of a U.S. House of Representatives committee told the Food and Drug Administration (FDA) in a letter, 

"We appreciate the actions taken by FDA, but this pattern of unsafe and unproven therapies remains deeply concerning. Such treatments not only pose public health risks for patients, but also harm the future promise held by the development of stem cell therapy as a field."

California also has been slow in dealing with the issue. State legislation to deal with the matter has been shunted aside.  More than a year ago, the state's Medical Board created a task force to deal with the issue. The panel did not hold its first meeting until June 27 of this year and then with no public notice. 

Experts who follow growth of the dubious clinics say more than 1,000 exist in the United States. The largest number are in California. The treatments are unproven and cost desperate patients thousands of dollars. The clinics have been linked with several cases of blindness and at least 12 serious infections. The FDA has filed lawsuits against two, including one in California, and sent 45 letters to clinics involving their practices. 

The agenda for next week's state medical board meeting says only that an "update" will be delivered by the task force which consists of two members of the board, Randy Hawkins and  and Howard Krauss. No action was specifically listed for the agenda item (No. 21), but the board couches its agenda in such fashion that it could legally act on any matter before it. 

The Congressional letter to the FDA not only expressed serious concern about the proliferation of unproven therapies,  but also said, 

"The advertising strategies some of these clinics employ to attract some of the most vulnerable patients are particularly alarming. Some have advertised stem cell treatments to desperate patients with the most serious untreated illnesses, such as spinal injuries, Parkinson's disease, and multiple sclerosis. Some clinics have misled patients into believing that the therapies they offer are FDA approved or that they are being offered as part of an FDA sanctioned clinical trial."

The chairman of the board of California's $3 billion stem cell agency, Jonathan Thomas, has called the treatments "snake oil." The agency, formally known as the California Institute for Regenerative Medicine (CIRM), is running out of cash. It is worried that a move to refinance the agency via a ballot measure next year could be harmed by voter confusion about the stem cell research.

The congressional letter said,

"When providers offer harmful, unproven stem cell therapies outside of the clinical setting, they create confusion among patients and undermine public confidence in treatments that have been proven to be safe and effective through well-designed clinical trials. If we are to realize the potential clinical benefits of stem cell therapies, it is crucial that developers focus their efforts on the use of traditional developmental pathways that yield definitive results rather than promoting products with 'dubious clinical efficacy and possible risks.'"

Next week's meeting is open to the public. Letters to the board can be emailed to executive director, Kimberly Kirchmeyer, at Kimberly.Kirchmeyer@mbc.ca.gov.

The "Hard Case" of Stem Cell Sound Bites and a Campaign to Raise Billions

The journal Nature today reported on the $5.5 billion plan to save what it called the "struggling" California stem cell agency, which is fast running out of cash for new research awards. 

In an article by Jonathan Lambert, Nature caught up with news that it is not so new to readers of this web site. 

The piece carried information from Robert Klein, who expects to lead a new ballot initiative effort late next year to provide the billions more for the California Institute for Regenerative Medicine (CIRM), as the agency is formally known. 

Nature also had this from a man who served on the Institute of Medicine team that evaluated the California program in 2012.

Aaron Levine, Georgia Tech photo

"Aaron Levine, a science-policy researcher at the Georgia Institute of Technology in Atlanta, says that CIRM has put California at the center of stem-cell research worldwide. 'CIRM has been really important in driving stem-cell research forward, especially in the preclinical and proof-of-concept space,' he says. 

"But he isn’t sure whether that will convince voters to keep supporting the agency." 

The Nature article continued,

"'It will be interesting to see if the campaign is one of promised cures, or something a bit more nuanced,' says Levine. 'It takes time for a whole new field of research to result in cures, but that’s a hard case to make to voters in short sound bites.'"

Nature said Klein told it that he will form a non-profit lobbying arm in October or November to help support the campaign next year. 

The journal also said changes in the stem cell research program were anticipated in the new ballot initiative.  

"These include creating a dedicated staff of 10–15 people who would work with insurance companies and patients to improve access to clinical trials and future therapies."