A word from our Chair, several in fact

In 2005, the New Oxford American Dictionary named “podcast” its word of the year. At the time a podcast was something many had heard of but not that many actually tuned in to. My how times have changed. Now there are some two million podcasts to chose from, at least according to the New York Times, and who am I to question them.

Yesterday, in the same New York Times, TV writer Margaret Lyons, wrote about how the pandemic helped turn her from TV to podcasts: “Much in the way I grew to prefer an old-fashioned phone call to a video chat, podcasts, not television, became my go-to medium in quarantine. With their shorter lead times and intimate production values, they felt more immediate and more relevant than ever before.”

I mention this because an old colleague of ours at CIRM, Neil Littman, has just launched his own podcast and the first guest on it was Jonathan Thomas, Chair of the CIRM Board. Their conversation ranged from CIRM’s past to the future of the regenerative field as a whole, with a few interesting diversions along the way. It’s fun listening. And as Margaret Lyons said it might be more immediate and more relevant than ever before.

Charting a course for the future

A new home for stem cell research?

Have you ever been at a party where someone says “hey, I’ve got a good idea” and then before you know it everyone in the room is adding to it with ideas and suggestions of their own and suddenly you find yourself with 27 pages of notes, all of them really great ideas. No, me neither. At least, not until yesterday when we held the first meeting of our Scientific Strategy Advisory Panel.

This is a group that was set up as part of Proposition 14, the ballot initiative that refunded CIRM last November (thanks again everyone who voted for that). The idea was to create a panel of world class scientists and regulatory experts to help guide and advise our Board on how to advance our mission. It’s a pretty impressive group too. You can see who is on the SSAP here.  

The meeting involved some CIRM grantees talking a little about their work but mostly highlighting problems or obstacles they considered key issues for the future of the field as a whole. And that’s where the ideas and suggestions really started flowing hard and fast.

It started out innocently enough with Dr. Amander Clark of UCLA talking about some of the needs for Discovery or basic research. She advocated for a consortium approach (this quickly became a theme for many other experts) with researchers collaborating and sharing data and findings to help move the field along.

She also called for greater diversity in research, including collecting diverse cell samples at the basic research level, so that if a program advanced to later stages the findings would be relevant to a wide cross section of society rather than just a narrow group.

Dr. Clark also said that as well as supporting research into neurodegenerative diseases, such as Alzheimer’s and Parkinson’s, there needed to be a greater emphasis on neurological conditions such as autism, bipolar disorder and other mental health problems.

(CIRM is already committed to both increasing diversity at all levels of research and expanding mental health research so this was welcome confirmation we are on the right track).

Dr. Mike McCun called for CIRM to take a leadership role in funding fetal tissue research, things the federal government can’t or won’t support, saying this could really help in developing an understanding of prenatal diseases.

Dr. Christine Mummery, President of ISSCR, advocated for support for early embryo research to deepen our understanding of early human development and also help with issues of infertility.

Then the ideas started coming really fast:

  • There’s a need for knowledge networks to share information in real-time not months later after results are published.
  • We need standardization across the field to make it easier to compare study results.
  • We need automation to reduce inconsistency in things like feeding and growing cells, manufacturing cells etc.
  • Equitable access to CRISPR gene-editing treatments, particularly for underserved communities and for rare diseases where big pharmaceutical companies are less likely to invest the money needed to develop a treatment.
  • Do a better job of developing combination therapies – involving stem cells and more traditional medications.

One idea that seemed to generate a lot of enthusiasm – perhaps as much due to the name that Patrik Brundin of the Van Andel Institute gave it – was the creation of a CIRM Hotel California, a place where researchers could go to learn new techniques, to share ideas, to collaborate and maybe take a nice cold drink by the pool (OK, I just made that last bit up to see if you were paying attention).

The meeting was remarkable not just for the flood of ideas, but also for its sense of collegiality.  Peter Marks, the director of the Food and Drug Administration’s Center for Biologics Evaluation and Research (FDA-CBER) captured that sense perfectly when he said the point of everyone working together, collaborating, sharing information and data, is to get these projects over the finish line. The more we work together, the more we will succeed.

U.C. San Diego Scientist Larry Goldstein Joins Stem Cell Agency’s Board

Larry Goldstein, PhD.

Larry Goldstein PhD, has many titles, one of which sums up his career perfectly, “Distinguished Professor”. Dr. Goldstein has distinguished himself on many fronts, making him an ideal addition to the governing Board of the California Institute for Regenerative Medicine (CIRM).

Dr. Goldstein – everyone calls him Larry – is a Cell Biologist, Geneticist and Neuroscientist. He worked with many colleagues to launch the UC San Diego Stem Cell program, the Sanford Consortium for Regenerative Medicine and the Sanford Stem Cell Clinical Center. He has received the Public Service Award from the American Society for Cell Biology and has had a Public Policy Fellowship named for him by the International Society for Stem Cell Research. He is a member of the American Academy of Arts and Sciences and last year was named a member of the prestigious National Academy of Sciences.

“I look forward to working with the ICOC and CIRM staff to ensure that the best and most promising stem cell research and medicine is fostered and funded,” Larry said.

For more than 25 years Larry’s work has targeted the brain and, in particular, Alzheimer’s disease and amyotrophic lateral sclerosis (ALS) better known as Lou Gehrig’s disease.

In 2012 his team was the first to create stem cell models for two different forms of Alzheimer’s, the hereditary and the sporadic forms. This gave researchers a new way of studying the disease, helping them better understand what causes it and looking at new ways of treating it.

He was appointed to the CIRM Board by Pradeep Khosla, the Chancellor of U.C. San Diego saying he is “gratified you are assuming this important role.”

Jonathan Thomas, JD, PhD., Chair of the CIRM Board, welcome the appointment saying “I have known Larry for many years and have nothing but the highest regard for him as a scientist, a leader, and a great champion of stem cell research. He is also an innovative thinker and that will be invaluable to us as we move into a second chapter in the life of CIRM.”

Larry was born in Buffalo, New York and grew up in Thousand Oaks, California. He graduated from UC San Diego with a degree in Biology in 1976 and from the University of Washington with a Ph. D. in Genetics in 1980. He joined the faculty in Cell and Developmental Biology at Harvard University in 1984 where he was promoted to Full Professor with tenure in 1990. He returned to UC San Diego and the Howard Hughes Medical Institute in 1993. After 45 years pursuing cutting edge lab-based research Larry is now transitioning to an administrative and executive role at UC San Diego where he will serve as the Senior Advisor for Stem Cell Research and Policy to the Vice Chancellor of Health Sciences.

He replaces David Brenner who is standing down after completing two terms on the Board.

UCSF Nursing Professor Joins CIRM Board

Elena Flowers, PhD, RN, newest member of the CIRM Board: Photo courtesy UCSF

Elena Flowers, PhD, RN, an associate professor of physiological nursing at the University of California, San Francisco (UCSF) is joining the Board of the California Institute for Regenerative Medicine (CIRM), the state’s Stem Cell Agency.

Dr. Flowers was appointed to the Board by State Controller Betty T. Yee who said: “Ms. Flowers’ experience and express commitment to equitable health outcomes for California’s diverse communities will bring a valued perspective to the work ahead.”

Dr. Flowers is a member of the UCSF Institute for Human Genetics and the International Society of Nurses in Genetics. As a researcher her work focuses on genomics involving precision medicine and risk factors for cardiovascular health and type 2 diabetes. She is also a teacher and has lectured internationally on issues such as topics from racial disparities in Type 2 Diabetes to the implications of genomic technologies for the nursing workforce.

CIRM Board Chair, Jonathan Thomas, PhD, JD, welcomed the appointment: “Dr. Flowers brings a wealth of experience and expertise to our Board and, as a nurse, she will bring a different perspective to the work we do and help us in trying to better address the needs of underserved communities.” 

“I am honored to have the opportunity to serve the citizens of California in this capacity,” says Dr. Flowers. “CIRM has ambitious goals, seeking to improve upon common limitations of public research agencies by its commitment to delivering meaningful findings and ultimately treatments for patients as rapidly as possible. I’m particularly committed to improving inclusion and access to these treatments across the entire diverse California population.”

Dr. Flowers got her undergraduate degree at UC Davis and then served as a research assistant at Zuckerberg San Francisco General Hospital. She then went on to get her MS and Doctor of Philosophy degrees at the UCSF School of Nursing.

In her spare time she has no spare time because she is the mother of two young daughters.

Surviving with Joy

Dr. Tippi MacKenzie (left) of UCSF Benioff Children’s Hospital San Francisco, visits with newborn Elianna and parents Nichelle Obar and Chris Constantino. Photo by Noah Berger

Alpha thalassemia major is, by any stretch of the imagination, a dreadful, heart breaker of a disease. It’s caused by four missing or mutated genes and it almost always leads to a fetus dying before delivery or shortly after birth. Treatments are limited and in the past many parents were told that all they can do is prepare for the worst.

Now, however, there is new hope with new approaches, including one supported by CIRM, helping keep these children alive and giving them a chance at a normal life.

Thalassemias are a group of blood disorders that affect the way the body makes hemoglobin, which helps in carrying oxygen throughout the body. In alpha thalassemia major it’s the lack of alpha globin, a key part of hemoglobin, that causes the problem. Current treatment requires in blood transfusions to the fetus while it is still in the womb, and monthly blood transfusions for life after delivery, or a bone marrow transplant if a suitable donor is identified.

A clinical trial run by University of California San Francisco’s Dr. Tippi MacKenzie – funded by CIRM – is using a slightly different approach. The team takes stem cells from the mother’s bone marrow and then infuses them into the fetus. If accepted by the baby’s bone marrow, these stem cells can then mature into healthy blood cells. The hope is that one day this method will enable children to be born with a healthy blood supply and not need regular transfusions.

Treating these babies, saving their lives, is the focus of a short film from UCSF called “Surviving with Joy”. It’s a testament to the power of medicine, and the courage and resilience of parents who never stopped looking for a way to help their child.

Tissues are optional but advised.

Month of CIRM: Making sure stem cell therapies don’t get lost in Translation

All this month we are using our blog and social media to highlight a new chapter in CIRM’s life, thanks to the voters approving Proposition 14. We are looking back at what we have done since we were created in 2004, and also looking forward to the future. Today we feature a blog written by two of our fabulous Discovery and Translation team Science Officers, Dr. Kent Fitzgerald and Dr. Ross Okamura.

Dr. Ross Okamura

If you believe that you can know a person by their deeds, the partnership opportunities offered by CIRM illustrate what we, as an agency, believe is the most effective way to deliver on our mission statement, accelerating regenerative medicine treatments to patients with unmet medical needs.

Dr. Kent Fitzgerald

 In our past, we have offered awards covering basic biology projects which in turn provided the foundation to produce promising therapies  to ease human suffering.  But those are only the first steps in an elaborate process.

In order to bring these potential therapies to the clinic, selected drug candidates must next go through a set of activities designed to prepare them for review by the Food and Drug Administration (FDA). For cell therapies, the first formal review is often the Pre- Investigational New Drug Application Consultation or pre-IND.  This stage of drug development is commonly referred to as Translational, bridging the gap between our Discovery or early stage research and Clinical Trial programs.

One of our goals at CIRM is to prepare Translational projects we fund for that  pre-IND meeting with the FDA, to help them gather data that support the hope this approach will be both safe and effective in patients.  Holding this meeting with the FDA is the first step in the often lengthy process of conducting FDA regulated clinical trials and hopefully bringing an approved therapy to patients.

What type of work is required for a promising candidate to move from the Discovery stage into FDA regulated development?  To address the needs of Translational science, CIRM offers the Translational Research Project funding opportunity.  Activities that CIRM supports at the Translational stage include:

  • Process Development to allow manufacturing of the candidate therapy under Good Manufacturing Practices (GMP). This is to show that they can manufacture  at a large enough scale to treat patients.
  • Assay development and qualification of measurements to determine whether the drug is being manufactured safely while retaining its curative properties.
  • Studies to determine the optimal dose and the best way to deliver that dose.
  • Pilot safety studies looking how the patient might respond after treatment with the drug.
  • The development of a clinical plan indicating under what rules and conditions the drug might be prescribed to a patient. 

These, and other activities supported under our Translational funding program, all help to inform the FDA when they consider what pivotal studies they will require prior to approving an Investigational New Drug (IND) application, the next step in the regulatory approval process.

Since CIRM first offered programs specifically aimed at addressing the Translational stage of therapeutic candidates we have made 41 awards totaling approximately $150 million in funding.  To date, 13 have successfully completed and achieved their program goals, while 19 others are still actively working towards meeting their objective.  Additionally, three (treating Spina Bifida, Osteonecrosis, and Sickle Cell Disease) of the 13 programs have gone on to receive further CIRM support through our Clinical Stage programs.

During our time administering these awards, CIRM has actively partnered with our grantees to navigate what is required to bring a therapy from the bench to the bedside.  CIRM operationalizes this by setting milestones that provide clear definitions of success, specific goals the researchers have to meet to advance the project and also by providing resources for a dedicated project manager to help ensure the project can keep the big picture in mind while executing on their scientific progress. 

Throughout all this we partner with the researchers to support them in every possible way. For example, CIRM provides the project teams with Translational Advisory Panels (TAPs, modeled after the CIRM’s Clinical Advisory Panels) which bring in outside subject matter experts as well as patient advocates to help provide additional scientific, regulatory and clinical expertise to guide the development of the program at no additional cost to the grantees.  One of the enduring benefits that we hope to provide to researchers and organizations is a practical mastery of translational drug development so that they may continue to advance new and exciting therapies to all patients.

Through CIRM’s strong and continued support of this difficult stage of development, CIRM has developed an internal practical expertise in advancing projects through Translation.  We employ our experience to guide our awardees so they can avoid common pitfalls in the development of cell and gene therapies. The end goal is simple, helping to accelerate their path to the clinic and fulfilling the mission of CIRM that has been twice given to us by the voters of California, bringing treatments to patients suffering from unmet medical needs.

Month of CIRM: Battling COVID-19

All this month we are using our blog and social media to highlight a new chapter in CIRM’s life, thanks to the people of California approving Proposition 14. We are looking back at what we have done since we were created in 2004, and also looking forward to the future.

Dr. John Zaia, City of Hope stem cell researcher

The news that effective vaccines have been developed to help fight COVID-19 was a truly bright spot at the end of a very dark year. But it will be months, in some countries years, before we have enough vaccines to protect everyone. That’s why it’s so important to keep pushing for more effective ways to help people who get infected with the virus.

One of those ways is in a clinical study that CIRM is funding with City of Hope’s Dr. John Zaia. Dr. Zaia and his team, in partnership with the Translational Genomics Research Institute (TGen) in Flagstaff, Arizona, are using something called convalescent plasma to try and help people who have contracted the virus. Here’s the website they have created for the study.

Plasma is a part of our blood that carries proteins, called antibodies, that help defend our bodies against viral infections. When a patient recovers from COVID-19, their blood plasma contains antibodies against the virus. The hope is that those antibodies can now be used as a potential treatment for COVID-19 to help people who are newly infected. 

To carry out the study they are using clinical trial sites around California, including some of the CIRM Alpha Stem Cell Network clinics.

For the study to succeed they’ll first need people who have recovered from the virus to donate blood. That’s particularly appropriate in January because this is National Volunteer Blood Donor Month.

The team has three elements to their approach:

  • A rapid-response screening program to screen potential COVID-19 convalescent plasma donors, particularly in underserved communities.
  • A laboratory center that can analyze the anti-SARS-CoV-2 antibodies properties in COVID-19 convalescent plasma.
  • An analysis of the clinical course of the disease in COVID-19 patients to identify whether antibody properties correlate with clinical benefit of COVID-19 convalescent plasma.

There’s reason to believe this approach might work. A study published this week in the New England Journal of Medicine, found that blood plasma from people who have recovered from COVID-19 can help older adults and prevent them from getting seriously ill with the virus if they get the plasma within a few days of becoming infected.

We are used to thinking of blood donations as being used to help people after surgery or who have been in an accident. In this study the donations serve another purpose, but one that is no less important. The World Health Organization describes blood as “the most precious gift that anyone can give to another person — the gift of life. A decision to donate your blood can save a life, or even several if your blood is separated into its components — red cells, platelets and plasma.”

That plasma could help in developing more effective treatments against the virus. Because until we have enough vaccines for everyone, we are still going to need as much help as we can get in fighting COVID-19. The recent surge in cases throughout the US and Europe are a reminder that this virus is far from under control. We have already lost far too many people. So, if you have recently recovered from the virus, or know someone who has, consider donating blood to this study. It could prove to be a lifesaver.

For more information about the study and how you can be part of it, click here.

Month of CIRM: Reviewing Review

Dr. Gil Sambrano, Vice President Portfolio & Review

All this month we are using our blog and social media to highlight a new chapter in CIRM’s life, thanks to the voters approving Proposition 14. We are looking back at what we have done since we were created in 2004, and also looking forward to the future. Today we take a look at our Review team.

Many people who have to drive every day don’t really think about what’s going on under the hood of their car. As long as the engine works and gets them from A to B, they’re happy. I think the same is true about CIRM’s Review team. Many people don’t really think about all the moving parts that go into reviewing a promising new stem cell therapy.

But that’s a shame, because they are really missing out on watching a truly impressive engine at work.

Just consider the simple fact that since CIRM started about 4,000 companies, groups and individuals have applied to us for funding. Just take a moment to consider that number. Four thousand. Then consider that at no time have there been more than 5 people working in the review team. That’s right. Just 5 people. And more recently there have been substantially fewer. That’s a lot of projects and not a lot of people to review them. So how do they do it? Easy. They’re brilliant.

First, as applications come in they are scrutinized to make sure they meet specific eligibility requirements; do they involve stem cells, is the application complete, is it the right stage of research, is the budget they are proposing appropriate for the work they want to do etc. If they pass that initial appraisal, they then move on to the second round, the Grants Working Group or GWG.

The GWG consists of independent scientific experts from all over the US, all over the world in fact. However, none are from California because we want to ensure there are no possible conflicts of interest. When I say experts, I do mean experts. These are among the top in their field and are highly sought after to do reviews with the National Institutes of Health etc.

Mark Noble, PhD, the Director of the Stem Cell and Regenerative Medicine Institute at the University of Rochester, is a long-time member of the GWG. He says it’s a unique group of people:

“It’s a wonderful scientific education because you come to these meetings and someone is putting in a grant on diabetes and someone’s putting in a  grant on repairing the damage to the heart or spinal cord injury or they have a device that will allow you to transplant cells better and there are people  in the room that are able to talk knowledgeably about each of these areas and understand how this plays into medicine and how it might work in terms of actual financial development and how it might work in the corporate sphere and how it fits in to unmet medical needs . I don’t know of any comparable review panels like this that have such a broad remit and bring together such a breadth of expertise which means that every review panel you come to you are getting a scientific education on all these different areas, which is great.”

The GWG reviews the projects for scientific merit: does the proposal seem plausible, does the team proposing it have the experience and expertise to do the work etc. The reviewers put in a lot of work ahead of time, not just reviewing the application, but looking at previous studies to see if the new application has evidence to support what this team hope to do, to compare it to other efforts in the same field. There are disagreements, but also a huge amount of respect for each other.

Once the GWG makes its recommendations on which projects to fund and which ones not to, the applications move to the CIRM Board, which has the final say on all funding decisions. The Board is given detailed summaries of each project, along with the recommendations of the GWG and our own CIRM Review team. But the Board is not told the identity of any of the applicants, those are kept secret to avoid even the appearance of any conflict of interest.

The Board is not required to follow the recommendations of the GWG, though they usually do. But the Board is also able to fund projects that the GWG didn’t place in the top tier of applications. They have done this on several occasions, often when the application targeted a disease or disorder that wasn’t currently part of the agency’s portfolio.

So that’s how Review works. The team, led by Dr. Gil Sambrano, does extraordinary work with little fanfare or fuss. But without them CIRM would be a far less effective agency.

The passage of Proposition 14 means we now have a chance to resume full funding of research, which means our Review team is going to be busier than ever. They have already started making changes to the application requirements. To help let researchers know what those changes are we are holding a Zoom webinar tomorrow, Thursday, at noon PST. If you would like to watch you can find it on our YouTube channel. And if you have questions you would like to ask send them to info@cirm.ca.gov

A Month of CIRM: Where we’ve been, where we’re going

All this month we are using our blog and social media to highlight a new chapter in CIRM’s life, thanks to the voters approving Proposition 14. We are looking back at what we have done since we were created in 2004, and also looking forward to the future. We kick off this event with a letter from our the Chair of our Board, Jonathan Thomas.

When voters approved Proposition 14 last November, they gave the Stem Cell Agency a new lease on life and a chance to finish the work we began with the approval of Proposition 71 in 2004. It’s a great honor and privilege. It’s also a great responsibility. But I think looking back at what we have achieved over the last 16 years shows we are well positioned to seize the moment and take CIRM and regenerative medicine to the next level and beyond.

When we started, we were told that if we managed to get one project into a clinical trial by the time our money ran out we would have done a good job. As of this moment we have 68 clinical trials that we have funded plus another 31 projects in clinical trials where we helped fund crucial early stage research. That inexorable march to therapies and cures will resume when we take up our first round of Clinical applications under Prop 14 in March.

But while clinical stage projects are the end game, where we see if therapies really work and are safe in people, there’s so much more that we have achieved since we were created. We have invested $900 million in  basic research, creating a pipeline of the most promising stem cell research programs, as well as investing heavily on so-called “translational” projects, which move projects from basic science to where they’re ready to apply to the Food and Drug Administration (FDA) to begin clinical trials.

We have funded more than 1,000 projects, with each one giving us valuable information to help advance the science. Our funding has helped attract some of the best stem cell scientists in the world to California and, because we only fund research in California, it has persuaded many companies to either move here or open offices here to be eligible for our support. We have helped create the Alpha Stem Cell Clinics, a network of leading medical centers around the state that have the experience and expertise to deliver stem cell therapies to patients. All of those have made California a global center in the field.

That result is producing big benefits for the state. An independent Economic Impact Analysis reported that by the end of 2018 we had already helped generate an extra $10.7 billion in new sales revenue and taxes for California, hundreds of millions more in federal taxes and created more than 56,000 new jobs.

As if that wasn’t enough, we have also:

  • Helped develop the largest iPSC research bank in the world.
  • Created the CIRM Center of Excellence in Stem Cell Genomics to accelerate fundamental understanding of human biology and disease mechanisms.
  • Helped fund the construction of 12 world class stem cell institutes throughout the state.
  • Reached a unique partnership with the National Heart, Lung and Blood Institutes to find a cure for sickle cell disease.
  • Used our support for stem cell research to leverage an additional $12 billion in private funding for the field.
  • Enrolled more than 2700 patients in CIRM funded clinical trials

In many ways our work is just beginning. We have laid the groundwork, helped enable an extraordinary community of researchers and dramatically accelerated the field. Now we want to get those therapies (and many more) over the finish line and get them approved by the FDA so they can become available to many more people around the state, the country and the world.

We also know that we have to make these therapies available to all people, regardless of their background and ability to pay. We have to ensure that underserved communities, who were often left out of research in the past, are an integral part of this work and are included in every aspect of that research, particularly clinical trials. That’s why we now require anyone applying to us for funding to commit to engaging with underserved communities and to have a written plan to show how they are going to do that.

Over the coming month, you will hear more about some of the remarkable things we have managed to achieve so far and get a better sense of what we hope to do in the future. We know there will be challenges ahead and that not everything we do or support will work. But we also know that with the team we have built at CIRM, the brilliant research community in California and the passion and drive of the patient advocate community we will live up to the responsibility the people of California placed in us when they approved Proposition 14.