Friday, August 17, 2018

A California Stem Cell Tale: The Search for a Treatment for Paralyzing Spinal Injuries

Ed Wirth of Asterias, photo by Gabrielle Luri, SF Chronicle 
The San Francisco Chronicle, in a lengthy and dramatic article this week, reported on the story of the first clinical trial in the United States for a human embryonic stem cell treatment, a tale that continues today and well into the years ahead. 

The story involves paralyzing spinal injuries, incurable afflictions, walking rats, Geron, Asterias Biotherapeutics and BioTime and the economics of development of a stem cell therapy. That is not to mention the California stem cell agency, which has pumped more than $20 million into the effort.

The story was written by Erin Allday and is the third installment in a series involving stem cell research and treatments, both legitimate and illegitimate.

Her story began like this:
"Amid the controlled chaos of the operating room, Edward Wirth stood to the side, watching the surgeon slice open the back of the young man on the table....
"The surgeon nudged aside skin and a thin layer of muscle and clamped them out of the way. He chipped away bony vertebrae, exposing the shiny, smooth rope of the spinal cord. His scalpel slid into the membrane surrounding it.
"Wirth stepped forward, just beyond the surgeon’s shoulder, close by for these last steps. The surgical team moved a robotic arm holding a syringe into place. It was loaded with millions of immature support cells that had been meticulously crafted from stem cells, the cells that are the foundation of the human body, able to transform and reproduce indefinitely."
Wirth is a scientist who has been involved with the research since its early days at Geron of Menlo Park, Ca.. He has put in more than 20 years on the effort. Asterias Biotherapeutics of Fremont, Ca., which is associated with BioTime of Alameda, is currently handling the effort to create a treatment for spinal cord injuries.

The $3 billion California Institute for Regenerative Medicine (CIRM), as the agency is formally known, has provided a total of $20.7 million for the effort, first with Geron and now with Asterias.

Allday detailed the ups and downs, financial and scientific, of the research. She peered into the future and wrote that "it will take years to produce a marketable, federally approved therapy -- assuming their research makes it that far."

Nonetheless, she reported,
"Clinical trials like the one run by Asterias are scientists’ most ambitious attempts to harness the potential of what remains an elusive medical marvel. And the work at Asterias exemplifies both the incredible progress that’s been made in stem cell research and the great distance the field has yet to go before life-changing therapies are widely available.
"Riding on Asterias’ success isn’t just the fate of a single company or the careers of scientists like Wirth. Potentially, tens of thousands of patients every year could benefit directly from its therapy — and millions more if its research leads to further advances."
The fourth and final article in the Chronicle series is now scheduled to appear on Sept. 6  and will take a look at the California stem cell agency. Sphere: Related Content

Wednesday, August 15, 2018

California's Stem Cell 'Gold Rush:' Nearly 14 Years of Prospecting

A committee of the California Legislature today examined the state's $3 billion stem cell agency. Officials of the agency and others presented their perspective. Here is the text of prepared remarks by David Jensen, publisher of this blog, who appeared at the invitation of the Legislature.
Sphere: Related Content

Thursday, August 09, 2018

ACT to Astellas: A 'Looping' Tale of the Stem Cell Industry and Research

Ever wonder what happened to Advanced Cell Technology, Inc. (ACT), the Massachusetts stem cell company that migrated -- with some considerable ballyhoo -- to California in the wake of the creation of the Golden State's $3 billion stem cell agency?

ACT landed in the San Francisco Bay area in 2006 with hopes of snagging millions from the agency, which had been created two years earlier. At one point in the company's life, Gov. Jerry Brown even approvingly toured the company's operation in Alameda. But little has been heard from the company in recent years.

Now comes UC Davis stem cell researcher and blogger Paul Knoepfler. Last week, he published a brief update on the doings of the company once known as ACT and its changing corporate identities.

Michael D. West, AgeX photo
But first a little more on ACT's history and the company's not-so-good times in California. It is a tale  that loops around Geron, Inc., which launched and then abandoned the first U.S. clinical trial involving human embryonic stem cells, and companies called
Asterias and BioTime. One thread that strings them all together is a stem cell pioneer named Michael D. West.

When ACT announced its move to the Bay Area, visions of millions of research dollars danced in the heads of its executives. The move was heralded by the state's governmental leaders, Then State Treasurer Phil Angelides said,
"California voters overwhelmingly approved Proposition 71 (which created the stem cell agency) to ensure that California remains the hub of groundbreaking scientific innovation that has the potential to cure and treat debilitating and life-threatening ailments. Advanced Cell Technology's move to California sends a powerful message that this promise can be realized - bringing high-skilled jobs and revenues to our state, and most importantly, offering hope to millions of patients and their families."
West, then president of ACT, said the company was committed to being a world leader in regenerative medicine.

That was in 2006.  Eight years later, ACT, once the only company in the United States with an ongoing clinical trial involving human embryonic stem cells, changed its name to Ocata Therapeutics In 2016 it was purchased by Astellas Pharma of Japan for $379 million. By then, ACT had abandoned its then nominal operations in California after its multiple applications for California state funding failed to win approval (see here and here).

West left ACT in 2007. He is now co-CEO of BioTime, Inc., of Alameda, and is a member of the board of directors of Asterias Therapeutics, Inc., of Fremont, Ca. Both companies are faring much better with the state stem cell agency, formally known as the California Institute for Regenerative Medicine (CIRM).

In 2013, Asterias picked up the human embryonic stem cell trial that Geron gave up on in 2011. West founded Geron in 1990 but left the company in 1998. Asterias has received $14.3 million to support the spinal injury trial that Geron abandoned.

BioTime also had better luck than ACT. It received a $4.7 million award from CIRM for work on human pluripotent stem cells. 

Last week's report from UC Davis scientist Knoepfler said that Astellas began a phase 1B trial in July to continue the macular degeneration work of ACT/Ocata. Knoepfler described the latest effort as a "small bit of encouraging news." Sphere: Related Content

Tuesday, August 07, 2018

California Lawmakers Schedule Update Next Week on the State's $3 Billion Stem Cell Agency

The parents of this child will be testifying next week at a state legislative hearing

For the first time in many years, a California state legislative committee is going to take a look at the state's $3 billion, 13-year-old stem cell research program.

An informational hearing is scheduled for next week, Aug. 15, by the Assembly 
Select Committee on Biotechnology, chaired by Kevin Mullin, D-San Mateo. His district includes a number of biotech firms. No legislation is up for action, and the hearing is not intended to necessarily lead to legislation.

Scheduled to appear before committee are Jonathan Thomas, chairman of the governing board of the agency, and Maria Millan, president and CEO of the agency, formally known as the California Institute for Regenerative Medicine (CIRM).  

The last time a CIRM CEO appeared before a state legislative committee was in 2005 when Zach Hall, then interim CEO testified. 

Also on tap is Jan Nolta, head of the stem cell program at UC Davis, which now stands as the No. 5 recipient of CIRM funds with $138 million. From Folsom will come a couple, Pawash Priyank and Upsana Thakur, whose infant child is now alive as the result of experimental research backed by the agency. The publisher of the California Stem Cell Report, David Jensen, is also scheduled to appear.

The stem cell agency is unique in California history and is a global leader in funding of stem cell research. It operates outside of the normal state budgetary process with its state bond funding flowing directly to it without the usual state budgetary oversight exercised by the governor and the legislature. That is all due to the ballot initiative that created the agency in 2004 and altered the state constitution.

The agency is scheduled to run out of cash next year. It is hoping that voters will approve $5 billion more for it in November 2020.

Next week's hearing, which will be in room 444 in the Capitol, will be available live on the Internet on the day of the  hearing via this page.  It will be archived as well and will be found via this link.

(Editor's Note: An earlier version of this item misspelled the last name of Kevin Mullin.) Sphere: Related Content

Thursday, August 02, 2018

The 'Renegade Outposts' of the Stem Cell Industry: A Sweeping Examination by the SF Chronicle

Chronicle graphic

"Merchants of hope" was the headline today on a lengthy look by the San Francisco Chronicle at what it called the flourishing but costly, unproven and largely unregulated stem cell clinics in the United States and California.

Written by Erin Allday, the piece said,
"They are renegade outposts operating with little legitimacy and oversight at the frontier of what is otherwise a highly promising field of medicine."
It was the second installment in the Chronicle's look at stem cell treatments, both dubious and not-so-dubious. The first was published last month.

Today's piece took a lengthier look at the dubious efforts than has been done in other recent,  mainstream media examinations of the field, which is drawing increasing scrutiny from federal regulators. Allday wrote,
"None of the treatments the clinics offer have been shown to be safe or effective. None have been approved by the FDA. They’re not backed by decades of laboratory and animal studies or by rigorous testing in humans.
"Yet for many patients desperate for care, these clinics fill the void between the long-anticipated potential and the real-world limitations of stem cells. They cater to people whose needs reach beyond the powers of current medicine — people who want to believe in the almost mythic powers of stem cells, who feel corporate health and science have forsaken them.
"People who turn instead to these merchants of hope."
The article also touched briefly on the $3 billion California stem cell agency. Allday said, 
"The California Institute for Regenerative Medicine (CIRM) — the state agency created by Proposition 71 in 2004 to fund stem cell research — has raised concerns about the thriving consumer therapy market. CIRM officials and many of the scientists they fund worry that the selling of unproven treatments could undermine their own work and cast doubt on the enormous potential of regenerative medicine."
Allday continued,
"'It really hurt our recruitment,' said Jane Lebkowski, president of research and development at Regenerative Patch Technologies in Portola Valley. 'We got a lot of questions: What happened in Florida? Am I going to go blind too?'
"Most patients, Lebkowski noted, don’t understand the difference between the fat stem cells that a for-profit clinic is using and the complex product her company is developing, which uses embryonic stem cells to develop a kind of retinal cell that’s damaged in macular degeneration.
"That’s part of the reason why scientists like Lebkowski and organizations like CIRM, which gave $17 million to the Regenerative Patch trial, have pressured the FDA to crack down on the consumer market."
The next installment in the series will deal with stem cell research and is scheduled for publication Aug. 16.
Sphere: Related Content

Tuesday, July 31, 2018

California Stem Cell Cybercast: Multiplying the CIRM Story


Here is today's CIRM Facebook event. The number in the lefthand corner is not static.
It changes as more people view the cybercast.

California's 13-year-old stem cell research agency staged another event in cyberspace today, chalking up more than 1,200 online views for its exploration of the search for cures and therapies for Lou Gehrig's disease.

It was the second go at Facebook Live for the California Institute for Regenerative Medicine (CIRM), as the agency is formally known.

The online event, which features disease experts and questions from viewers, bypasses traditional media and features a concrete way of measuring the event's reach both today and two weeks from today. It could be a significant communications tool for the $3 billion agency, which expects to run out of funds for new awards by the end of next year. The agency is hoping voters will approve another $5 billion in funding in November 2020.

Today's event garnered 819 viewers during its initial hour. By the time of this writing that figure had climbed to 1,262 as others found the event on Facebook.

The first Facebook event for CIRM, which discussed stroke therapy, has now recorded more than 7,500 views. Sphere: Related Content

Monday, July 30, 2018

Live Online Event Tomorrow from California Stem Cell Agency: Ask the Experts about ALS

California's $3 billion stem cell agency tomorrow will offer up a live, online and interactive look at ALS and the research it is financing to help find a cure for the affliction.

The agency has pumped more than $79.4 million into efforts aimed at ALS, which is often referred to Lou Gehrig's disease. Three researchers funded by the agency will be online tomorrow and will address questions from viewers. Here are more details here about the agency's FaceBook Live event at noon PDT, including instructions on how to view it and take part.  Sphere: Related Content

Solomon and Stem Cells: California's Stem Cell Agency Is Slicing and Dicing Cash and Research Decisions


California's stem cell agency gave away $14 million this month, which could be described as less than a drop in its $3 billion bucket.

But the talk at the agency's awards meeting July 19 was not about largess. Instead it was about the lack of cash, lack of time and the need to split "babies" and "buckets."

"We are going to have to make some hard choices today," said one member of the agency's governing  board, Jeff Sheehy, a patient advocate member of the board for HIV.

"We are coming to the end," said another, Oswald Steward, director of the Reeve, Irvine Research Center at UC Irvine.

Sheehy and Oswald and others referred to the shrinking finances of the California Institute for Regenerative Medicine (CIRM), as the Oakland-based agency is formally known. It expects to run out of cash for new awards by the end of next year. Its leaders are trying to raise more than $200 million privately to tide it over until November 2020. That's when they hope another ballot initiative/bond measure will be approved by California voters and pump an additional $5 billion into the 13-year-old enterprise.

That was the backdrop at the session earlier this month. It was a meeting that illuminated the changing criteria that the agency is beginning to use  -- as the cash squeeze tightens -- to make decisions on who and what to finance. No longer will patient advocates or researchers be able to assume that an excellent scientific score assures that an application will be ultimately approved. Instead, "programmatic" considerations will play an important and perhaps definitive role.

Those considerations range from whether a researcher has received past funding from the agency, whether the application fits well within the agency's mission, whether an application fills a void in the agency's portfolio and just how innovative the research is, plus much more.

The discussion about diminishing resources arose when directors were given the usual list of applications that were approved for funding by its reviewers, who met earlier behind closed doors.  Normally, the reviewer decisions are rubber-stamped. This time, however, the 14 reviewer-approved applications totaled $19 million, but only $10 million was budgeted. That's when some directors brought up the need for Solomon-like decisions that would "split" the babies and the "buckets" of cash.

One upshot was that two applicants, James Hagood of UC San Diego and  Vittorio Sebastiano of Stanford, received only partial funding with the expectation that the board would approve a revision in the budget in late October. Nonetheless, those researchers were better off than six applicants who were also approved for funding by reviewers, but not by the CIRM directors. Final action on their applications was put off, probably also until late October.

The $10 million round involved basic types of research, but with a two-year time table. Directors also took action in another, separate round involving preclinical work. It dealt with only one application for $3.99 million, which was approved with no discussion. It went to Poseida Therapeutics, Inc., of San Diego for research aimed at supercharging  "a patient’s own immune system cells to attack and kill a treatment-resistant form of prostate cancer," according to the CIRM news release on all the awards. Poseida matched the award with $998,023.

It was the second CIRM award for Poseida, bringing its total from the agency to $23.8 million.  Here is a link to the summary of comments from reviewers on the Poseida application.

Below is a list of the other approved awards, all of which went to institutions that have links to a CIRM governing board member. Those members were not allowed to vote on those applications. Here is a link to a document which contains summaries of the reviewer comments on each application as well as ones that were not funded on July 



Application number
Title
Institution

Amount
Principal
Investigator
DISC2-11131
Genetically Modified Hematopoietic Stem Cells for the Treatment of Danon Disease
UC San Diego
$1,393,200
DISC2-11157
Preclinical Development of An HSC-Engineered Off-
The-Shelf iNKT Cell Therapy for Cancer
UCLA
$1,404,000
DISC2-11036
Non-viral reprogramming of the endogenous TCR╬▒
locus to direct stem memory T cells against shared
neoantigens in malignant gliomas
UC San Francisco
$900,000
DISC2-11175
Therapeutic immune tolerant human islet-like
organoids (HILOs) for Type 1 Diabetes
Salk Institute
$1,637,209
DISC2-11107
Chimeric Antigen Receptor-Engineered Stem/Memory
T Cells for the Treatment of Recurrent Ovarian Cancer
City of Hope
$1,381,104
DISC2-11165
Develop iPSC-derived microglia to treat progranulin-
deficient Frontotemporal Dementia
Gladstone Institutes
$1,553,923
DISC2-11192
Mesenchymal stem cell extracellular vesicles as
therapy for pulmonary fibrosis
U.C. San Diego
$865,282
DISC2-11109
Regenerative Thymic Tissues as Curative Cell
Therapy for Patients with 22q11 Deletion Syndrome
Stanford University
$865,282
Sphere: Related Content