California Legislation to Curb Unregulated Stem Cell Clinics Due by March

Legislation to help stem the tide of unregulated stem cell clinics in California is still being drafted, but is inspected to be introduced by the end of this month. 

Art Torres, vice chairman of the California stem cell agency, is working on the measure, which is expected to be authored by Assemblyman Kevin Mullin, D-San Mateo. 

More than 100 dubious stem cell clinics are estimated to be in business in the Golden State, peddling ostensible stem cell treatments that cost thousands of dollars.  The treatments, however, have no scientific proof of efficacy or safety. 

In response to a question, Torres, a former state lawmaker, said that Mullin will introduce legislation that will serve as a placeholder while the legal language is worked out and coordinated with appropriate state agencies.

Torres said in an email, 

"We will have the language ready by March 1 , 2019, to be amended into the spot (placeholder) bill. 

"April 26 is the last day that a policy bill with fiscal implications must be out of the policy committee and referred to the fiscal committee."

The clinics and their treatments are a national issue as well involving the Food ad Drug Administration, which has been slow to move. California legislation is likely to serve as something of a model for other states.

Stanford Probe into Researchers Linked to Gene-edited Babies in China

Stanford University is looking into the involvement of several researchers in connection with the Chinese, gene-edited babies, the MIT Technology Review reported today.

The article by Antonio Regalado said,

"Officials at Stanford University have opened an investigation into what several high-profile faculty members knew about a Chinese effort to create gene-edited babies led by a onetime researcher at the California school, He Jiankui. 

"The investigation, according to people familiar with it, aims to understand what liabilities or risks Stanford may have in connection with the controversial medical experiment, which led last year to the birth of two girls whose genomes had been altered with a molecular tool called CRISPR to render them immune to HIV."

Regalado reported, 

"Stanford launched the investigation following media reports that three of its faculty—more than at any other institution—were aware of He’s plans to create the gene-edited children. They are William Hurlbut, a medical ethicist and theologian who interacted extensively with He over many months; gene-editing specialist Matthew Porteus; and Stephen Quake, a biophysicist who holds a powerful role as co-president of the $600 million Chan Zuckerberg Biohub, as well as being He’s former postdoc advisor."

Porteus has received $7.7 million from the California stem cell agency, formally known as the California Institute for Regenerative Medicine (CIRM). He Jiankui worked from 2010 to 2012 in Quake's lab. Quake is participating in a $40 million genomics program backed by the $3 billion stem cell agency.

Quake has declined comment in the past on his connections to He. Porteus told STAT in December that he had "strongly rebuked" the controversial researcher for what Porteus said was "reckless" work.  Hurlbut has said he had a number of conversations with He and advised him on the moral implications of the work.

Regalado wrote,

"University-led investigations are typically private, toothless affairs with few consequences for important faculty, especially those who pull in millions in grants. The question of research involving human subjects is a critical one, however, in part because serious violations can endanger a university’s federal research grants." 

Roman Reed Act: $5 Million Proposed for More Research into Spinal Cord Injury

Roman Reed discusses stem cell research in 2017

Legislation to provide $5 million for stem cell and other research involving spinal cord injury has been introduced in the California state legislature and is expected to be heard soon in a key committee.

Assemblyman Kevin Mullin, D-San Mateo, introduced the measure that would re-fund the Roman Reed Spinal Cord Injury Research Act. 

Mullin, chair of the Assembly Select Committee on Biotechnology,  said in a news release 

“Sadly, efforts to continue this funding stream that expired in 2011 have failed and critical research in this area has suffered. The absence of state funds has limited the programs ability to attract private investment, limiting the work being done.” 

The news release continued, 

"The Roman Reed Spinal Cord Injury Research Act was originally established in 2000 and was subsequently renewed in 2004. The program, based at the University of California Irvine has continued its work, but on a smaller scale. According to the Reeve-Irvine Research Center, the earlier allocations of approximately $15 million in state funding allowed the program to leverage over $80 million in new grants benefitting virtually all California spinal cord scientists."

The legislation is named after Roman Reed, who suffered a paralyzing spinal cord injury in 1994. He and his father, Don, have been longtime backers of the $3 billion California stem cell agency.  Roman Reed came up with the first slogan of the agency, formally known as the California Institute for Regenerative Medicine (CIRM): "Turning stem cells into cures."

A comment by Don Reed wound up as the title of CIRM's  2018 annual report: "Something better than hope." The senior Reed lobbied the legislature for several years to create the act that ultimately provided the funding for the spinal cord research.

The bill is slated to come before the Assembly Health Committee for its first hearing, perhaps as early as this month. 

A Stem Cell Media Story: The Case of the Missing Mention

Storks and stem cell blessings

California's $3 billion stem cell agency, which is fighting to demonstrate its value proposition, this week received what could be considered some favorable attention in the prestigious journal Nature.

The catch is that the 14-year-old research program was not mentioned by name by Nature.

The question is: How does that work and why it is important?

First things first: It is important because the agency, known formally as the California Institute for Regenerative Medicine (CIRM), is hoping that the voters will bless it with another $5 billion come the November 2020 election.

The agency expects to run out of money for new awards this year and is also trying to raise privately more than $200 million to tide it over until the 2020 election. In both cases, it needs clear successes that demonstrate that it has earned its keep and will do even better in the future. 

Unproven Therapies in Japan

The not-so-odd case from Nature involves an editorial that cited a CIRM-funded clinical trial.  Nature praised it as something to be emulated in Japan as an example of good ethics and good science. 

Nature's editorial zeroed in on how Japan has embarked on "a worrisome approach." The headlines said,  "Japan should put the brakes on stem cell sales. Unproven therapies should not be marketed to patients."

Instead, Nature declared that Japan should focus on the approach taken by Asterias Biotherapeutics, Inc., of Menlo Park, Ca., which arguably owes its existence largely to CIRM. (See here, here and here.)  Nature wrote, 

"Last week, a Californian company called Asterias Biotherapeutics released promising results from a 12-month first phase clinical trial, in which embryonic stem cells are converted into oligodendrocytes — cells of the central nervous system that support neurons and can stimulate their growth — and then injected into the backs of people with a spinal-cord injury. The data show that injected cells do stick around at the injury site, and that most patients (21 out of 22) showed improved movement. 

"But these are still early-stage results. It is not clear yet whether the improvements are the result of the cells, or whether something else, such as the body’s own regenerative capacity, was at work. To find out, the company wants permission to move forward with a randomized, controlled phase II clinical trial. That’s the right way to do things: stepping carefully, slowly and rigorously forward."

It's Not the Stork

The problem for the stem cell agency, of course, is that Nature did not identify CIRM as a player in the Asterias effort, although the agency has pumped more than $20 million into the research. The case of the missing mention is not an unfamiliar situation for the agency, which is often not noticed in news and press releases about the scientific accomplishments that it has backed with tens of millions of dollars. 

Of course, CIRM cannot take full credit for the Asterias work. And federal regulators have rules for clinical trials. But CIRM put up the cash for the research after Asterias' predecessor bailed out.  The agency also partners closely with its grantees and has a clear set of pioneering research standards that it worked out more than a decade ago. 

Obviously, CIRM would have been only a brief note, perhaps only a phrase in the Nature editorial if it had decided to include a mention. But these things add up and are needed by CIRM as it tries to tell California voters that it has been worth $3 billion. Their absence can amount ultimately to a substantial negative. 

One does not have to support more cash for CIRM to recognize that California voters need the full array of information about the agency to make an informed decision in 2020. Currently, however, the traditions and practices of scientific journalism regularly omit significant financial information.

When one reads about scientific advances in the mainstream media as well as journals, it seems as if the research magically materializes without a critical insemination of cash -- much like a baby being brought by the stork.

Perhaps it is time for CIRM, other research funding agencies and patient advocates to have a facts-of-life "talk" with the scientific press about the reality of what it takes to give birth to prodigious medical advances.

(Editor's note: Here is a related item by UC Davis stem cell research Paul Knoepfler on the Japanese program.)

California Stem Cell Agency Approves Assault on "Terrorizing" Affliction: Huntington's Disease

Frances Saldana, at a stem cell agency meeting last year, spoke emotionally about the loss of her three children to Huntington's disease. 

Directors of the California stem cell agency this morning approved $18 million in clinical stage research awards, including a "high risk" plan to tackle a degenerative brain disease for which there is no treatment.

Action on the proposal to create a therapy for the genetic disorder, Huntington's disease, came after a woman who lost all of her three children to the affliction said it has "terrorized my family for generations."

Frances Saldana of Fountain Valley, Ca., wept as she pleaded for approval of the $6 million effort to treat the disease that  lingers in her family. 

Another patient advocate, Bill Waddington, whose mother died from the affliction, told the agency in a letter, 

"Huntington’s disease isn’t just death.  It’s complete and utter devastation to families."

Maria Millan, president of the stem cell agency, said later in a news release that children born to parents with Huntington's have a 50/50 chance of getting the disease.

Huntington's affects 30,000 persons with another 200,000 at risk. It  progresses slowly. Symptoms are unrelenting and include inability to control movement and declining cognition leading to dementia, according to experts. Affected persons usually die within 15 to 20 years after diagnosis,. 

The applicant for state stem cell funding, Leslie Thompson of UC Irvine, told the board in a letter,

Leslie Thompson
UC Irvine photo

"Given the relatively slow progression of HD, care-giving stretches over 10 years or more after the patient loses independence. Patients become completely dependent on family and caregivers, who in turn have an emotional and debilitating economic burden managing the physical, cognitive and psychiatric manifestations of the disease.  

"HD can lead to catastrophic events such as homelessness, prolonged hospitalization awaiting placement, or long-term psychiatric placement. The length and severity of the disease has a profound financial and emotional impact on families and health systems. The direct medical costs and costs of disability and care giving for each patient are substantial and pass from one generation to the next."

Members of the governing board of the agency, formally known as the California Institute for Regenerative Medicine (CIRM), discussed the application at some length because of a split involving the application reviewers. The summary of comments by reviewers said,

"Reviewers disagreed on whether the treatment offers a significant value to the patients and caregivers. Some reviewers thought the immunosuppression and surgical risk that is required for this cell therapy may outweigh any potential therapeutic benefits given that there are other less invasive treatment options being tested. Others thought that despite the stated risks, any potential treatment for slowing down disease progression is worth pursuing as current alternative therapeutic approaches are still many years away from commercial use."

Last month, the agency's reviewers, meeting behind closed doors, approved the award on an 8-1-5 vote with five against funding, eight for funding and one saying the application needs improvement and could be resubmitted. The latest application was, in fact, a resubmission after changes were made to deal with reviewers' concerns.  The summary of the latest version described the effort as "high risk."

In one of the six letters of support for Thompson's research, Michael West, CEO of AgeX Therapeutics, Inc., of Alameda, Ca., said the work could have application in treatment of other neurodegenerative diseases such as Alzheimers and Parkinson's.

Six is a relatively high number of letters for the board to receive on an application.  Advocates dealing with Huntington's have been active in the past, appearing before the CIRM board on a number of occasions.

The second award today went to Everett Meyer of Stanford and totalled $12 million. It involves a clinical trial for renal failure. 

Here are links to review summaries for each application considered today, the principal investigator, institution and other information. 

Application number, CLIN1-10953; amount, $6.0 million; title, "An hESC-derived hNSC Therapeutic for Huntington’s Disease;" principal investigator, Leslie Thompson; institution, UC Irvine; review summary; letters of support, letter to the board CLIN1-10953, letter to the board #2 CLIN1-10953,​ letter to the board #3 CLIN1-10953, letter to the board #4 CLIN1-10953, letter to the board #5 CLIN1-10953, letter to the board #6 CLIN1-10953, letter to the board CLIN2-11431, other CIRM funding for the PI, $12 million.

Application number, CLIN2-11400; amount, $12.0 million; title, "Induction of Tolerance by Combinatorial Therapy w/ Donor Stem Cells and Expanded Recipient Treg cells in HLA-mismatched Kidney Transplant Recipients;" principal investigator, Everett Meyer; institution, Stanford; review summary; letters of support, none; other CIRM funding for the PI, none.

Action on the following application was put off until Feb. 21 to provide time to answer financial questions raised by board members today: 
Application number, CLIN2-11431; amount, $6.0 million; title, "A monoclonal antibody that depletes blood stem cells and enables chemotherapy free transplants;" principal investigator, Judith Shizuru; institution, Stanford; review summary; one letter of support; other CIRM funding for the PI, $20.4 million.

California Stem Cell Agency to Award $24 Million for Three Clinical Trials

If all goes according to plan, in just three days the California stem cell agency will be down to its last $69 million for clinical trials.

Directors are set to give away $24 million on Wednesday for three clinical trial programs as the agency runs out of cash this year for new awards. The agency started with $3 billion 14 years ago. It has allotted $144 million for research awards this year.

The agency, known formally as the California Institute for Regenerative Medicine (CIRM), is attempting to raise privately more than $200 million this year. It is also hoping that voters will approve $5 billion more in funding in the November 2020 election. 

Applications coming before directors this week involve $6 million for Huntington's disease, $6 million for immunodeficiency studies and $12 million for renal failure research. 

The agency withholds the names of researchers and institutions involved until directors act publicly.  The agency's reviewers earlier approved the applications during a closed door session. The agency board almost never overturns the decision of its reviewers. 

The public can participate in the teleconference meeting via the Internet. Instructions can be found on the meeting agenda along with summaries of the reviewers comments on the applications.

CIRM was created by California voters in 2004 and provided with $3 billion in bond funding. No other significant source of income was provided under the ballot initiative.

Correction: An earlier version of this item that was up briefly incorrectly described the $69 million as all that remained for all awards this year.    

The Odd Stem Cell Position of the Golden State: Hype, Hope and Dubious Clinics

The California stem cell agency and the Golden State's robust scientific stem cell community received some notice this week in the the Los Angeles Times, the state's largest circulation newspaper. 

It came in the form of an op-ed article that decried the booming business enjoyed by unregulated stem cell clinics, a field where California leads the nation. The Times says it has 1.4 million readers daily and 2.4 million on Sunday.

Usha Lee McFarling, a Pulitzer Prize-winning journalist and currently an artist in residence at the University of Washington, wrote the article discussing the issues surrounding the dubious clinics and their considerable risks, which do not seem to discourage those seeking help. She said,

"So why do patients keep streaming in for treatments that cost thousands of dollars? Part of the reason, I suspect, is that stem cell research — the serious, scientific kind — has gotten so much hype in recent years. We’ve all heard about how some stem cells have the power to become any type of cell in the body and might one day offer cures for all manner of crippling and degenerative diseases. If you can jump the line, and get those treatments now, why not do it? 

"Here’s why: Because the days of miraculous cures, if they come, are far in the future. Today, there is only one federally approved stem cell product: the limited use of blood-forming stem cells to treat certain blood disorders. Scientists are just beginning to learn how to harness the power of stem cells, and the harsh reality is that clinical trials that could turn that knowledge into effective therapies will take years, if not decades."

McFarling continued, 

"California is in an odd position. It is the state with the most stem cell clinics in the country offering these unproven 'cures.' It also happens to be a world center of serious scientific stem cell research, thanks to a $3-billion ballot initiative, Proposition 71, passed by voters in 2004 to fund research."

She noted the fledgling efforts at the state and national level to deal with the dubious clinics. McFarling wrote, 

"Here’s an idea in the meantime. The many scientists who have benefited from taxpayer support of stem cell research in the state should start speaking out. After all, the hype from proponents of Prop. 71 (which created the state stem cell agency) is part of what created such high expectations for quick cures – and eagerness on the part of patients to get them. Scientists should now take every opportunity both to explain to the public the long-term goals of their research and the absurdity of the so-called cures now flooding the market."

Our take: Her advice to California researchers is sound. However, it should be noted that a number of researchers, notably Paul Knoepfler at UC Davis, have been sounding warnings for years. The mainstream media, meanwhile, largely ignored the problem. It took two scientists to do the legwork, which could have been done by journalists as well, that has been the key building block behind the current regulatory efforts, which are still in their infancy.

Is the Governor of California a $5 Billion Stem Cell Friend?

Then San Francisco Mayor Gavin Newsom
 at 2005 announcement of stem cell HQ 
 

California's newly installed governor, Democrat Gavin Newsom, is no doubt a friend of the state's 14-year-old stem cell research program. 

But is he a $5 billion friend?

The question arises because the stem cell agency expects that its funds for new awards will dry up by the end of this year. It is pinning its hopes for survival on a proposed, $5 billion bond measure that may be placed on the November 2020 ballot. And the agency will need all the support it can muster to convince California voters to approve such a measure. 

Newsom's ties to the agency go back more than a decade. As then mayor of San Francisco, he was a key backer of the city's successful effort to lure the agency's headquarters, and he conjured up a $17 million package of incentives. 

He said at the time that the decision to locate the headquarters in San Francisco was a "proud moment." He said the incentive package demonstrated the "city’s unwavering commitment to innovation as scientists search for new methods to treat the world’s most challenging diseases and injuries."

(See here and here for more on Newsom and the selection of San Francisco as the agency headquarters.)

The agency is now based in Oakland. The free rent deal in Newsom's package expired, and San Francisco was too expensive for the California Institute for Regenerative Medicine (CIRM), as the agency is formally known. 

Newsom was busy last week with non-stem cell matters, such as a $209 billion budget he laid out for lawmakers. Given the nature of his and state priorities, he is unlikely to weigh in soon on a tentative ballot measure that is two years in the future. 

Newsom has sounded cautionary financial notes as he proposes ambitious spending plans. Some news stories have highlighted his willingness to pay down the state's debt, which figures into how the stem cell agency operates. 

In 2004, voters created the agency and also approved $3 billion for research awards. Those billions came from debt (bonds) taken out by the state. It is the first instance of a state funding scientific research with borrowed money. 

The interest on the bonds roughly doubles the cost of the agency, meaning a $10 million research grant really costs the people of California $20 million. 

Today, California is flush with cash because of a solid economy and a rainy day fund created by former Gov. Jerry Brown, also a Democrat. Some financial experts and economists are warning, however, that the good times will not be so good in 2020. That could color how voters perceive spending more on stem cell research.

Newsom may also have other, competing spending priorities come November 2020. He may want to husband his political capital to assure their approval. It is exceedingly unlikely, however, that he would oppose a new stem cell bond measure. But he could sit out a campaign for more billions for the agency. 

Given that possibility, maintaining a warm relationship with Newsom likely stands as an important priority for the agency and its backers -- one that they undoubtedly hope demonstrates both the value of stem cell research and the value it brings to the Newsom administration.

The Golden State's Stem Cell Agency Sells its 'Powerful' Story: 2,700 Discoveries, 50 Clinical Trials, Billions Awarded

Ronnie's California stem cell story

"Something Better Than Hope" -- That's the new anthem of California's $3 billion stem cell research program, which is scheduled this year to run out money for new awards.

The 14-year-old stem cell agency trumpeted its new slogan this morning when it released its annual report for 2018. It's a "powerful story," the agency declared on its blog. 

The 28-page document chronicled the state of affairs at the California Institute of Regenerative Medicine (CIRM), as the agency is formally known. The report is titled "Something Better Than Hope. Right Now." CIRM said, 

"While once there was only hope, now we know that cures are imminent."

Kevin McCormack, senior director of communications, celebrated the agency's annual review on its blog, The Stem Cellar. He wrote,

• "50 clinical trials funded to date, 7 this year alone
• "$2.6 billion in CIRM grants has been leveraged to bring in an additional

• "$3.2 billion in matching funds and investments from other sources.

• "1,180 patients have been involved in CIRM clinical trials"

The report itself said,

"CIRM has funded 1,000 projects at more than 70 institutions in California and is the largest single funder in the world of clinical research for stem cell and regenerative medicine. More than 2,700 medical discoveries have been peer reviewed and published in scientific journals. But, most importantly, lives have been saved, second chances have become possible and cures have risen beyond hope."

Stories of the lives of patients in clinical trials were not neglected, including Ronnie, the toddler in the video at the top of this item.

Maria Millan, the CIRM CEO who was a pediatric surgeon earlier in her career, wrote,

"CIRM’s mission is to accelerate stem cell treatments to patients with unmet medical needs.  

"Think about patients like baby Elianna on page 2. She was treated with stem cells for a life-threatening blood disorder while still in her mother’s womb. Ronnie (page 15), who was born with what was previously considered a fatal immune disorder, is alive and thriving today. These stories inspire and motivate us to continue to build upon the great strides CIRM has already made "

The annual report is expected to serve as an important tool as the agency attempts to raise privately more than $200 million to back its efforts until the fall of 2020. That is when CIRM is hoping that California voters will approve $5 billion more for the agency so it can continue its work. 

Annual reports from businesses and government agencies are predictably tilted towards the most positive view of their performance. CIRM's report is no exception. Nonetheless, the agency has run up a record of accomplishment that is significant and important. However, it has not yet fulfilled the expectations of voters in 2004 who were led to believe that nearly miraculous stem cell cures were right around the corner.

Don Reed is a patient advocate who has not lost faith in the promise of stem cells. The California stem cell agency is also indebted to him for his ability to turn the phrase that adorned the cover of the annual report. He was quoted in the report as saying:

"Today, thanks to the 7.2 million voters who authorized the California Institute for Regenerative Medicine, or CIRM, we have something better than hope; we have results, accomplishments, people made well— and a systematic way to fight chronic disease."

California Stem Cell Board Meetings: A Chance to Meet its Directors and Speak to its Staff

The $3 billion California stem cell agency reports that its governing board will meet 12 times this year, mostly in teleconference sessions that will also have access on the Internet.

The business of the board is largely ratifying awards approved earlier by its grant reviewers. However, its financial survival will be a topic of regular discussion this year. The agency expects to run out of cash for new awards before the end of the year. It is hoping that voters will renew its funding with $5 billion in the fall of 2020.

Four "in-person" meetings are scheduled this year during which most of the board will gather at the agency's headquarters in Oakland. They are scheduled to occur in March, May, September and December. Those will be also accessible on the Internet, both for listening or participating.

The meetings of the board offer opportunities for members of the public, including researchers and business representatives, to speak directly to board members and staff of the agency. The in-person sessions are particularly valuable in that regard because of the informality before and after the meetings, as well as during breaks.  Seating is somewhat limited at the meetings at the headquarters of the agency.

Dates and times of the meetings may change, however, and should be double-checked as the sessions near. The first meeting of the year is scheduled to be conducted via teleconferencing and is set for Jan. 30.

The official name of the board is the Independent Citizens' Oversight Committee. The formal name of the stem cell agency is the California Institute for Regenerative Medicine. 

Hype and Fraud and Their Impact on the California Stem Cell Program

Cartoon by Johan Thyberg from "For Better Science"

The New York Times this week published a piece about how the lust for success could be corrupting science in a greater way. 

The questions it raises have particular relevance in the stem cell field, which is still very much in a formative stage. 

Aaron Carroll, a professor of pediatrics at the University of Indiana, produced the opinion piece for the Times. He wrote, 

"How might grant funding and career advancement — even the potential for fame — be biasing researchers? How might the desire to protect reputations affect the willingness to accept new information that reverses prior findings?"

He also said, 

"Moves toward open science, and for a change in the academic environment that currently incentivizes secrecy and the hoarding of data, are perhaps our best chance to improve research reproducibility Recent studies have found that an alarmingly high share of experiments that have been rerun have not produced results in line with the original research."

Questions arise with some regularity about hype and fraud in stem cell research. Back in 2014, bioethicist Art Caplan asked, “Why so Much Fake, Unduplicable Stem Cell Research?”

Just this past fall, a multimillion-dollar stem cell research scandal involving Harvard surfaced once again in the news.

Credibility, of course, is everything in science. For the California stem cell agency, it is a matter of survival. It will be out of cash for new awards in less than 12 months and is hoping voters will then give it an additional $5 billion.  More news about stem cell hanky panky, wherever it occurs, will not serve the agency well when it makes its pitch once again to the people of the Golden State.  

Top Ten Blog Hits by the $3 Billion California Stem Cell Agency

The California stem cell agency produces a blog called "The Stem Cellar," which regularly features fine pieces on stem cell matters in general as well as articles about its own activities.

This week the agency produced a list of the most popular postings on its site. Here is the rundown on the top 10.

• "New stem cell treatment for ALS may slow disease progression
• "Can stem cell therapies help ALS patients
• "Stem cell study holds out promise for kidney disease
• "Your guide to awesome stem cell conferences in 2018
• "Young man with spinal cord injury regains use of hands and arms after stem cell therapy
• "jCyte shares encouraging news update about clinical trial for Retinitis Pigmentosa
• "Stem cell patch restores vision in patients with age-related macular degeneration
• "The 10 most popular stem cell stories of 2017 (is that cheating to include a story about the most popular stories of 2017 in a blog about the most popular blogs of 2018?)
• "Could stem cells help beat multiple sclerosis
• "One-time lasting treatment for Sickle Cell Disease may be on the horizon according to new CIRM-funded study"

Serious Infections and Fecal Contamination Alleged; Feds Battle Rising Tide of Dubious Stem Cell Clinics

The federal government last week stepped up its efforts to curb dubious stem cell clinics, declaring that 12 persons have been hospitalized for infections as the result of treatments involving a San Diego firm.

Some of the products from the firm have been found to have been contaminated with fecal bacteria . 

The federal action (see here and here) comes after years of ignoring the problem, both by the Food and Drug Administration and state regulators. Meanwhile, the growth of unregulated clinics as multiplied. Current estimates are that as many as 700 or more clinics exist in the United States, compared to at least 570 in 2016. 

California has the biggest share of the clinics, which is not unusual since it is the most populous state in the nation. Legislation backed by the California stem cell agency is expected to be introduced in California next month to step up regulation of dubious clinics.

The federal enforcement action came in the form of a "warning" letter from the FDA and involved a firm called Genetech (no relation to the well-respected biotech firm Genentech, but obviously a name designed to lure unsuspecting patients.)

The FDA said 12 patients have contracted serious infections as the result of injections involving Genetch procedures and products. The Center for Disease Control has reported that some of its unopened products contain E. coli and E. faecalis.

Genetech has not responded to multiple efforts by media to obtain a comment on the federal action.

Some stem cell scientists, most prominently UC Davis researcher Paul Knoepfler, have warned repeatedly for years about the unregulated treatments. In addition to the harm to patients, they have noted that the activities of the dubious clinics damage the reputation of the field in general. (See here, and here and here.

A Deep Probe by STAT into the Man Behind the CRISPR Babies

Want to know more about the researcher who spawned what are now known as the CRISPR babies? 

STAT published a cracker jack of a piece this morning about He Jiankui, including details about his life and his pathway into the gene editing game.

STAT promoted the article this morning in a newsletter with this squib:

"Every superhero, and antagonist, has his own origin story. He Jiankui, the scientist who stunned the world with a claim that he had already gene-edited two baby girls, has one too." 

The lengthy article was written by Sharon Begley and Andrew Joseph and covers He's path from physics to biology. They quoted UC Berkeley scientist Jennifer Doudna as saying, 

“His demeanor was an odd combination of hubris and naivete. He was very confident in his work, and not totally understanding what an explosion he had caused.

The STAT piece is based on extensive reporting. Its authors wrote,

"With details reported for the first time, it describes the many times He met with and spoke before some of the world’s leading genome-editing experts, the low opinion they had of his research, and the hints he dropped about his grandiose aspirations. It is based on interviews in Hong Kong and with experts on four continents, with scientists and others who have crossed paths with He, as well as on documents and published accounts. He did not reply to requests for an interview."

The article's final paragraph ends like this:

"Even those who condemn his experiment doubt it will be more than a speed bump on the road to editing of embryos to prevent severe inherited diseases. 'We have to acknowledge there is interest in using [CRISPR] clinically,' Doudna said. To those calling for a moratorium or an outright ban on such research, she has one response: 'It’s too late.'"

California Stem Cell Agency Scores 50 Clinical Trials, Says It "Just Getting Started"

OAKLAND, Ca. -- California's ambitious stem cell agency this morning chalked up involvement in 50 clinical trials, an achievement that was regarded by some as unattainable 10 years ago.

The watershed event came when directors of the agency approved a $6.2 million proposal to help fight lymphoma.
Following the action, the first person ever to participate in a CIRM human embryonic stem cell trial, Richard Lajara, praised the efforts of the agency, which is running out of cash. 

He said the people of California have a responsibility to move forward with stem cell research and to continue to fund the agency. Lajara's appeal followed a statement from the agency that 35 persons are alive today because of clinical trials that it has helped to finance.

Lajara, who is paralyzed from the waist down, was enrolled in 2011 in the spinal injury trial initiated by Geron, Inc.,  and backed by the agency. 

Jonathan Thomas, chairman of the agency, which is formally called the California Institute for Regenerative Medicine(CIRM), said in a statement,

"We have come a long way in the past seven and a half years, helping advance the field from its early days to a much more mature space today, one capable of producing new treatments and even cures. 

 "But we feel that in many ways we are just getting started, and we intend funding as many additional clinical trials as we can for as long as we can."

In the early days of the agency, Robert Klein, its first chairman, and others widely regarded major participation in clinical trials, especially phase three, as largely beyond the financial capability of the agency. The cost was prohibitive, they said.

The cost of trials varies widely but can run into hundreds of millions of dollars, which could rapidly devour the $3 billion the agency had to spend, the reasoning went. Clinical trials are the last stage before a treatment is approved for widespread use by the federal government.

CIRM's first strategic plan in December 2006, which covered a 10 year period, anticipated some involvement in phase one and two trials. But it said,

"Because of their expense and because of the time required to reach this stage of clinical development, CIRM is unlikely to fund Phase III trials over the time span of the strategic plan."

The first patient to enroll in a CIRM clinical trial did not come until late 2011. 

Today, the agency has committed $541 million to clinical trials, including four that are in phase three, the ultimate trial hurdle to clear before a treatment wins approval. The phase three trials involve kidney disease and ALS.

The 14-year-old agency is now down to its last $144 million. Money for new awards will run out at the end of next year. CIRM is pinning its hopes for continued life on a proposed $5 billion ballot measure on the November 2020 ballot.

Key to winning approval would be a favorable result from its clinical trials -- one that would resonate with the voters. Their expectations were raised in 2004 by the ballot campaign that led to creation of the agency. However, the agency has yet to produce a stem cell treatment that is widely available.

Trump, Fetal Tissue and the California Stem Cell Agency

The California stem cell agency says the Trump Administration moves against research involving fetal tissue have had no impact on the projects that it is financing, at least so far.

The agency, formally known as the California Institute for Regenerative Medicine (CIRM), was responding to a question originally raised by a reader of the California Stem Cell Report.

The inquiry was triggered by a number of reports over the last few months concerning the federal direction away from fetal tissue, a move that one researcher, Warner Greene of the Gladstone Institutes in California, called "scientific censorship of the worst kind."

The California Stem Cell Report queried CIRM yesterday about the federal actions, asking whether they have had "any impact, direct or indirect, on CIRM awards, existing or likely in the future."

Kevin McCormack, senior director for CIRM communications, replied, noting that the federal move is relatively recent.

"It could mean an increase in applications that use fetal tissue but it’s too soon to tell. Regardless, this is why the people of California created CIRM, so we don’t have to worry about federal funding for potentially life-saving research. Because we are independent, we can fund what we think is the best science."

McCormack alluded to the ballot initiative in 2004 that established the agency. The campaign was largely based on the need to bypass the Bush administration's restrictions on stem cell research. The anti-fetal tissue effort is likely to be the first step towards resurrecting similar restrictions on stem cell research. 

Politically and ironically speaking, new federal restrictions on human embryonic stem cell research could build support for continued funding of CIRM, which is hoping for passage of a proposed $5 billion bond measure on the November 2020 ballot.

While fresh restrictions are not good for the field overall, their imposition could help to preserve the stem cell agency. Any ballot campaign needs a nasty villain to campaign against.

And without Bush to campaign against in 2004, the stem cell agency probably would never have come into existence.

Here are links to a few of the recent stories on the Trump fetal tissue move: Washington Post, Science, STAT.

Walking a Thin Line at the California Stem Cell Agency

California's stem cell agency has a delicate dance to perform as it edges closer to seeing a $5 billion measure on the ballot to provide more funding for its efforts.

The dance involves a prohibition on state agencies spending public money on behalf of bond measures. The $3 billion agency has a legitimate responsibility to keep the public informed about its activities, but when does that task step over a legal line? 

CALmatters, an online news site devoted to state government matters, touched on the issue this morning. Dan Morain, the site's senior editor, wrote about a couple of cases in the last election.

In his morning newsletter "What Matters," he cited a tiny fine imposed on the Bay Area Rapid Transit District and another case involving an $800,000 expenditure by Los Angeles County board of supervisors, which is unresolved.

As for the stem cell agency, it is certain to be accused of using public money to support any ballot measure that may emerge in 2020. 

That would be part of the political tactics of opponents to the measure -- a portrayal of the stem cell agency as unworthy of voter trust.

The agency is treading lightly in this area right now, a position that will serve it well as more clarity emerges on whether a ballot initiative will actually surface on the November 2020 ballot. 

California Setting Stage for Crackdown on Dubious Stem Cell Clinics

The California stem cell agency, state regulators and lawmakers are taking aim at the more than 100 dubious, unregulated "stem cell" clinics now operating in the Golden State.

The goal is to curb clinics that are using what they describe as stem cells in treatments costing thousands of dollars but that have not been tested  scientifically. Lawsuits have been filed around the country alleging damage to patients that includes blindness.

Art Torres, vice chairman of the state stem cell agency, is now  working with lawmakers to formulate legislation that is expected to be introduced by the end of January.

At the same time, the State Medical Board, which licenses and regulates physicians, has chartered a task force to look into the the growing business.

Earlier this fall, Torres told the governing board of

Kevin Mullin, LA Times photo

the California Institute for Regenerative Medicine (CIRM), as the agency is formally known, that he was engaged with Assemblyman Kevin Mullin, D-San Mateo, on a bill.

Torres, a former state lawmaker, said the legislation is expected to involve certification of clinics by a state department. He said, 

"It involves a number of issues which we (CIRM) really can't be involved with in terms of licensing, but we certainly can be involved with the parameters and the distinctions that we ought to raise as to what constitutes an appropriate stem cell clinic in California."

The Medical Board is scrutinizing the promotional practices and harm caused by the clinics with the intent of crafting regulations to curb abuses.  

The board's starting point is a report by the Federation of State Medical Boards, which says,

"There is reasonable concern about a growing number of providers and clinics in the United States that are undermining the field. Such providers and clinics have been known to apply, prescribe or recommend therapies inappropriately, over-promise without sufficient data to support claims, and exploit patients who are often in desperate circumstances and willing to try any proposed therapy as a last resort, even if there is excessive cost or scant evidence of efficacy."

Paul Knoepfler, a UC Davis stem cell scientist who has long been involved in examination of dubious clinics, has reported that at least 100 such clinics exist in California. 

Writing on his blog Nov. 30, Knoepfler said,

"Broadly, it may be going rapidly from the best of times to the worst of times for unproven stem cell clinics in the U.S., which would be a very good thing for patients and the stem cell field, if it actually happens. We’ll see."

Former Biotech Maven Steve Burrill Sentenced to Prison

Famed and legendary he was called. Now he is facing 2.5 years in prison.

Steve Burrill, wn.com photo

He is Steve Burrill, who once was a featured life science maven/financier/visionary at international conferences such as BIO, which attracts upwards of 16,000 persons annually. Burrill also conducted a well-attended stem cell conference in San Francisco that showcased California's stem cell agency shortly after it came into existence.

Burrill, who was based out of San Francisco, was sentenced this week for defrauding investors and falsifying his tax returns. He pled guilty to siphoning off $18 million from his companies.

Here are links to the news stories on the case: GEN News, STAT, Xconomy.

California Stem Cell Agency Slated to Award $6.2 Million to Fight Lymphoma

California's $3 billion stem cell agency, which turned 14 last month, is expected next Thursday to give away another $6.2 million as it continues its efforts to fulfill the expectations of the voters who created it in 2004.

Also possibly on tap is an update on the status of efforts to raise privately some $200 million to tide over the agency as it looks forward to 2020 and a possible ballot measure to provide it with another $5 billion.

Known formally as the California Institute for Regenerative Medicine (CIRM), the agency expects to run out of cash for new awards in about 12 months. Its award budget for 2019 now stands at $144 million. Presumably, another $28.4 million can be added, which is the uncommitted cash for research left over from this year. 

The agency subsists on state bond funds approved by voters. Its bond issuance authority, however, is expiring. No other source of funding was provided by voters, and the agency has no expectations of being financed on annual basis by the legislature.

The 2004 ballot campaign that created the first-ever such agency in California history raised high hopes a stem cell therapy was right around the corner. CIRM has not yet backed a treatment that is available for widespread use. However, it is helping to fund 49 clinical trials, the last steps before a treatment is approved for the marketplace.

The application (CLIN2-11371) before the board next week has already been approved by the agency's reviewers. Normal practice is for the board to ratify in public earlier decisions made in private by reviewers.

The name of the recipient has been withheld by the agency until after ratification, as is the agency's standard practice. The proposal seeks to continue a phase one clinical trial  to help treat lymphoma.

The CIRM summary of the review of the application said the goal of the research is to "ameliorate or accelerate recovery from toxicities related to high-dose chemotherapy followed by HDT-ASCT for the treatment of lymphoma and other cancers."

CIRM said the method would involve "genetically engineered CD31+ cells derived from human umbilical vein tissue (engineered HUVEC)."

"There are currently only a few moderately effective treatments available to reduce the toxic side effects associated with aggressive cancer treatments – hence a high unmet medical need. New approaches are urgently needed to both improve quality of life and reduce the risks of high dose therapy."

The summary said that the $6.2 million award would be backed by $2.7 million from the recipient.

CIRM Chaiman Jonathan Thomas has been working to raise the private funds to help support the agency beyond next year. He often reports on his progress at board meetings.

The CIRM board meeting will be based in Oakland. Offsite locations where the public can participate are located in Stanford and San Francisco. The public can also log in online and ask questions or make comments. Instructions on how to participate are contained on the meeting agenda. If you are not familiar with the procedure, it is useful to log in about 10 minutes prior to the meeting's start (10 a.m. PST)  to avoid technical difficulties.