Wednesday, June 20, 2018

Safety and Effectiveness Concerns Raised about $5.8 Million California Stem Cell Research Proposal for Parkinson's

A California stem cell scientist yesterday commented on an application before the state's stem cell agency for $5.8 million for research into a possible therapy for Parkinson's disease, which afflicts as many as 10 million persons worldwide.

Jeanne Loring, director of the Center for Regenerative Medicine at the Scripps Research Institute, made the remarks concerning a proposal that is likely to be approved June 28 by the governing board of the $3 billion agency.

Her comments came in an email to the California Stem Cell Report after it asked for her thoughts on the review summary of the application (CLIN1-11059), which has been already approved behind closed doors by the agency's scientific reviewers. The vote was 9-6-0 with nine reviewers voting to approve it and six reviewers saying it needed improvement and should be resubmitted. No reviewers voted outright against it. The summary of the review and application can be found here. 

The name of applicant is not known. The stem cell agency withholds the identity of applicants until an application is ratified by the full board in a public session.

As Loring notes in her email, she is also conducting research on Parkinson's and also has funding from the stem cell agency, formally known as the California Institute for Regenerative Medicine. Here is the text of her email along with links to the two research papers that she cites.

“Researchers have explored many approaches to treatment of Parkinson’s disease over the last several decades. The tremors and freezing in PD are caused by the progressive loss a specific type of dopamine-producing neuron in a part of the brain called the substantia nigra. Half of these neurons have died by the time the disease is diagnosed.

“The only approach that has resulted in long-term reversal of the symptoms of PD is transplantation of human fetal tissue containing the precursors of that specific type of dopamine neuron. 

“The therapy that we are developing is based on the success of those fetal studies; our particular approach is to use patient-specific dopamine neurons produced from their own induced pluripotent stem cells (iPSCs). The arguments in support of this therapy have been published (see below).

“We share this idea for neural replacement therapy with several other groups worldwide: Roger Barker in the UK, Malin Parmar in Sweden, Jun Takahashi in Japan, and Lorenz Studer in New York are using human embryonic stem cell-derived neurons or unmatched iPSCs. We are the only group among these that is using matched neurons so there will be no need for immunosuppression.

“These are my concerns about any therapy using undifferentiated neural stem cells and gene therapy:

“Safety concerns:

“Neural stem cells are dividing cells that have been known to make tumors; one patient in California had a tumor grow in his spine after receiving neural stem cells from a clinic that did not have FDA approval, to treat a stroke. A few years ago there was a proposed treatment for Alzheimer disease that used neural stem cells, and in that case there was clear evidence that those cells made tumors in animals; it was funded by CIRM. Our cells are not dividing, and we have done a one-year study in rats to make sure no tumors form.

“Addition of a transgene for a neural growth factor, GDNF, to the cells, will require thorough testing because transgenes can disrupt the genome, and the expansion of the cells increases the risk of other mutations arising, such as the p53 mutations that we discovered in hESCs a few years ago. p53 is a very bad actor; mutations in this gene are found in half of all cancers. The applicants should be planning to sequence the genome of the cells to be improve the chances that the cells are safe; we sequence our cells.

“Effectiveness concerns:

“Survival vs. replacement.

“There are two general approaches to cell-based treatment of Parkinson’s disease. The neural stem cell approach is not intended to REPLACE the dying neurons. It is intended to help the remaining dopamine neurons survive longer. The other approach, neuron replacement therapy, can reverse the symptoms long-term.

“Immunosuppression. It is necessary to suppress the immune system whenever a transplantation of unmatched cells or tissues is performed. Immunosuppression is a concern for neurologists who are treating PD patients, because it weakens the immune system and makes patients more susceptible to serious debilitating infections.

“The neural stem cells making GDNF may be a good solution for the debilitating neuronal loss in ALS, and CIRM is already funding their use for that disease. But please ask a few neurologists what they would advise their patients with Parkinson’s disease. Those I’ve asked would prefer replacement of dopamine neurons, rather than a treatment using transplantation of dividing cells pumping a nerve growth factor into the brain, that requires immunosuppression. Historically, this has not been a good idea.”

Here are two links to articles that Loring cited. See here and here. 

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Monday, June 18, 2018

California Stem Cell 'Renewal:' The Search for More Billions -- And Credit for Results

A KTVU video connected to CIRM's research support

California's 13-year-old stem cell agency, which is facing its demise as it lingers in a dim media shadow, last week snagged some credit for the work it has helped to finance in saving the life of a five-year-old girl. 

The news story appeared on San Francisco Bay Area television station KTVU. The piece involved Evangelina “Evie” Padilla Vacarro, who was born with what is known as the "bubble baby" disease. That is a genetic affliction that compromises the immune system so severely that it is nearly impossible for a person to survive.

Evie's story is powerful and well-known among those who closely follow the $3 billion California Institute for Regenerative Medicine (CIRM), as the stem cell agency is formally known. But it has not seeped in the consciousness of California voters, who are likely to be asked to cough up $5 billion more for CIRM.

The agency expects to run out of cash by the end of next year. It is pinning its survival hopes on a private fundraising drive underway this year and passage of a proposed bond measure in November 2020. However, many competing priorities exist for that sort of funding. Plus the agency has yet to fulfill voter expectations that creation of the agency would lead to a stem cell treatment that would have widespread use.

In Evie's case, the treatment is available under exceedingly limited circumstances, like other treatments that the agency is supporting. They are still being tested before the federal government approves them for wider use.

The positive results that are, in fact, surfacing often do not mention CIRM's substantial backing, or they bury that fact so deeply it is all but invisible. (See here, here and here.) That is occurring despite the fact that many of those stories emerge from institutions that have received tens and tens of millions of dollars from the agency.

The fresh news peg for the KTVU story last week was the launch of a book, “California Cures: How the California Stem Cell Program is Fighting Your Incurable Disease," by longtime stem cell patient advocate Don Reed. The station reported,
"'Lives have been saved, and suffering eased, because California stood up for stem cells in 2004,' Reed said. 'Now as we approach the end of that (2004) voter-approved program, it is vital that everybody knows the story of (the institute) and why we must renew its funding.'"
Whether that "renewal" actually takes place may depend on whether the researchers and institutions that have benefited from CIRM's largess do a much better job of selling what they believe are the benefits and importance of the agency's programs and cash.
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Saturday, June 16, 2018

CIRM Board Member Sheehy Exiting as San Francisco Supervisor; Says SF Voters Favorable on Stem Cell Work

Jeff Sheehy, a member of the governing board of the $3 billion California stem cell agency, will be leaving his fulltime post as a member of the San Francisco board of supervisors later this year, but he says his unsuccessful election campaign disclosed favorable perceptions of stem cell research.

Sheehy disclosed his plans not to seek re-election in the media in the Bay Area. In a statement, he said it was "immensely rewarding" to have served the city. He also had this to say yesterday to the California Stem Cell Report,
"I have been asked about the implications for CIRM (the stem cell agency) and, based on polling around my bio that my campaign conducted, stem cell research remains very popular.
"When we asked voters about what prior work of mine resonated with them, the tagline, 'Fights for stem cell cures for deadly diseases and conditions as a founding board member of the California Institute for Regenerative Medicine,' was one of, if not the most popular items listed in my background.
"I had multiple conversations with voters about our work at CIRM and they were very supportive and very impressed with the what we have accomplished."
Sheehy is a patient advocate member of the stem cell board and has served on it since its inception in 2004. He is also chair of the Science Subcommittee of the board, participates in closed door reviews of applications for funds by scientists and oversees board discussion of the reviewers' decisions.

Sheehy's term on the 29-member board expires in 2020. The agency expects to run out of cash for new awards by the end of next year, 2019.
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Friday, June 15, 2018

CRISPR, the Cancer Question and the California Stem Cell Agency: $13.5 Million Investment in Eight Projects

CRISPR was in the news this week, and it wasn't about how you like your French fries cooked.

CRISPR, for those of you who don't know already, is a relatively easy way to edit genes. The technique is used in at least eight research projects backed by the California stem cell agency, totalling about $13.5 million.

What made CRISPR generate the headlines was research -- as Business Insider reported -- that the "blockbuster gene-editing tool has been linked to cancer." The assessment was described as hype by some scientists.

Paul Knoepfler, the peripatetic stem cell blogger and researcher at UC Davis, explored the implications of the findings in an item earlier this week. He wrote,
"To say that CRISPR-Cas9 gene editing might 'cause cancer' seems premature to me so there probably were and are better ways for people to phrase the big-picture meaning of these new papers and others like them that may pop up in the future. However, to be clear safety is crucial, so this is an important development and risks of any potential therapy including gene editing-based approaches should be carefully weighed against potential benefits as trials are designed and then progress."
The California Stem Cell Report asked the agency, which monitors the research it funds, for a list of its projects involving CRISPR. Here is what the agency provided, including the disease focus, principal investigator and grant number.
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Thursday, June 14, 2018

Not a Dr. Ruth Explainer: California Stem Cell Agency's FAQ

Looking for a reasonably straight forward primer on the $3 billion California stem cell agency, a state program that is unique in California history and now in its 13th year of life? 

The agency, formally known as the California Institute for Regenerative Medicine (CIRM), has compiled an FAQ (frequently asked questions) list which is available on its web site. Obviously, some of the material is colored by agency's own perspective, but the basic facts are there in one handy document.

The questions deal with such things as "when will there be cures," "shouldn't private industry fund stem cell research" and "what happens when the money runs out."  It's not exactly a Dr. Ruth's guide to all things CIRM, but many may find the document helpful. Sphere: Related Content

Wednesday, June 13, 2018

Fire, Fury and $5 Billion: A Mini Preview of a Ballot Campaign for the California Stem Cell Agency

California's stem cell research effort, which is pinning its survival hopes on a proposed $5 billion bond measure in a couple of years, was slammed in a national publication last week as a "multi-billion dollar money suck."

The column in the conservative magazine National Review, which has about 90,000 circulation and a significant online presence, was a tiny preview of the fire and fury that is likely to erupt around the likely pitch to California voters in 2020 to give more cash to the agency.

Formally known as the California Institute for Regenerative Medicine (CIRM), the agency was created by a ballot initiative in 2004 and backed with $3 billion in state funds. It expects to run out of money for new awards by the end of next year.

Wesley J. Smith, a longtime critic of the agency, wrote in the National Review piece,
"The mendacious (2004) campaign promised Cures! Cures! Cures! with embryonic stem cells and therapeutic human cloning — even promising that disabled children would get out of their wheel chairs and walk. Good grief, campaigners also claimed that the money earned from all the coming cures would reduce California’s health-care budget.
"Some $2 billion later, none of it came to pass. Tens of millions were spent on a fancy-dancy building. Conflicts of interested have abounded. But the supposed point of the CIRM was not achieved. There have been extremely few human trials with embryonic stem cells — mostly dealing with eye conditions — and not all were CIRM-funded."
It is fair to say that Smith's characterizations omit much information about what CIRM calls its value proposition. Nonetheless, his points are likely to resonate with a substantial portion of California voters, who have seen little mainstream media coverage of CIRM. 

Even the institutions and recipients of multi-million dollar research awards regularly fail to note CIRM's contributions in their news releases about state-backed scientific discoveries. (See here and here.)

As of today, the agency has invested in 49 clinical trials, the last stage before a therapy is approved for widespread use. A discovery or treatment that would captivate the public could emerge from those trials between now and the election in November 2020. Meanwhile, given the nature of today's financially struggling media and limited science coverage, the agency and its backers are likely to find it tough to break through the news clutter and convince voters to cough up more cash.   
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Sunday, June 10, 2018

'Spontaneity' Live: A Powerful, Cyberspace PR Tool for California's Cash-Strapped Stem Cell Program?

Jeanne Loring, right, on a Scripps Research Institute
Facebook Live event last week.   Click here to go to the video
Stem cell researchers rarely have a chance to talk directly about their work to thousands of people at a time, including those in the farthest reaches of the globe.

But Jeanne Loring at the Scripps Research Institute did it last week. The California stem cell agency did it last month with Stanford researcher Gary Steinberg.  And it could well be that the technique that they used will emerge as a critical tool in the effort to stave off the death of the $3 billion, stem cell program. The end could come as early as 2020 if agency supporters fail that year to win voter approval of $5 billion more for the program.

The medium in use by Loring and the agency is something called "Facebook Live."  It is a live streaming service that allows viewers to ask questions and comment during a webcast conducted by researchers or stem cell research advocates.  It is considerably more compelling than pre-recorded videos, says Forbes magazine, which reports that presentations on Facebook Live are viewed for three times as long as a static video. The thinking is that the interactive connection and the initial live presentation -- with its informality, spontaneity and lack of predictability --  are more interesting than your usual, pre-recorded sessions.

Facebook Live has been around since 2016.  but has rolled out slowly. According to a Google search this past weekend, only a handful of stem cell-connected enterprises have taken advantage of it. (See a few below.)

Viral Boost for the California Stem Cell Message

In its presentation last month, the stem cell agency started off with about 80 viewers. By the time of this writing the number of views of the video had skyrocketed to more than 6,800. Loring's presentation now stands at 1,600. Her number grew by 100 as this article was being written. That viral strength likely surpasses many static offerings in print coverage or conventional electronic news, which are largely onetime shots.

(The agency, on the morning following this posting, filed an item on its blog, hailing the success of the program. The item said, "We had an amazing response from people during the event and in the days since then with some 6,750 people watching the video and almost 1,000 people reacting by posting a comment or sharing it with friends. It was one of the most successful things we have ever done on Facebook so it’s not surprising that we plan on doing many more Facebook Live ‘Ask the Expert’ events in the future.")

One might ask: Why is the impact of this single Facebook event important in terms of a stem cell ballot campaign?

In recent years, the stem cell agency has slipped out of the public eye and is hard-pressed to attract widespread media attention, a situation that is commonplace for most state government departments. The agency's "value proposition" is not well understood, say officials at the agency, formally known as the California Institute for Regenerative Medicine (CIRM). 

To win approval of a proposed $5 billion bond measure in November 2020, however, CIRM will need strong support for its efforts, which have so far failed to deliver on the public's expectations that miraculous stem cell therapies are right around the corner. Those hopes were raised more than 13 years ago during the campaign that created the stem cell agency. Today its funds are running out. Cash for new awards is  expected to vanish by the end of next year.

Selling Hope to Half of California Families

Nonetheless, one of CIRM's notable products is hope -- not to mention 49 clinical trials that could lead to therapies for deadly diseases and widespread afflictions ranging from cancer to urinary incontinence.

In 2004, backers of the stem cell ballot measure declared that "medical problems that could benefit from stem cell research affect 128 million Americans including a child or adult in nearly half of all California families."

Reaching those California families is the key to unlocking their votes on behalf of the stem cell program. Facebook -- notably and coincidentally -- reaches nearly half of the Internet users  in California.

Using Facebook Live, or rival services, may well be the most effective way to connect with those important voters, especially with the help of the patient advocates who have been heavily involved with the agency. They bring the personal stories that resonate with voters and create an emotional appeal that is likely to trigger a favorable vote for more billions.

More services like Facebook Live will probably arise in the next 12 months. But Facebook has an advantage: the huge number of its users and an established Internet base that includes the patient advocate community and its organizations.

Writing on Forbes about business applications of Facebook Live, Steve Olenski said:
"Live video comes with a generous helping of transparency. Your influencer's voice will ring truer in a live conversation with fans than it does in a blog post. Viewers can engage with your product or service and the influencer in open conversation handled in real time.
"If you're looking for a compelling way to build trust with your audience, a live video is a great place to start."
Here are links to a few Facebook Live events involving stem cell-related matters: Difference between gene therapy and stem cell therapy, CAR T-Cell Therapy for Non-Hodgkin Lymphoma, Gene Therapy for Sickle Cell Disease.

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