Today the governing Board of the California Institute for
Regenerative Medicine (CIRM) awarded $11.08 Million to Dr. Peter Stock at the
University of California San Francisco (UCSF) to conduct a clinical trial for
treatment of Type 1 Diabetes (T1D).
award brings the total number of CIRM funded clinical trials to 54.
T1D is a chronic autoimmune disease that affects
approximately 1.25 million Americans, with 40,000 new diagnoses each year. T1D occurs as a result of the body’s immune
system destroying its own pancreatic beta cells. These cells are necessary to produce the
vital hormone insulin, which regulates blood sugar levels in the body. As a result of a lack of insulin, there is no
blood sugar control in T1D patients, gradually causing disabling and
life-threatening complications such as heart disease, nerve damage, and vision
There is no cure for T1D.
Current treatments consist of blood sugar monitoring and multiple daily
injections of insulin. Transplantation of
beta cells, contained in donor pancreatic islets, can reverse the symptoms of
diabetes. However, due to a poor islet survival
rate, transplants require islets from multiple donors. Furthermore, since islet cells are
transplanted directly into the vessels that enter the liver, it is extremely
difficult to monitor and retrieve these cells should the need arise.
Dr. Stock’s clinical trial at UCSF aims to address these
limitations. The trial will be using parathyroid
glands to aid in the success and viability of the transplant procedure. Co-transplantation of islets and parathyroid
glands, from the same donor, substantially increases beta cell survival, potentially
enabling adequate long-term insulin production and removing the need for
multiple donors. Additionally, the
co-transplantation will occur in the patient’s forearm, which allows for easier
monitoring and improves the effectiveness and accessibility of islet
transplants for patients.
“This team’s innovative approach to develop a definitive
cell-based treatment for Type 1 Diabetes has the potential to address an unmet
medical need that exists despite advancements in diabetes therapy.” says
Maria T. Millan, M.D., the President and CEO of CIRM. “The success of this clinical trial could
enable the successful application of islet cell transplants but also of future stem-cell
based approaches for diabetes.”
CIRM has funded three other clinical trials for T1D. One of these was conducted by Caladrius Biosciences and two by ViaCyte, Inc.
At CIRM we are very cautious about using the “c” word. Saying someone has been “cured” is a powerful statement but one that loses its meaning when over used or used inappropriately. However, in the case of a new study from U.C. San Francisco and St. Jude Children’s Research Hospital in Memphis, saying “cure” is not just accurate, it’s a celebration of something that would have seemed impossible just a few years ago.
The research focuses on children with a specific form of Severe Combined Immunodeficiency (SCID) called X-Linked SCID. It’s also known as “bubble baby” disease because children born with this condition lack a functioning immune system, so even a simple infection could be fatal and in the past they were kept inside sterile plastic bubbles to protect them.
In this study, published in the New England Journal of Medicine, researchers took blood stem
cells from the child and, in the lab, genetically re-engineered them to correct
the defective gene, and then infused them back into the child. Over time they
multiplied and created a new blood supply, one free of the defect, which helped
repair the immune system.
In a news
release Dr. Ewelina Mamcarz, the lead author of the study, announced that
ten children have been treated with this method.
“These patients are toddlers now, who are responding to
vaccinations and have immune systems to make all immune cells they need for
protection from infections as they explore the world and live normal lives.
This is a first for patients with SCID-X1.”
The ten children were treated at both St. Jude and at UCSF
funded the UCSF arm of the clinical trial.
The story, not surprisingly, got a lot of attention in the
media including this fine
piece by CNN.
On the surface, actor Michael J. Fox, singer Neil Diamond, civil rights activist Jesse Jackson and Scottish comedian Billy Connolly would appear to have little in common. Except for one thing. They all have Parkinson’s Disease (PD).
Their celebrity status has helped raise public awareness about the condition, but studies show that awareness doesn’t amount to an understanding of PD or the extent to which it impacts someone’s life. In fact a study in the UK found that many people still don’t think PD is a serious condition.
To try and help change that people around the world will be
holding events today, April 11th, World Parkinson’s Day.
The disease was first described by James Parkinson in 1817 in “An Essay on the Shaking Palsy”. In the essay Parkinson described a pattern of trembling in the hands and fingers, slower movement and loss of balance. Our knowledge about the disease has advanced in the last 200 years and now there are treatments that can help slow down the progression of the disease. But those treatments only last for a while, and so there is a real need for new treatments.
That’s what Jun Takahashi’s team at Kyoto University in
Japan hope to provide. In a first-of-its-kind procedure they took skin cells
from a healthy donor and reprogrammed them to become induced pluripotent stem
cells (iPSCs), or stem cells that become any type of cell. These iPSCs were
then turned into the precursors of dopamine-producing neurons, the cells
destroyed by PD, and implanted into 12 brain regions known to be hotspots for
was carried out in October and the patient, a male in his 50s, is still
healthy. If his symptoms continue to improve and he doesn’t experience any bad
side effects, he will receive a second dose of dopamine-producing stem
cells. Six other patients are scheduled to receive this same treatment.
Earlier tests in monkeys showed that the implanted stem cells improved Parkinson’s symptoms without causing any serious side effects.
Scientists at UC San
Francisco are trying a different approach, using gene therapy to tackle one of
the most widely recognized symptoms of PD, muscle movement.
In the study,
published in the journal Annals
of Neurology, the team used
an inactive virus to deliver a gene to boost production of dopamine in the
brain. In a Phase 1 clinical trial 15 patients, whose medication was no longer
able to fully control their movement disorder, were treated with this approach.
Not only were they able to reduce their medication – up to 42 percent in some
cases – the medication they did take lasted longer before causing dyskinesia,
an involuntary muscle movement that is a common side effect of the PD
In a news article Dr. Chad Christine, the first author of the
study, says this approach may also help reduce other symptoms.
“Since many patients were able to substantially
reduce the amount of Parkinson’s medications, this gene therapy treatment may
also help patients by reducing dose-dependent side effects, such as sleepiness
At CIRM we have
a long history of funding research into PD. Over the years we have invested
more than $55 million to try and develop new treatments for the disease.
In June 2018, the CIRM Board awarded $5.8 million to UC San Francisco’s Krystof Bankiewicz and Cedars-Sinai’s Clive Svendsen. They are using neural progenitor cells, which have the ability to multiply and turn into other kinds of brain cells, and engineering them to express the growth factor GDNF which is known to protect the cells damaged in PD. The hope is that when transplanted into the brain of someone with PD, it will help slow down, or even halt the progression of the disease.
The CIRM funding
will hopefully help the team do the pre-clinical research needed to get the
FDA’s go-ahead to test this approach in a clinical trial.
At the time of the award David Higgins, PhD, the CIRM Board Patient Advocate for Parkinson’s Disease, said: “One of the big frustrations for people with Parkinson’s, and their families and loved ones, is that existing therapies only address the symptoms and do little to slow down or even reverse the progress of the disease. That’s why it’s important to support any project that has the potential to address Parkinson’s at a much deeper, longer-lasting level.”
But we don’t just fund the research, we try to bring the scientific community together to help identify obstacles and overcome them. In March of 2013, in collaboration with the Center for Regenerative Medicine (CRM) of the National Institutes of Health (NIH), we held a two-day workshop on cell therapies for Parkinson’s Disease. The experts outlined the steps needed to help bring the most promising research to patients.
Around one million Americans are currently living with Parkinson’s Disease. Worldwide the number is more than ten million. Those numbers are only expected to increase as the population ages. There is clearly a huge need to develop new treatments and, hopefully one day, a cure.
Till then days like April 11th will be an
opportunity to remind ourselves why this work is so important.
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.
More often than not, people don’t really think about their blood sugar levels before sitting down to enjoy a delicious meal, partake in a tasty dessert, or go out for a bicycle ride. But for type 1 diabetes (T1D) patients, every minute and every action revolves around the readout from a glucose meter, a device used to measure blood sugar levels.
Normally, the pancreas contains beta cells that produce insulin in order to maintain blood sugar levels in the normal range. Unfortunately, those with T1D have an immune system that destroys their own beta cells, thereby decreasing or preventing the production of insulin and in turn the regulation of blood sugar levels. Chronic spikes in blood sugar levels can lead to blindness, nerve damage, kidney failure, heart disease, stroke, and even death.
Those with T1D manage their condition by injecting themselves with insulin anywhere from two to four times a day. A light workout, slight change in diet, or even an exciting event can have a serious impact that requires a glucose meter check and an insulin injection.
There are clinical trials involving transplants of pancreatic “islets”, clusters of cells containing healthy beta cells, but these rely on pancreases from deceased donors and taking immune suppressing drugs for life.
But what if there was a way to produce healthy beta cells in a lab without the need of a transplant?
Dr. Matthias Hebrok, director of the UCSF diabetes center, and Dr. Gopika Nair, postdoctoral fellow, have discovered how to transform human stem cells into healthy, insulin producing beta cells.
In a news release written by Dr. Nicholas Weiler of UCSF, Dr. Hebrok is quoted as saying “We can now generate insulin-producing cells that look and act a lot like the pancreatic beta cells you and I have in our bodies. This is a critical step towards our goal of creating cells that could be transplanted into patients with diabetes.”
For the longest time, scientists could only produce cells at an immature stage that were unable to respond to blood sugar levels and secrete insulin properly. Dr. Hebrok and Dr. Nair discovered that mimicking the “islet” formation of cells in the pancreas helped the cells mature. These cells were then transplanted into mice and found that they were fully functional, producing insulin and responding to changes blood sugar levels.
Dr. Hebrok’s team is already in collaboration with various colleagues to make these cells transplantable into patients.
Dr. Nair in the article is also quoted as saying “Current therapeutics like insulin injections only treat the symptoms of the disease. Our work points to several exciting avenues to finally finding a cure.”
“We’re finally able to move forward on a number of different fronts that were previously closed to us,” Hebrok added. “The possibilities seem endless.”
CIRM has funded three separate human clinical trials for T1D that total approximately $37.8 million in awards. Two of these trials are being conducted by ViaCyte, Inc. and the third trial is being conducted by Caladrius Biosciences.
It’s hard to sum up the activities and achievements of a year in a single document, let alone one that’s just 24 pages. But that’s what we have done in putting together our 2018 Annual Report.
It’s a look back at the year just gone, the highlights, the low lights (spoiler alert – there weren’t any) and the impact we had on the field of stem cell research. But it’s far more than that. It’s also a look ahead. A look at the challenges we face, and profiles of the people who are going to help us overcome those challenges and maintain our progress.
And people are truly at the heart of this report, from UC San Francisco’s Dr. Tippi MacKenzie who is on the front cover for her work in developing an in-utero treatment for the almost always fatal disorder alpha thalassemia major (and the photo of the baby and mom whose lives were changed by that therapy) to Rich Lajara on the back cover, the first person ever treated in a CIRM-funded clinical trial.
Inside are an array of simple images designed to reflect how we as a state agency have performed this year. The numbers themselves tell a powerful story:
50 clinical trials funded to date, 7 this year alone
$2.6 billion in CIRM grants has been leveraged to bring in an additional $3.2 billion in matching funds and investments from other sources.
1,180 patients have been involved in CIRM clinical trials
We know people don’t have a lot of time to read Annual Reports so we have made this as visually engaging and informative as possible. We want you to get a real sense of who we are, what we have done and who has helped us do that without you having to wade through a document the size of War and Peace (great book by the way – the Russians beat Napoleon).
We think we have a great story to tell. This Annual Report is one chapter in that story. We hope you like it.
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.
There are more than 200,000 cases of traumatic brain injury (TBI) in the US every year. The injuries can be devastating, resulting in everything from difficult sleeping to memory loss, depression and severe disability. There is no cure. But this week the SanBio Group had some encouraging news from its Phase 2 STEMTRA clinical trial.
In the trial patients with TBI were given stem cells, derived from the bone marrow of healthy adult donors. When transplanted into the area of injury in the brain, these cells appear to promote recovery by stimulating the brain’s own regenerative ability.
In this trial the cells demonstrated what the company describes as “a statistically significant improvement in their motor function compared to the control group.”
Endometriosis is an often painful condition that is caused when the cells that normally line the inside of the uterus grow outside of it, causing scarring and damaging other tissues. Over time it can result in severe pain, infertility and increase a woman’s risk for ovarian cancer.
There is no effective long-term treatment but now researchers at Northwestern Medicine have developed an approach, using the woman’s own cells, that could help treat the problem.
The researchers took cells from women, turned them into iPS pluripotent stem cells and then converted those into healthy uterine cells. In laboratory tests these cells responded to the progesterone, the hormone that plays a critical role in the uterus.
In a news release, Dr. Serdar Bulun, a senior author of the study, says this opens the way to testing these cells in women:
“This is huge. We’ve opened the door to treating endometriosis. These women with endometriosis start suffering from the disease at a very early age, so we end up seeing young high school girls getting addicted to opioids, which totally destroys their academic potential and social lives.”
A lot of the research we write about on the Stem Cellar focuses on potential treatments or new approaches that show promise. So every once in a while, it’s good to remind ourselves that there are already stem cell treatments that are not just showing promise, they are saving lives.
That is the case with Ja’Ceon Golden. Regular readers of our blog know that Ja’Ceon was diagnosed with Severe Combined Immunodeficiency (SCID) also known as “bubble baby disease” when he was just a few months old. Children born with SCID often die in the first few years of life because they don’t have a functioning immune system and so even a simple infection can prove life-threatening.
Today he is a healthy, happy, thriving young boy. These pictures, taken by his great aunt Dannie Hawkins, including one of him in his Halloween costume, show how quickly he is growing. And all thanks to some amazing researchers, an aunt who wouldn’t give up on him, and the support of CIRM.
While we have made great progress in developing therapies that control the AIDS virus, HIV/AIDS remains a chronic condition and HIV medicines themselves can give rise to a new set of medical issues. That’s why the Board of the California Institute for Regenerative Medicine (CIRM) has awarded $3.8 million to a team from City of Hope to develop an HIV immunotherapy.
The City of Hope team, led by Xiuli Wang, is developing a chimeric antigen receptor T cell or CAR-T that will enable them to target and kill HIV Infection. These CAR-T cells are designed to respond to a vaccine to expand on demand to battle residual HIV as required.
CIRM Board member Jeff Sheehy
Jeff Sheehy, a CIRM Board member and patient advocate for HIV/AIDS, says there is a real need for a new approach.
“With 37 million people worldwide living with HIV, including one million Americans, a single treatment that cures is desperately needed. An exciting feature of this approach is the way it is combined with the cytomegalovirus (CMV) vaccine. Making CAR T therapies safer and more efficient would not only help produce a new HIV treatment but would help with CAR T cancer therapies and could facilitate CAR T therapies for other diseases.”
This is a late stage pre-clinical program with a goal of developing the cell therapy and getting the data needed to apply to the Food and Drug Administration (FDA) for permission to start a clinical trial.
The Board also approved three projects under its Translation Research Program, this is promising research that is building on basic scientific studies to hopefully create new therapies.
$5.068 million to University of California at Los Angeles’ Steven Schwartz to use a patient’s own adult cells to develop a treatment for diseases of the retina that can lead to blindness
$4.17 million to Karin Gaensler at the University of California at San Francisco to use a leukemia patient’s own cells to develop a vaccine that will stimulate their immune system to attack and destroy leukemia stem cells
Almost $4.24 million to Stanford’s Ted Leng to develop an off-the-shelf treatment for age-related macular degeneration (AMD), the leading cause of vision loss in the elderly.
The Board also approved funding for seven projects in the Discovery Quest Program. The Quest program promotes the discovery of promising new stem cell-based technologies that will be ready to move to the next level, the translational category, within two years, with an ultimate goal of improving patient care.
Pluripotent stem cell-derived bladder epithelial progenitors for definitive cell replacement therapy of bladder cancer
Small Molecule Proteostasis Regulators to Treat Photoreceptor Diseases
U.C. San Diego
Drug Development for Autism Spectrum Disorder Using Human Patient iPSCs
A screen for drugs to protect against chemotherapy-induced hearing loss, using sensory hair cells derived by direct lineage reprogramming from hiPSCs
University of Southern California
Modulation of the Wnt pathway to restore inner ear function
Regenerative Thymic Tissues as Curative Cell Therapy for Patients with 22q11 Deletion Syndrome
Finally, the Board approved the Agency’s 2019 research budget. Given CIRM’s new partnership with the National Heart, Lung, Blood Institute (NHLBI) to accelerate promising therapies that could help people with Sickle Cell Disease (SCD) the Agency is proposing to set aside $30 million in funding for this program.
Congresswoman Barbara Lee (D-CA 13th District)
Congresswoman Barbara Lee (D-CA 13th DIstrict)
“I am deeply grateful for organizations like CIRM and NHLBI that do vital work every day to help people struggling with Sickle Cell Disease,” said Congresswoman Barbara Lee (D-CA 13th District). “As a member of the House Appropriations Subcommittee on Labor, Health and Human Services, and Education, I know well the importance of this work. This innovative partnership between CIRM and NHLBI is an encouraging sign of progress, and I applaud both organizations for their tireless work to cure Sickle Cell Disease.”
Under the agreement CIRM and the NHLBI will coordinate efforts to identify and co-fund promising therapies targeting SCD. Programs that are ready to start an IND-enabling or clinical trial project for sickle cell can apply to CIRM for funding from both agencies. CIRM will share application information with the NHLBI and CIRM’s Grants Working Group (GWG) – an independent panel of experts which reviews the scientific merits of applications – will review the applications and make recommendations. The NHLBI will then quickly decide if it wants to partner with CIRM on co-funding the project and if the CIRM governing Board approves the project for funding, the two organizations will agree on a cost-sharing partnership for the clinical trial. CIRM will then set the milestones and manage the single CIRM award and all monitoring of the project.
“This is an extraordinary opportunity to create a first-of-its-kind partnership with the NHLBI to accelerate the development of curative cell and gene treatments for patients suffering with Sickle Cell Disease” says Maria T. Millan, MD, President & CEO of CIRM. “This allows us to multiply the impact each dollar has to find relief for children and adults who battle with this life-threatening, disabling condition that results in a dramatically shortened lifespan. We are pleased to be able to leverage CIRM’s acceleration model, expertise and infrastructure to partner with the NHLBI to find a cure for this condition that afflicts 100,000 Americans and millions around the globe.”