CIRM funds clinical trials targeting heart disease, stroke and childhood brain tumors

Gary Steinberg (Jonathan Sprague)

Heart disease and stroke are two of the leading causes of death and disability and for people who have experienced either their treatment options are very limited. Current therapies focus on dealing with the immediate impact of the attack, but there is nothing to deal with the longer-term impact. The CIRM Board hopes to change that by funding promising work for both conditions.

Dr. Gary Steinberg and his team at Stanford were awarded almost $12 million to conduct a clinical trial to test a therapy for motor disabilities caused by chronic ischemic stroke.  While “clot busting” therapies can treat strokes in their acute phase, immediately after they occur, these treatments can only be given within a few hours of the initial injury.  There are no approved therapies to treat chronic stroke, the disabilities that remain in the months and years after the initial brain attack.

Dr. Steinberg will use embryonic stem cells that have been turned into neural stem cells (NSCs), a kind of stem cell that can form different cell types found in the brain.  In a surgical procedure, the team will inject the NSCs directly into the brains of chronic stroke patients.  While the ultimate goal of the therapy is to restore loss of movement in patients, this is just the first step in clinical trials for the therapy.  This first-in-human trial will evaluate the therapy for safety and feasibility and look for signs that it is helping patients.

Another Stanford researcher, Dr. Crystal Mackall, was also awarded almost $12 million to conduct a clinical trial to test a treatment for children and young adults with glioma, a devastating, aggressive brain tumor that occurs primarily in children and young adults and originates in the brain.  Such tumors are uniformly fatal and are the leading cause of childhood brain tumor-related death. Radiation therapy is a current treatment option, but it only extends survival by a few months.

Dr. Crystal Mackall and her team will modify a patient’s own T cells, an immune system cell that can destroy foreign or abnormal cells.  The T cells will be modified with a protein called chimeric antigen receptor (CAR), which will give the newly created CAR-T cells the ability to identify and destroy the brain tumor cells.  The CAR-T cells will be re-introduced back into patients and the therapy will be evaluated for safety and efficacy.

Joseph Wu Stanford

Stanford made it three in a row with the award of almost $7 million to Dr. Joe Wu to test a therapy for left-sided heart failure resulting from a heart attack.  The major issue with this disease is that after a large number of heart muscle cells are killed or damaged by a heart attack, the adult heart has little ability to repair or replace these cells.  Thus, rather than being able to replenish its supply of muscle cells, the heart forms a scar that can ultimately cause it to fail.  

Dr. Wu will use human embryonic stem cells (hESCs) to generate cardiomyocytes (CM), a type of cell that makes up the heart muscle.  The newly created hESC-CMs will then be administered to patients at the site of the heart muscle damage in a first-in-human trial.  This initial trial will evaluate the safety and feasibility of the therapy, and the effect upon heart function will also be examined.  The ultimate aim of this approach is to improve heart function for patients suffering from heart failure.

“We are pleased to add these clinical trials to CIRM’s portfolio,” says Maria T. Millan, M.D., President and CEO of CIRM.  “Because of the reauthorization of CIRM under Proposition 14, we have now directly funded 75 clinical trials.  The three grants approved bring forward regenerative medicine clinical trials for brain tumors, stroke, and heart failure, debilitating and fatal conditions where there are currently no definitive therapies or cures.”

A conversation with Bob Klein about the past, present and future of CIRM

Bob Klein

Anyone who knows anything about CIRM knows about Bob Klein. He’s the main author and driving force behind both Proposition 71 and Proposition 14, the voter-approved ballot initiatives that first created and then refunded CIRM. It’s safe to say that without Bob there’d be no CIRM.

Recently we had the great good fortune to sit down with Bob to chat about the challenges of getting a proposition on the ballot in a time of pandemic and electoral pandemonium, what he thinks CIRM’s biggest achievements are (so far) and what his future plans are.

You can hear that conversation in the latest episode of our podcast, “Talking ’bout (re) Generation”.

Enjoy.

CIRM Board Approves New Clinical Trial for ALS

This past Friday the governing Board of the California Institute for Regenerative Medicine (CIRM) awarded $11.99 million to Cedars-Sinai to fund a clinical trial for amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease. 

ALS is a neurodegenerative disease that results in the death of nerve cells in the brain and spinal cord, causing the muscles in the body to gradually weaken, leading to loss of limb function, difficulty breathing, paralysis, and eventually death.  There are medications that can slow down the progression of ALS, but unfortunately there is no cure for the disease.

Clive Svendsen, Ph.D., executive director of Cedars-Sinai’s Board of Governors Regenerative Medicine Institute, and his team will be conducting a trial that uses a combined cell and gene therapy approach as a treatment for ALS.  The trial builds upon the Stem Cell Agency’s first ALS trial, also conducted by Cedars-Sinai and Svendsen.

Genetically engineered stem cells will be transplanted into the motor cortex, an area of the brain responsible for voluntary movements.  These transplanted cells then become astrocytes, a type of support cell that help keep nerve cells functioning.  The astrocytes have been genetically altered to deliver high doses of a growth factor which has been shown to protect nerve cells.  The goal of this approach is to protect the upper motor neurons controlling muscle function and meaningfully improve the quality of life for ALS patients.

“ALS is a devastating disease that attacks the spinal cord and brain and results in the progressive loss of the ability to move, to swallow and eventually to breathe. ” says Maria T. Millan, M.D., President and CEO of CIRM.  “This clinical trial builds on Dr. Svendsen’s work previously funded by CIRM. We are fortunate to be able to support this important work, which was made possible by California citizens who voted to reauthorize CIRM under Proposition 14 this past November.”

Month of CIRM – Our Therapeutics Team Goes Hunting

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 have a guest blog by CIRM Senior Science Officer Lisa Kadyk, outlining how she and her colleagues actively search for the best science to fund.

Lisa Kadyk, Ph.D.

Hi everyone,

This is Lisa Kadyk, a Science Officer from the CIRM Therapeutics team, here to tell you about some of the work our team does to support the CIRM mission of accelerating stem cell treatments to patients with unmet medical needs.  Our job involves seeking out and recruiting great scientists to apply to CIRM and supporting those we fund.

Therapeutics team members manage both the awards that fund the final preclinical studies required before testing a therapeutic in a clinical trial (CLIN1), and the awards that fund the clinical trials themselves (CLIN2). 

I mentioned above that we actively recruit new applicants for our CLIN1 and CLIN2 awards – which is not an activity that is typical of most funding agencies – so why and how do we do this?  

It all comes down to our mission of accelerating the development of therapies to help patients with unmet medical needs.  It turns out that there are many potential applicants developing cutting edge therapies who don’t know much or anything about CIRM, and the ways we can help them with getting those therapies to the clinic and through clinical trials.    So, to bridge this gap, we Science Officers attend scientific conferences, read the scientific literature and meet regularly with each other to stay abreast of new therapeutic approaches being developed in both academia and industry, with the goal of identifying and reaching out to potential applicants about what CIRM has to offer. 

What are some of the things we tell potential applicants about how partnering with CIRM can help accelerate their programs?   First of all, due to the efforts of a very efficient Review team, CIRM is probably the fastest in the business for the time between application and potential funding.  It can be as short as three months for a CLIN1 or CLIN2 application to be reviewed by the external Grants Working Group and approved by the CIRM Board, whereas the NIH (for example) estimates it takes seven to ten months to fund an application.   Second, we have frequent application deadlines (monthly for CLIN1 and CLIN2), so we are always available when the applicant is ready to apply.  Third, we have other accelerating mechanisms in place to help grantees once they’ve received funding, such as the CIRM Alpha Stem Cell Clinics network of six clinical sites throughout California (more efficient clinical trial processes and patient recruitment) and Clinical Advisory Panels (CAPs) – that provide technical, clinical or regulatory expertise as well as patient advocate guidance to the grantee.  Finally, we Science Officers do our best to help every step of the way, from application through grant closeout.

We now feel confident that our recruitment efforts, combined with CIRM’s more efficient funding pipeline and review processes, are accelerating development of new therapies.  Back in 2016, a new CIRM Strategic Plan included the goal of recruiting 50 successful (i.e., funded) clinical trial applicants within five years.  This goal seemed like quite a stretch, since CIRM had funded fewer than 20 clinical trials in the previous ten years.  Fast-forward to the end of 2020, and CIRM had funded 51 new trials in those five years, for a grand total of 68 trials.    

Now, with the passage of Proposition 14 this past November, we are looking forward to bringing more cell and gene therapeutic candidates into clinical trials.   If you are developing one yourself, feel free to let us know… or don’t be surprised if you hear from us!  

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.

Inspiring new documentary about stem cell research

Poster for the documentary “Ending Disease”

2020 has been, to say the very least, a difficult and challenging year for all of us. But while the focus of the world has, understandably, been on the coronavirus there was also some really promising advances in stem cell research. Those advances are captured in a great new documentary called Ending Disease.

The documentary is by Emmy award-winning filmmaker Joe Gantz. In it he follows ten people who are facing life-threatening or life-changing diseases and injuries and who turn to pioneering stem cell therapies for help.

It’s an inspiring documentary, one that reminds you of the real need for new treatments and the tremendous hope and promise of stem cell therapies. Here’s a look at a trailer for Ending Disease.

You can see an exclusive screening of Ending Disease on Friday, January 8th, 2021 at 5:00pm PST.

After the livestream, there will be a live Q&A session where former members of the successful Proposition 14 campaign team – which refunded CIRM with an additional $5.5 billion – will be joined by CIRM’s President and CEO Dr. Maria Millan, talking about what lies ahead for CIRM and the future of stem cell research.

To purchase a ticket, click here. It only costs $12 and 50% of the ticket sales proceeds will go to Americans for Cures to help them continue to advocate for the advancement of stem cell research, and more importantly, for the patients and families to whom stem cell research provides so much hope.

If you need any extra persuading that it’s something you should definitely put on our calendar, here’s a letter from the film maker Joe Gantz.

I am the director of the documentary Ending Disease: The Stem Cell, Anti-Cancer T-Cell, & Antibody Revolution In Medicine, a film that will help inform people about the progress that’s been made in this field and how people with their lives on the line are now able to benefit from these new regenerative therapies. 

I was granted unprecedented access to ten of the first generation of clinical trials using stem cell and regenerative medicine to treat and cure many of the most devastating diseases and conditions including: brain cancer, breast cancer, leukemia and lymphoma, HIV, repairing a broken spinal cord, retinitis pigmentosa and SCID. The results are truly inspiring.

This is personal for me.  After spending four years making this documentary, I was diagnosed with bladder cancer. Upon diagnosis, I immediately felt the same desperation as millions of families who are in search of a medical breakthrough. I understood, on a personal level, what the patients we followed in the film all knew: when you are diagnosed with a disease, there is a narrow window of time in which you can effectively seek a life-saving treatment or cure. If treatment becomes available outside of that window, then it is too late. However, Ending Disease shows that with continued support for regenerative medicine, we can create a near future in which one-time cures and highly mitigating therapies are available to patients for a whole host of diseases.

Best regards,

Joe

Much to be Thankful for

It’s traditional this time of year to send messages of gratitude to friends and family and colleagues. And we certainly have much to be thankful for.

Thanks to the voters of California, who passed Proposition 14, we have a bright, and busy, future. We have $5.5 billion to continue our mission of accelerating stem cell treatments to patients with unmet medical needs.

That means the pipeline of promising projects that we have supported from an early stage can now apply to us to help take that work out of the lab and into people.

It means research areas, particularly early-stage work, where we had to reduce our funding as we ran out of money can now look forward to increased support.

It means we can do more to bring this research, and it’s potential benefits, to communities that in the past were overlooked.

We have so many people to thank for all this. The scientists who do the work and championed our cause at the ballot box. The voters of California who once again showed their support for and faith in science. And the patients and patient advocates, the reason we were created and the reason we come to work every day.

As Dr. Maria Millan, our President & CEO, said in a letter to our team; “We are continually faced by great opportunities brilliantly disguised as insoluble problems.”  Here’s to the opportunities made possible by CIRM and for its continuation made possible by Prop 14!”

And none of this would be possible without the support of all of you. And for that we are truly Thankful.

From everyone at CIRM, we wish you a happy, peaceful and safe Thanksgiving.

Thank you

Bob Klein

These last few days have been interesting on so many levels. First the presidential race has kept the nation on tenterhooks. Closer to home the vote count for Proposition 14, to refunded CIRM, has been painstakingly slow (by the way, painstakingly means “with great care and thoroughness” for which we thank all the vote counters). But now, finally, happily, we have a verdict.

WE WON.

 It was close, desperately so. In the end the Associated Press called the race with the count at 51% yes, to 49% no. You can understand why so many of us were so nervous for so long. But now we have something to celebrate.

As Jonathan Thomas, JD, PhD, the Chair of our Board said: “We are thrilled to see Proposition 14 approved by the voters of California. We are proud of what we have achieved so far – the cures and therapies we helped develop, the billions we brought into the state in additional investments, and the tens of thousands of jobs we created – and we look forward to continuing that work.

“We are honored by the trust the people of California have placed in us, and by the support of our extraordinary patient advocate community and by the many Chambers of Commerce around California who have all recognized our historic achievements.

“We are already working on ways to repay that trust and bring stem cell and regenerative therapies to all the people of this great state, particularly for communities that have traditionally been overlooked or underserved.” 

In a news release on the Californians for Cures website, Bob and Danielle Klein, who led the Yes on 14 campaign, were understandably delighted:  

“The success of Prop. 14 sends a clear message from California voters that one of the most important investments our state can make is in the future health of our families. Over the past decade, California has made incredibly thoughtful and impactful investments in developing stem cell therapies and cures for diseases and conditions like diabetes, cancer, blindness, Parkinson’s, paralysis and many more; now we know this progress and work to mitigate human suffering, restore health and improve the human condition will continue. A special thank you to California’s voters and our supporters in passing this critical measure. Today would not have been possible without our historically unprecedented coalition of patient advocate organizations and individuals – the heart and soul of this campaign – who worked tirelessly to overcome all obstacles and help secure a victory for patients and their families, and deliver hope to those searching for a cure for generations to come.”

To all of you who voted for us, thank you from the bottom of our hearts.

To all the people who worked so hard to get Prop 14 passed, thank you. We are indebted to you.

OK, gotta go. We have work to do.