How a see-through fish could one day lead to substitutes for bone marrow transplants

Human blood stem cells

For years researchers have struggled to create human blood stem cells in the lab. They have done it several times with animal models, but the human kind? Well, that’s proved a bit trickier. Now a CIRM-funded team at UC San Diego (UCSD) think they have cracked the code. And that would be great news for anyone who may ever need a bone marrow transplant.

Why are blood stem cells important? Well, they help create our red and white blood cells and platelets, critical elements in carrying oxygen to all our organs and fighting infections. They have also become one of the most important weapons we have to combat deadly diseases like leukemia and lymphoma. Unfortunately, today we depend on finding a perfect or near-perfect match to make bone marrow transplants as safe and effective as possible and without a perfect match many patients miss out. That’s why this news is so exciting.

Researchers at UCSD found that the process of creating new blood stem cells depends on the action of three molecules, not two as was previously thought.

Zebrafish

Here’s where it gets a bit complicated but stick with me. The team worked with zebrafish, which use the same method to create blood stem cells as people do but also have the advantage of being translucent, so you can watch what’s going on inside them as it happens.  They noticed that a molecule called Wnt9a touches down on a receptor called Fzd9b and brings along with it something called the epidermal growth factor receptor (EGFR). It’s the interaction of these three together that turns a stem cell into a blood cell.

In a news release, Stephanie Grainger, the first author of the study published in Nature Cell Biology, said this discovery could help lead to new ways to grow the cells in the lab.

“Previous attempts to develop blood stem cells in a laboratory dish have failed, and that may be in part because they didn’t take the interaction between EGFR and Wnt into account.”

If this new approach helps the team generate blood stem cells in the lab these could be used to create off-the-shelf blood stem cells, instead of bone marrow transplants, to treat people battling leukemia and/or lymphoma.

CIRM is also funding a number of other projects, several in clinical trials, that involve the use of blood stem cells. Those include treatments for: Beta Thalassemia; blood cancer; HIV/AIDS; and Severe Combined Immunodeficiency among others.

Advancing stem cell research in many ways

Speakers at the Alpha Stem Cell Clinics Network Symposium: Photo by Marco Sanchez

From Day One CIRM’s goal has been to advance stem cell research in California. We don’t do that just by funding the most promising research -though the 51 clinical trials we have funded to date clearly shows we do that rather well – but also by trying to bring the best minds in the field together to overcome problems.

Over the years we have held conferences, workshops and symposiums on everything from Parkinson’s disease, cerebral palsy and tissue engineering. Each one attracted the key players and stakeholders in the field, brainstorming ideas to get past obstacles and to explore new ways of developing therapies. It’s an attempt to get scientists, who would normally be rivals or competitors, to collaborate and partner together in finding the best way forward.

It’s not easy to do, and the results are not always obvious right away, but it is essential if we hope to live up to our mission of accelerating stem cell therapies to patients with unmet medical needs.

For example. This past week we helped organize two big events and were participants in another.

The first event we pulled together, in partnership with Cedars-Sinai Medical Center, was a workshop called “Brainstorm Neurodegeneration”. It brought together leaders in stem cell research, genomics, big data, patient advocacy and the Food and Drug Administration (FDA) to tackle some of the issues that have hampered progress in finding treatments for things like Parkinson’s, Alzheimer’s, ALS and Huntington’s disease.

We rather ambitiously subtitled the workshop “a cutting-edge meeting to disrupt the field” and while the two days of discussions didn’t resolve all the problems facing us it did produce some fascinating ideas and some tantalizing glimpses at ways to advance the field.

Alpha Stem Cell Clinics Network Symposium: Photo by Marco Sanchez

Two days later we partnered with UC San Francisco to host the Fourth Annual CIRM Alpha Stem Cell Clinics Network Symposium. This brought together the scientists who develop therapies, the doctors and nurses who deliver them, and the patients who are in need of them. The theme was “The Past, Present & Future of Regenerative Medicine” and included both a look at the initial discoveries in gene therapy that led us to where we are now as well as a look to the future when cellular therapies, we believe, will become a routine option for patients. 

Bringing these different groups together is important for us. We feel each has a key role to play in moving these projects and out of the lab and into clinical trials and that it is only by working together that they can succeed in producing the treatments and cures patients so desperately need.

Cierra Jackson: Photo by Marco Sanchez

As always it was the patients who surprised us. One, Cierra Danielle Jackson, talked about what it was like to be cured of her sickle cell disease. I think it’s fair to say that most in the audience expected Cierra to talk about her delight at no longer having the crippling and life-threatening condition. And she did. But she also talked about how hard it was adjusting to this new reality.

Cierra said sickle cell disease had been a part of her life for all her life, it shaped her daily life and her relationships with her family and many others. So, to suddenly have that no longer be a part of her caused a kind of identity crisis. Who was she now that she was no longer someone with sickle cell disease?

She talked about how people with most diseases were normal before they got sick, and will be normal after they are cured. But for people with sickle cell, being sick is all they have known. That was their normal. And now they have to adjust to a new normal.

It was a powerful reminder to everyone that in developing new treatments we have to consider the whole person, their psychological and emotional sides as well as the physical.

CIRM’s Dr. Maria Millan (right) at a panel presentation at the Stanford Drug Discovery Symposium. Panel from left to right are: James Doroshow, NCI; Sandy Weill, former CEO Citigroup; Allan Jones, CEO Allen Institute

And so on to the third event we were part of, the Stanford Drug Discovery Symposium. This was a high level, invitation-only scientific meeting that included some heavy hitters – such as Nobel Prize winners Paul Berg and  Randy Schekman, former FDA Commissioner Robert Califf. Over the course of two days they examined the role that philanthropy plays in advancing research, the increasingly important role of immunotherapy in battling diseases like cancer and how tools such as artificial intelligence and big data are shaping the future.

CIRM’s President and CEO, Dr. Maria Millan, was one of those invited to speak and she talked about how California’s investment in stem cell research is delivering Something Better than Hope – which by a happy coincidence is the title of our 2018 Annual Report. She highlighted some of the 51 clinical trials we have funded, and the lives that have been changed and saved by this research.

The presentations at these conferences and workshops are important, but so too are the conversations that happen outside the auditorium, over lunch or at coffee. Many great collaborations have happened when scientists get a chance to share ideas, or when researchers talk to patients about their ideas for a successful clinical trial.

It’s amazing what happens when you bring people together who might otherwise never have met. The ideas they come up with can change the world.

Mending Stem Cells: The Past, Present & Future of Regenerative Medicine

UCSF’s Mission Bay Campus

For years we have talked about the “promise” and the “potential” of stem cells to cure patients. But more and more we are seeing firsthand how stem cells can change a patient’s life, even saving it in some cases. That’s the theme of the 4th Annual CIRM Alpha Stem Cell Clinics Network Symposium.

It’s not your usual symposium because this brings together all the key players in the field – the scientists who do the research, the nurses and doctors who deliver the therapies, and the patients who get or need those therapies. And, of course, we’ll be there; because without CIRM’s funding to support that research and therapies none of this happens.

We are going to look at some of the exciting progress being made, and what is on the horizon. But along the way we’ll also tackle many of the questions that people pose to us every day. Questions such as:

  • How can you distinguish between a good clinical trial offering legitimate treatments vs a stem cell clinic offering sham treatments?
  • What about the Right to Try, can’t I just demand I get access to stem cell therapies?
  • How do I sign up for a clinical trial, and how much will it cost me?
  • What is the experience of patients that have participated in a stem cell clinical trial?

World class researchers will also talk about the real possibility of curing diseases like sickle cell disease on a national scale, which affect around 100,000 Americans, mostly African Americans and Hispanics. They’ll discuss the use of gene editing to battle hereditary diseases like Huntington’s. And they’ll highlight how they can engineer a patient’s own immune system cells to battle deadly cancers.

So, join us for what promises to be a fascinating day. It’s the cutting edge of science. And it’s all FREE.

Here’s where you can go to find out more information and to sign up for the event.

Stem cell byproducts provide insight into cure for spina bifida

A diagram of an infant born with spina bifida, a birth defect where there is an incomplete closing of the backbone portion of the spinal cord. Photo courtesy of the Texas Children’s Hospital website.

Some of you might remember a movie in the early 2000s by the name of “Miracle in Lane 2”. The film is based on an inspirational true story and revolves around a boy named Justin Yoder entering a soapbox derby competition. In the movie, Justin achieves success as a soapbox derby driver while adapting to the challenges of being in a wheelchair.

Scene from “Miracle in Lane 2”

The reason that Justin is unable to walk is due to a birth defect known as spina bifida, which causes an incomplete closing of the backbone portion of the spinal cord, exposing tissue and nerves. In addition to difficulties with walking, other problems associated with this condition are problems with bladder or bowel control and accumulation of fluid in the brain.

According to the Center for Disease Control (CDC) , each year about 1,645 babies in the US are born with spina bifida, with Hispanic women having the highest rate of children born with the condition. There is currently no cure for this condition, but researchers at UC Davis are one step closer to changing that.

Dr. Aijun Wang examining cells under a microscope. He has identified stem cell byproducts that protect neurons. Photo courtesy of UC Regents/UC Davis Health

Dr. Aijun Wang, Dr. Diana Farmer, and their research team have identified crucial byproducts produced by stem cells that play an important role in protecting neurons. These byproducts could assist with improving lower-limb motion in patients with spina bifida.

Prior to this discovery, Dr. Farmer and Dr. Wang demonstrated that prenatal surgery combined with connective tissue (e.g. stromal cells) derived from stem cells improved hind limb control in dogs with spina bifida. Below you can see a clip of two English bulldogs with spina bifida who are now able to walk.

Their findings were published in the Journal of the Federation of American Societies for Experimental Biology on February 12, 2019.

The team will use their findings to perfect the neuroprotective qualities of a stem cell treatment developed to improve locomotive problems associated with spina bifida.

In a public release posted by EurekaAlert!, Dr. Wang is quoted as saying, “We are excited about what we see so far and are anxious to further explore the clinical applications of this research.”

The discovery and development of a treatment for spina bifida was funded by a $5.66 million grant from CIRM. You can read more about that award and spina bifida on a previous blog post linked here.

Mending Stem Cells: The Past, Present and Future of Regenerative Medicine

To Mend: (verb used with object) to make (something broken, worn, torn or otherwise damaged) whole, sound or usable by repairing.

It’s remarkable to believe, but today doctors literally have the tools to repair damaged cells. These tools are being used to treat people with diseases that were once incurable. The field of regenerative medicine has made tremendous progress in the last 15 years, but how did these tools come about and what is the experience of patients being treated with them?

These questions, and hopefully yours too, are going to be answered at the fourth annual CIRM Alpha Stem Cell Clinics Symposium on April 18, 2019 at the University of California at San Francisco.

UCSF Mission Bay Campus

The symposium is free, and the program is designed with patients and the public in mind, so don’t be shy and put your scientific thinking caps on! A complete agenda may be found here

Perhaps one of the most remarkable discoveries in the past decade are new tools that enable doctors to “edit” or correct a patient’s own DNA. DNA correction tools came about because of a remarkable string of scientific breakthroughs. The symposium will dive into this history and discuss  how these tools are being used today to treat patients.

One specific example of the promise that DNA editing holds is for those with sickle cell disease (SCD), a condition where patients’ blood forming stem cells contain a genetic error that causes the disease. The symposium will describe how the CIRM Alpha Stem Cell Clinics Network, a series of medical centers across California whose focus is on stem cell clinical trials, are supporting work aimed at mending blood cells to cure debilitating diseases like SCD.

Doctors, nurses and patients involved with these trials will be telling their stories and describing their experiences. One important focus will be how Alpha Clinic teams are partnering with community members to ensure that patients, interested in new treatments, are informed about the availability of clinical trials and receive sufficient information to make the best treatment choices.

The fourth annual CIRM Alpha Stem Cell Clinics Symposium is an opportunity for patients, their families and the public to meet the pioneers who are literally mending a patients own stem cells to cure their disease.

For registration information go here.


Frustration, failure and finally hope in the search for treatments for spina bifida

diana farmer_2015

Dr. Diana Farmer and her team at UC. Davis

By any standards Dr. Diana Farmer is a determined woman who doesn’t let setbacks and failure deter her. As a fetal and neonatal surgeon, and the chair of the Department of Surgery at UC Davis Health, Dr. Farmer has spent years trying to develop a cure for spina bifida. She’s getting closer.

Dr. Farmer and her partner in this research, Dr. Aijun Wang, have already shown they can repair the damage spina bifida causes to the spinal cord, in the womb, in sheep and bulldogs. Last year the CIRM Board voted to fund her research to get the data needed to apply to the US Food and Drug Administration for permission to start a clinical trial in people.

That work is so promising that we decided to profile Dr. Farmer in our 2018 Annual Report.

Here’s excerpts from an interview we conducted with her as part of the Annual Report.

I have been working on this since 2008. We have been thinking about how to help kids with spina bifida walk. It’s not fatal disease but it is a miserable disease.

It’s horrible for parents who think they are about to have a healthy child suddenly be faced with a baby who faces a life long struggle with their health, everything from difficulty or inability to walk to bowel and bladder problems and life-threatening infections.

As a fetal surgeon we used to only focus on fatal diseases because otherwise kids would die. But as we made progress in the field, we had the opportunity to help others who didn’t have a fatal condition, in ways we couldn’t have done in the past.

I’ve always been fascinated by the placenta, it has lots of protective properties. So, we asked the question if we were able to sample fetal cells from the placenta, could we augment those cells, and use them to tissue engineer spinal injuries, in the womb, to improve the outcome for kids with spina bifida?

Dr. Aijun Wang and I have been working on this project for the last decade.  Ten years of work has taken us to this point where we are now ready to move this to the next level.

It’s amazing to me how long this process takes and that’s why we are so grateful to CIRM because this is a rare disease and finding funding for those is hard. A lot of people are scared about funding fetal surgery and CIRM has been a perfect partner in helping bring this approach, blending stem cell therapy and tissue engineering, together.

If this therapy is successful it will have a huge economic impact on California, and on the rest of the world. Because spina bifida is a lifelong condition involving many operations, many stays in the hospital, in some cases lifelong use of a wheelchair. This has a huge financial burden on the family. And because this doesn’t just affect the child but the whole family, it has a huge psychological burden on families. It affects them in so many ways; parents having to miss work or take time off work to care for their child, other children in the family feeling neglected because their brother or sister needs so much attention.

In the MOMS Trial (a study that looked at prenatal – before birth – and postnatal – after birth – surgery to repair a defect in the spinal cord and showed that prenatal surgery had strong, long-term benefits and some risks) we showed that we could operate on the fetus before birth and help them. The fact that there was any improvement – doubling the number of kids who could walk from 20 to 40% showed this spinal cord injury is not a permanent situation and also showed there was some plasticity in the spinal cord, some potential for improvement. And so, the next question was can we do more. And that’s why we are trying this.

It’s pretty amazing. We are pretty excited.

The thing that makes surgeon-scientists feel so passionate is that we don’t just ask the fundamental questions, we ask questions in order to cure a problem in patients. I grew up in an environment where people were always asking “how can we do it better, how can we improve?”

There were many times of frustration, many times when cell types we explored and worked with didn’t work. But it’s the patients, seeing them, that keeps me motivated to do the science, to keep persevering. That’s the beauty of being a clinician-scientist. We can ask questions in a different way and look at data in a different way because we are driven by patient outcomes. So, whenever we get stuck in the rabbit hole of theoretical problems, we look to the patients for inspiration to keep going.

I am very cognizant of stirring up false hope, knowing that what occurs in animal models doesn’t always translate into humans. But we are optimistic, and I am anxious to get going.

 

71 for Proposition 71

Proposition 71 is the state ballot initiative that created California’s Stem Cell Agency. This month, the Agency reached another milestone when the 71st clinical trial was initiated in the CIRM Alpha Stem Cell Clinics (ASCC) Network. The ASCC Network deploys specialized teams of doctors, nurses and laboratory technicians to conduct stem cell clinical trials at leading California Medical Centers.

StateClinics_Image_CMYK

These teams work with academic and industry partners to support patient-centered for over 40 distinct diseases including:

  • Amyotrophic Lateral Sclerosis (ALS)
  • Brain Injury & Stroke
  • Cancer at Multiple Sites
  • Diabetes Type 1
  • Eye Disease / Blindness Heart Failure
  • HIV / AIDS
  • Kidney Failure
  • Severe Combined Immunodeficiency (SCID)
  • Sickle Cell Anemia
  • Spinal Cord Injury

These clinical trials have treated over 400 patients and counting. The Alpha Stem Cell Clinics are part of CIRM’s Strategic Infrastructure. The Strategic Infrastructure program which was developed to support the growth of stem cell / regenerative medicine in California. A comprehensive update of CIRM’s Infrastructure Program was provided to our Board, the ICOC.

CIRM’s infrastructure catalyzes stem cell / regenerative medicine by providing resources to all qualified researchers and organizations requiring specialized expertise. For example, the Alpha Clinics Network is supporting clinical trials from around the world.

Many of these trials are sponsored by commercial companies that have no CIRM funding. To date, the ASCC Network has over $27 million in contracts with outside sponsors. These contracts serve to leverage CIRMs investment and provide the Network’s medical centers with a diverse portfolio of clinical trials to address patients’’ unmet medical needs.

Alpha Clinics – Key Performance Metrics

  • 70+ Clinical Trials
  • 400+ Patients Treated
  • 40+ Disease Indications
  • Over $27 million in contracts with commercial sponsors

The CIRM Alpha Stem Cell Clinics and broader Infrastructure Programs are supporting stem cell research and regenerative medicine at every level, from laboratory research to product manufacturing to delivery to patients. This infrastructure has emerged to make California the world leader in regenerative medicine. It all started because California’s residents supported a ballot measure and today we have 71 clinical trials for 71.

 

 

Promising Approach to Curing Spina Bifida Gets $5.6 Million from Stem Cell Agency

300px-Spina-bifida

Every day in the U.S. four children are born with spina bifida. It is the most common cause of lifelong paralysis and also frequently leads to other serious health problems affecting the bowel and bladder. The impact on families is enormous. A new approach to repairing the defect that causes spina bifida was today awarded $5.66 million by the Board of the California Institute for Regenerative Medicine (CIRM).

In spina bifida the spinal cord doesn’t form properly, in many cases leaving a section of it open, exposing tissues and nerves. The current standard of care is surgery, but even this leaves almost 60% of children unable to walk independently. Diana Farmer MD, and Aijun Wang PhD at U.C. Davis will use mesenchymal stem cells, taken from a donor placenta, and place them on a form of synthetic scaffold over the injury site in the womb. Tests in animals show this approach was able to repair the defect and prevent paralysis.

“Spina bifida is a devastating condition for babies born with this disorder and the families who care for them,” says Maria T. Millan, MD, President & CEO of CIRM. “CIRM has funded this important work from its earliest stages and we are committed to working with Dr. Farmer’s team to moving this work to the stage where it can be tested in patients.”

The CLIN1 award will provide funding to enable the UC Davis team to do the final testing and preparations needed to apply to the FDA for permission to start a clinical trial.

Dr. Farmer says she and Dr. Wang, have been working on this approach for more than ten years and are excited about being able to take the next step.

“There were many times of frustration, many times when cell types we explored and worked with didn’t work,” says Dr. Farmer. “But it’s the patients, seeing them, talking to them and working with them, that keeps me motivated to do the science, to keep persevering.”

If this therapy is successful it will have a huge economic impact on California, and on the rest of the world. Because spina bifida is a lifelong condition involving many operations, many stays in the hospital and, in some cases, lifelong use of a wheelchair this has a huge financial, and psychological, burden on the family.

“It affects them in so many ways; parents having to miss work or take time off work to care for their child, other children in the family feeling neglected because their brother or sister needs so much attention,” says Dr. Farmer. “That’s why we are so grateful to CIRM. Because this is a rare disease and finding funding for those is hard. CIRM has been a perfect partner in helping bring this approach, blending stem cell therapy and tissue engineering, together to help these families.”

This video shows English bulldogs treated with this approach who are now able to walk:

Hits and Myths as people celebrate Stem Cell Awareness Day

UC Davis #1

Stem Cell Awareness Day at UC Davis

Every year, the second Wednesday in October is set aside as Stem Cell Awareness Day, a time to celebrate the progress being made in the field and to remind us of the challenges that lie ahead.

While the event began here in California in 2008, with then-Governor Arnold Schwarzenegger highlighting the work of CIRM, saying: ”The discoveries being made today in our Golden State will have a great impact on many around the world for generations to come.” It has since grown to become a global event.

Here in California, for example, UC Davis and the University of Southern California (USC) both held events to mark the day.

At UC Davis Jan Nolta, PhD., the Director of the Stem Cell Program, introduced a series of speakers who highlighted the terrific work being done at the university. Peter Belafsky talked about using stem cells to repair damaged trachea and to help people who are experiencing voice or swallowing disorders. Mark Lee highlighted the progress being made in using stem cells to repair hard-to-heal broken bones. Aijun Wang focused on some really exciting work that could one day lead to a therapy for spina bifida (including some ridiculously cute video of English bulldogs who are able to walk again because of this therapy.)

USC hosted 100 local high school students for a panel presentation and discussion about careers in stem cell research. The panel featured four scientists talking about their experience, why the students should think about a career in science and how to go about planning one. USC put together a terrific video of the researchers talking about their experiences, something that can help any student around the US consider becoming part of the future of stem cell research.

Similar events were held in other institutions around California. But the celebration wasn’t limited to the Golden State. At the Texas Heart Institute in Houston, Texas, they held an event to talk to the public about the clinical trials they are supporting using stem cells to help people suffering from heart failure or other heart-related issues.

RegMedNet

Finally, the UK-based RegMedNet, a community site that unites the diverse regenerative medicine community, marked the day by exploring some of the myths and misconceptions still surrounding stem cells and stem cell research.

You can read those here.

Every group takes a different approach to celebrating Stem Cell Awareness Day, but each is united by a common desire, to help people understand the progress being made in finding new treatments and even cures for people with unmet medical needs.

A brief history of the Stem Cell Agency

On Wednesday, August 15 the California State Assembly Select Committee on Biotechnology held an informational hearing on CIRM as part of its mission of ensuring the legislature is up to date and informed about the biotech industry in California. The committee heard from CIRM’s President and CEO Dr. Maria T. Millan and the Vice Chair of our Board, Senator Art Torres (Ret.); two of CIRM’s Patient Advocates (Pawash Priyank and Don Reed) and Dr. Jan Nolta, the Director of the Institute for Regenerative Cures at UC Davis.

The final speaker was David Jensen, whose California Stem Cell Report blog has charted the history of CIRM since its inception. At CIRM we know that not everyone agrees with us all the time, or supports all the decisions we have made in the years since we were approved by voters in 2004, but we do pride ourselves on being open to a thoughtful, vigorous debate on all aspects of stem cell research. David’s presentation to the committee was nothing if not thoughtful, and we thought you might enjoy reading it and so we are presenting it here in its entirety.

For those who prefer to watch than read, here is a video of the entire hearing:

https://www.assembly.ca.gov/media/assembly-select-committee-biotechnology-20180815/video

California’s Stem Cell “Gold Rush:” A Brief Overview of the State’s $3 Billion Stem Cell Agency
Prepared testimony by David Jensen, publisher/editor of the California Stem Cell Report, before the Assembly Select Committee on Biotechnology, Aug. 15, 2018
I was in Mazatlan in Mexico in the fall of 2004 when I first heard about the creation of
California’s stem cell agency. I was reading the Wall Street Journal online and saw a headline that said a new Gold Rush was about to begin in California — this one involving stem cells instead of nuggets.

“Holy Argonauts,” I said to myself, using the term, of course, that refers to the tens of thousands of people who rushed to the California gold fields in 1849. I wanted to know more about what was likely to happen with this new stem cell gold rush.

Today, nearly 14 years later, I still want to know more about the California Institute for
Regenerative Medicine or CIRM, as the agency is formally known. But I can tell you that certain facts are clear.

Borrowing and Autonomy
The agency is unique in California history and among the states throughout the nation. It is the first state agency to fund scientific research with billions of dollars – all of it borrowed. At one point in its history, it is safe to say that the agency was the largest single source of funding in the world for human embryonic stem cell research.

The agency operates with financial and oversight autonomy that is rare in California government, courtesy of the ballot initiative that created it. But that measure also proved to be both a blessing and a curse. The agency’s financial autonomy has allowed it to provide a reasonably steady stream of cash over a number of years, something that is necessary to sustain the long-term research that is critical for development of widely available treatments.

At the same time, the ballot measure carried the agency’s death warrant — no more money after the $3 billion was gone. Cash for new awards is now expected to run out at the end of next year. Over its life, the agency has had a national and somewhat more modestly global impact, both as a source of funding and international cooperation, but also in staying the course on human embryonic stem cell research when the federal government was backing away from it.

Beyond that, the stem cell agency is the only state department whose primary objective is to produce a marketable commercial product. In this case, a cure or treatment for afflictions now nearly untreatable.

Finally, I am all but certain that CIRM is the only state agency that takes back money when a project winds up on the rocks. By the end of last month, that figure totalled in recent years more than $34 million in two big categories of awards. This sort of cash recovery is not a practice that occurs with federal research dollars. With CIRM the money goes back into the pot for more research aimed at treating horrible afflictions.

Evaluations of the Research Effort
Nonetheless the agency has hit some shoals from time to time. In 2010, the agency’s governing board commissioned a $700,000 study of its efforts by the prestigious Institute of Medicine. Two years later, the IOM reported to CIRM that it had some significant flaws.

The IOM study said that the agency had “achieved many notable results.” But it also
recommended sweeping changes to remove conflict of interest problems, clean up a troubling dual-executive arrangement and fundamentally change the nature of the governing board.

The report said,“Far too many board members represent organizations that receive CIRM funding or benefit from that funding. These competing personal and professional interests compromise the perceived independence of the ICOC (the CIRM governing board), introduce potential bias into the board’s decision making, and threaten to undermine confidence in the board.”

The conflict issues are built in by the ballot measure, which gave potential recipient institutions seats on the 29-member governing board. Indeed, in 2017, the last time I calculated the correlation between the board and awards, roughly 90 percent of the money given out by CIRM had gone to institutions with ties to members of the governing board.

About two months after the IOM presented its report, the CIRM board approved a new policy that bars 13 of its 29 members from voting on any grants whatsoever to help deal with questions concerning conflicts of interest on the board.

Other studies about the agency’s performance resulted from a 2010 law in which the legislature modified the initiative to require triennial performance audits that would be paid for by the agency itself. The requirement specifically excluded “scientific performance” from the audit.

The first audit results came in 2012 and contained 27 recommendations for improvement. The most recent performance audit came last spring. The audit firm, Moss Adams, recommended improvements in the areas of private fund-raising, retention of staff and better utilization of board members. The board was told that the agency had made “incredible progress” and that the auditors “usually see a lot of good things.”

The Story of CIRM 2.0
In recent years the agency has been on a self-improvement regime. The effort began in 2014 and was dubbed CIRM 2.0 — a term that was originally coined by a stem cell researcher at UC Davis.

The new direction and emphasis was described by the agency as “radical.” It was aimed at improving speed, efficiency and innovation. And it seems to have largely succeeded.
In 2014, it took almost two years for a good idea to go from application to the final funding stage. The goal was to shorten that to 120 days. Delays in funding are of particular concern to businesses, often for cash flow reasons, but they also mean delays in actually developing a treatment.

This week, the agency said the cash delivery figure now stands at less than 90 days for clinical awards and about 120 days for translational awards.

In 2014, the agency was participating in nine clinical trials, the last stage before a treatment is certified by the federal government for widespread use. Today the agency is involved in 49. In 2014, about 50 patients were involved in those trials. Today the figure is more than 800.

One of the more interesting aspects of CIRM 2.0 marked a departure from what might be called an academic pass-fail approach to the “final exam” for applications from scientists. Instead, CIRM is engaged in a more partner-oriented approach that can be found in some businesses.

Instead of flatly failing an application that is not quite ready for prime time, the idea is to coach applicants along to help bring them up to approval level. Today the agency can count 30 applications that won approval through that process. All of which is work could have slipped away in the more distant past.

CIRM and the Biotech Biz
CIRM is now much more engaged with industry than during its earlier years, when it drew bitter criticism from some business executives. Engagement with biotech firms is critical to bringing a treatment to the public. CIRM is not in the business of actually manufacturing, marketing and selling products. That is a matter left to the private sector.

One reason for closer business connections involves maturation of the work in the field, which has brought research closer to reality. But it is also due to a different focus within the agency as top management has changed.

One of the more difficult areas involving stem cell research and likely treatments is their cost. It is rare to hear researchers or companies talk forthrightly in public about specific dollar amounts. But the cost of drugs and treatment are high visibility matters for patients and elected officials. And estimates of stem cell treatments have run up to at least $900,000.

In 2010, the California legislature moved to help assure affordability by requiring grantees to submit affordable access plans with the caveat that the agency could waive that requirement. How that will ultimately play out as actual products come into the marketplace is yet to be determined.

The Public Policy Questions
A number of significant public policy questions surround the California’s stem cell program involving its creation and execution. They include:
● Is a ballot initiative the best way to approach research and create new state programs?
The initiative is very difficult to alter when changes are needed or priorities change. .
● Does the state have higher health priorities, such as prenatal health care, than supplying
researchers with cash that they could well secure from other sources?
● Is borrowing money to finance the research the best way to go about it? The interest
expense raise the total cost of a $20 million research award to $40 million.
● Should executives of potential recipient institutions serve on the board that awards their employers hundreds of millions of dollars?

This is just a short list of some of the policy matters. Other questions can and should be asked in the wake of the agency’s nearly 14 years of work.

Lives Saved but No Widespread Therapies
Returning to our earlier list of the clear facts about CIRM, another fact is that lives have been saved as the result of clinical trials that the agency it has helped to finance. The youngster from Folsom mentioned earlier in this hearing is one of a number of cases.

That said, these patients received treatment in clinical trials, which may or may not succeed in producing a commercial product that is available to the general public.

Little doubt exists that the agency has advanced the stem cell field and is building towards a critical mass in California. The burgeoning research program at UC Davis, with $138 million in CIRM funding, is one example. Another is the $50 million Alpha Clinic network aimed at creating powerful collaboration within institutions and throughout the state. In addition to Davis, UC San Francisco, UCLA, UC Irvine, UC San Diego and the City of Hope in the Los Angeles area are all part of the Alpha network.

Nonetheless, CIRM has not yet backed a stem cell treatment that is ready for widespread use and fulfilled the voter expectations from 2004 that stem cell cures were right around the corner.

The agency itself also has something of a deadline that is right around the corner in political and scientific terms. Backers of the agency are hoping for another ballot initiative in November 2020 that would pump $5 billion into the program and stave off its slow demise as research winds down. Development of a stem cell treatment that would resonate with voters would be an invaluable development to encourage voters to continue this unique experiment — even if California’s stem cell gold rush does not quite measure up to the dramatic events of 169 years ago.
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