What are the latest advances in stem cell research targeting cancer? Can stem cells help people battling COVID-19 or even help develop a vaccine to stop the virus? What are researchers and the scientific community doing to help address the unmet medical needs of underserved communities? Those are just a few of the topics being discussed at the Annual CIRM Alpha Stem Cell Clinic Network Symposium on Thursday, October 8th from 9am to 1.30pm PDT.
Like pretty nearly everything these days the symposium is going to be a virtual event, so you can watch it from the comfort of your own home on a phone or laptop. And it’s free.
The CIRM Alpha Clinics are a network of leading medical centers here in California. They specialize in delivering stem cell and gene therapies to patients. So, while many conferences look at the promise of stem cell therapies, here we deal with the reality; what’s in the clinic, what’s working, what do we need to do to help get these therapies to patients in need?
It’s a relatively short meeting, with short presentations, but that doesn’t mean it will be short on content. Some of the best stem cell researchers in the U.S. are taking part so you’ll learn an awful lot in a short time.
We’ll hear what’s being done to find therapies for
Rare diseases that affect children
Type 1 diabetes
We’ll discuss how to create a patient navigation system that can address social and economic determinants that impact patient participation? And we’ll look at ways that the Alpha Clinic Network can partner with community care givers around California to increase patient access to the latest therapies.
It’s going to be a fascinating day. And did I mention it’s free!
One of our favorite things to do at CIRM is deliver exciting news about CIRM projects. This usually entails discussion of recent discoveries that made headlines, or announcing the launch of a new CIRM-funded clinical trial …. tangible signs of progress towards addressing unmet medical needs through advances in stem technology.
But there are equally exciting signs of progress that are not always so obvious to the untrained eye- those that we are privileged to witness behind the scenes at CIRM. These efforts don’t always lead to a splashy news article or even to a scientific publication, but they nonetheless drive the evolution of new ideas and can help steer the field away from futile lines of investigation. Dozens of such projects are navigating uncharted waters by filling knowledge gaps, breaking down technical barriers, and working closely with regulatory agencies to define novel and safe paths to the clinic.
These efforts can remain “hidden” because they are in the intermediate stages of the long, arduous and expensive journey from “bench to beside”. For the pioneering projects that CIRM funds, this journey is unique and untrod, and can be fraught with false starts. But CIRM has developed tools to track the momentum of these programs and provide continuous support for those with the most promise. In so doing, we have watched projects evolve as they wend their way to the clinic. We wanted to share a few examples of how we do this with our readers, but first… a little background for our friends who are unfamiliar with the nuts and bolts of inventing new medicines.
A common metaphor for bringing scientific discoveries to market is a pipeline, which begins in a laboratory where a discovery occurs, and ends with government approval to commercialize a new medicine, after it is proven to be safe and effective. In between discovery and approval is a stage called “Translation”, where investigators develop ways to transition their “research level” processes to “clinically compatible” ones, which only utilize substances that are of certified quality for human use.
Investigators must also work out novel ways to manufacture the product at larger scale and transition the methods used for testing in animal models to those that can be implemented in human subjects.
A key milestone in Translation is the “preIND” (pre Investigational New Drug (IND) meeting, where an investigator presents data and plans to the US Food and Drug Administration (FDA) for feedback before next stage of development begins, the pivotal testing needed to show it is both safe and effective.
These “IND enabling studies” are rigorous but necessary to support an application for an IND and the initiation of clinical trials, beginning with phase 1 to assess safety in a small number of individuals, and phase 2, where an expanded group is evaluated to see if the therapy has any benefits for the patient. Phase 3 trials are studies of very large numbers of individuals to gain definitive evidence of safety and therapeutic effect, generally the last step before applying to the FDA for market approval. An image of the pipeline and the stages described are provided in our diagram below.
The pipeline can be notoriously long and tricky, with plenty of twists, turns, and unexpected obstacles along the way. Many more projects enter than emerge from this gauntlet, but as we see from these examples of ‘works in progress”, there is a lot of momentum building.
Caption for Graphic:This graphic shows the number of CIRM-funded projects and the stages they have progressed through multiple rounds of CIRM funding. For example, the topmost arrow shows that are about 19 projects at the translational stage of the pipeline that received earlier support through one of CIRM’s Discovery stage programs. Many of these efforts came out of our pre-2016 funding initiatives such as Early Translation, Basic Biology and New Faculty Awards. In another example, you can see that about 15 awards that were first funded by CIRM at the IND enabling stage have since progressed into a phase 1 or phase 2 clinical trials. While most of these efforts also originated in some of CIRM’s pre-2016 initiatives such as the Disease Team Awards, others have already progressed from CIRM’s newer programs that were launched as part of the “2.0” overhaul in 2016 (CLIN1).
The number of CIRM projects that have evolved and made their way down the pipeline with CIRM support is impressive, but it is clearly an under-representation, as there are other projects that have progressed outside of CIRM’s purview, which can make things trickier to verify.
We also track projects that have spun off or been licensed to commercial organizations, another very exciting form of “progression”. Perhaps those will contribute to another blog for another day! In the meantime, here are a just a few examples of some of the progressors that are depicted on the graphic.
Project: stem cell therapy to enhance bone healing in theelderly
– Currently funded stage: IND enabling development, CLIN1-11256 (Dr. Zhu, Ankasa Regenerative Therapeutics)
While most people probably wouldn’t put 2020 in their list of favorite years, it’s certainly turning out to be a good one for jCyte. Earlier this year jCyte entered into a partnership with global ophthalmology company Santen Pharmaceuticals worth up to $252 million. Then earlier this week they announced some encouraging results from their Phase 2b clinical trial.
Let’s back up a bit and explain what jCyte does and why it’s so important. They have developed a therapy for retinitis pigmentosa (RP), a rare vision destroying disease that attacks the light sensitive cells at the back of the eye. People are often diagnosed when they are in their teens and most are legally blind by middle age. CIRM has supported this therapy from its early stages into clinical trials.
This latest clinical trial is one of the largest of its kind anywhere in the world. They enrolled 84 patients (although only 74 were included in the final analysis). The patients had vision measuring between 20/80 and 20/800. They were split into three groups: one group was given a sham or placebo treatment; one was given three million human retinal progenitor cells (hRPCs), the kind attacked by the disease; and one was given six million hRPCs.
In an article in Endpoints News, jCyte’s CEO Paul Bresge said there was a very specific reason for this approach. “We did enroll a very wide patient population into our Phase IIb, including patients that had vision anywhere from 20/80 to 20/800, just to learn which patients would potentially be the best responders.”
The results showed that the treatment group experienced improved functional vision and greater clarity of vision compared to the sham or placebo group. Everyone had their vision measured at the start and again 12 months later. For the placebo group the mean change in their ability to read an eye chart (with glasses on) was an improvement of 2.81 letters; for the group that got three million hRPCs it was 2.96 letters, and for the group that got six million hRPCs it was 7.43 letters.
When they looked at a very specific subgroup of patients the improvement was even more dramatic, with the six million cell group experiencing an improvement of 16.27 letters.
Dr. Henry Klassen, one of the founders of jCyte, says the therapy works by preserving the remaining photoreceptors in the eye, and helping them bounce back.
“Typically, people think about the disease as a narrowing of this peripheral vision in a very nice granular way, but that’s actually not what happens. What happens in the disease is that patients lose like islands of vision. So, what we’re doing in our tests is actually measuring […] islands that the patients have at baseline, and then what we’re seeing after treatment is that the islands are expanding. It’s similar to the way that one would track, let’s say a tumor, in oncology of course we’re looking for the opposite effect. We’re looking for the islands of vision to expand.”
One patient did experience some serious side effects in the trial but they responded well to treatment.
The team now plan on carrying out a Phase 3 clinical trial starting next year. They hope that will provide enough evidence showing the treatment is both safe and effective to enable them to get approval from the US Food and Drug Administration to make it available to all who need it.
At CIRM we don’t just invest in stem cell research, we invest in people. One prime example of that is our Bridges to Stem Cell Research program. This is helping train the next generation of scientists by preparing Californian undergraduate and master’s students for careers in stem cell research.
The students who go through the Bridges program get up to a year-long internship, hands-on training and education in stem cell research. Just as importantly, they also get to work directly with patients to help them understand why we do this work; to help people in need.
One of our recent
Bridges graduates is Zach Wagoner. Zach was a biology student and wondering what
to do next to help him get some experience for a job when someone told him
about the Bridges program. That set him on a course that is changing his life.
So how did the random conversation impact Zach? The team at the UC Irvine Sue and Bill Gross Stem Cell Research Center shot this video to answer that question.
It’s not just Zach who benefited from the program. Of the 1257 alumni who graduated from the program by March of this year:
50% are working full time in academic or
biotech research related positions
Battling cancer is always a balancing act. The methods we use – surgery, chemotherapy and radiation – can help remove the tumors but they often come at a price to the patient. In cases where the cancer has spread to the bone the treatments have a limited impact on the disease, but their toxicity can cause devastating problems for the patient. Now, in a CIRM-supported study, researchers at UC Irvine (UCI) have developed a method they say may be able to change that.
Bone metastasis –
where cancer starts in one part of the body, say the breast, but spreads to the
bones – is one of the most common complications of cancer. It can often result
in severe pain, increased risk of fractures and compression
of the spine. Tackling them is difficult because some cancer cells can
alter the environment around bone, accelerating the destruction of healthy bone
cells, and that in turn creates growth factors that stimulate the growth of the
cancer. It is a vicious cycle where one problem fuels the other.
Now researchers at
UCI have developed a method where they combine engineered mesenchymal stem cells (taken from the bone marrow) with
targeting agents. These act like a drug delivery device, offloading
different agents that simultaneously attack the cancer but protect the bone.
In a news release Weian Zhao, lead author of the study, said:
“What’s powerful about this
strategy is that we deliver a combination of both anti-tumor and anti-bone
resorption agents so we can effectively block the vicious circle between
cancers and their bone niche. This is a safe and almost nontoxic treatment
compared to chemotherapy, which often leaves patients with lifelong issues.”
published in the journal EBioMedicine,
has already been shown to be effective in mice. Next, they hope to be able to
do the safety tests to enable them to apply to the Food and Drug Administration
for permission to test it in people.
The team say if this
approach proves effective it might also be used to help treat other bone-related
diseases such as osteoporosis and multiple myeloma.
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
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?
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
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.
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.
If you were looking for a poster child for an unmet medical need Huntington’s disease (HD) would be high on the list. It’s a devastating disease that attacks the brain, steadily destroying the ability to control body movement and speech. It impairs thinking and often leads to dementia. It’s always fatal and there are no treatments that can stop or reverse the course of the disease. Today the Board of the California Institute for Regenerative Medicine (CIRM) voted to support a project that shows promise in changing that.
The Board voted to approve $6 million to enable Dr. Leslie Thompson and her team at the University of California, Irvine to do the late stage testing needed to apply to the US Food and Drug Administration for permission to start a clinical trial in people. The therapy involves transplanting stem cells that have been turned into neural stem cells which secrete a molecule called brain-derived neurotrophic factor (BDNF), which has been shown to promote the growth and improve the function of brain cells. The goal is to slow down the progression of this debilitating disease.
“Huntington’s disease affects around 30,000 people in the US and children born to parents with HD have a 50/50 chance of getting the disease themselves,” says Dr. Maria T. Millan, the President and CEO of CIRM. “We have supported Dr. Thompson’s work for a number of years, reflecting our commitment to helping the best science advance, and are hopeful today’s vote will take it a crucial step closer to a clinical trial.”
Another project supported by CIRM at an earlier stage of research was also given funding for a clinical trial.
The Board approved almost $12 million to support a clinical trial to help people undergoing a kidney transplant. Right now, there are around 100,000 people in the US waiting to get a kidney transplant. Even those fortunate enough to get one face a lifetime on immunosuppressive drugs to stop the body rejecting the new organ, drugs that increase the risk for infection, heart disease and diabetes.
Dr. Everett Meyer, and his team at Stanford University, will use a combination of healthy donor stem cells and the patient’s own regulatory T cells (Tregs), to train the patient’s immune system to accept the transplanted kidney and eliminate the need for immunosuppressive drugs.
The initial group targeted in this clinical trial are people with what are called HLA-mismatched kidneys. This is where the donor and recipient do not share the same human leukocyte antigens (HLAs), proteins located on the surface of immune cells and other cells in the body. Around 50 percent of patients with HLA-mismatched transplants experience rejection of the organ.
In his application Dr. Meyer said they have a simple goal: “The goal is “one kidney for life” off drugs with safety for all patients. The overall health status of patients off immunosuppressive drugs will improve due to reduction in side effects associated with these drugs, and due to reduced graft loss afforded by tolerance induction that will prevent chronic rejection.”
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.
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
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.
The newest member of the CIRM Board is a researcher who wasn’t always sure she would have a career as a scientist. Suzanne Sandmeyer, PhD, says at the start of her career she had a lot of doubts.
“During my postdoc, I was developing the impression I would struggle to survive in my career as a scientist. I had a female mentor at the time and I shared this idea with her. She told me that was ridiculous: I was not going to starve, and I believed her. Turns out, she was right. Today, I enjoy the independence that comes with academia.”
We’re delighted she changed her mind. Dr. Sandmeyer, is now the Vice Dean for Research at the University of California at Irvine (UCI) School of Medicine, and has been appointed to CIRM’s Board.
She was recommended for the position by UCI Chancellor Howard Gillman who called her “an outstanding researcher who has contributed significantly to the field of molecular genetics.”
Dr. Sandmeyer said she was honored to be chosen.
“It is a privilege to be involved in this new era of stem cell research and clinical trials. We have only just begun to understand the potential of our discoveries and the impact we can have on human health by advancing stem cell therapies.”
Jonathan Thomas, Ph.D., J.D., the Chair of the CIRM Board, welcomed the appointment saying:
“Dr. Sandmeyer will be a great addition to the Board. She has a distinguished career, not just as a highly regarded scientist but also as a leader in helping UC Irvine become the great research institution it is today.”
Dr. Sandmeyer’s career as a scientist had an early beginning.
“My Dad was an engineer, so science always seemed like a very natural thing to pursue. Growing up I liked to be outdoors and loved the diversity of living things, so I eventually gravitated toward biology.”
That sense of curiosity and love of biology has helped her build a bustling and productive research lab at UC Irvine. Her research focuses on molecular genetics and biochemistry of retrovirus-like elements called retrotransposons (which make up almost half the human genome but are not well understood) and metabolic engineering in yeast. Although she has had amazing success in academia, she was not always sure that this would be her path.
As a member of the CIRM Board, Dr. Sandmeyer will provide important insight and perspective into advancing stem cell therapies.
“Our country has one of the most expensive systems of medical care and yet we don’t have the longest-lived population. I want to work toward reducing the burden of medical expenses for people. I am very excited about the potential of stem cells to treat many disorders and the potential for new technologies like CRISPR to further empower that approach.”
When not making important scientific discoveries in the lab, you can find Dr. Sandmeyer pursuing one of her many and varied hobbies.
“I go through phases like everyone. There is never enough time. My favorites are astronomy, bird photography, guitar, biking, kayaking, reading and of course German shepherd dogs.”