California has the largest aging population in the United States. The U.S. Census Bureau has estimated that one in five Californians will be 65 or older by the year 2030. Unfortunately with age comes a wide of health related issues that can arise such as Alzheimer’s.
Alzheimer’s is caused by changes in the brain that affect memory and thinking skills. The disease can progress to the point where carrying out the simplest tasks become quite a challenge. In the United States alone, 5.8 million people are living with Alzheimer’s, 630,000 of whom live in California. By 2050, the number of people with Alzheimer’s in the United States is expected to increase to almost 14 million.
To address this growing problem, California Governor Gavin Newsom announced the creation of a California Alzheimer’s Task Force comprised of scientists, politicians, and other individuals dedicated to addressing the needs of the Alzheimer’s community and the impact the disease has on California. The new task force has been tasked with releasing a report on the disease and ways to address the challenges it poses by 2020.
One of these task force members is our very own Lauren Miller Rogen, who is a dedicated member of our governing Board and the co-founder of Hilarity for Charity, a charity organization that raises awareness about and funds for research into Alzheimer’s. In addition to her advocacy work, Lauren is also a screenwriter and actress, staring alongside her husband Seth Rogen in movies such as 50/50 and Superbad.
“I’m so honored to join the Task Force to fight for the 670,000 Californians currently living with Alzheimer’s and for those who care for them,” Miller Rogen said. “This is a tremendous and diverse group who intend to create and propose real ideas to change the course of this disease.”
For Lauren, her journey towards becoming an advocate for Alzheimer’s is a very personal one. Her grandfather died of Alzheimer’s when she was just 12 years old and her grandmother died of the disease six years after that. Now, her mother is struggling with Alzheimer’s, having been diagnosed at the age of 55.
In ancient Greek mythology, a Chimera was a creature that was usually depicted as a lion with an additional goat head and a serpent for a tail. Due to the Chimera’s animal hybrid nature, the term “chimeric” came to fruition in the scientific community as a way to describe an organism containing two or more different sets of DNA.
A CIRM-funded study conducted by Dr. Mathew Blurton-Jones and his team at UC Irvine describes a way for human brain immune cells, known as microglia, to grow and function inside mice. Since the mice contain a both human cells and their own mice cells, they are described as being chimeric.
In order to develop this chimeric “mighty mouse” model, Dr. Blurton-Jones and his team generated induced pluripotent stem cells (iPSCs), which have the ability to turn into any kind of cell, from cell samples donated by adult patients. For this study, the researchers converted iPSCs into microglia, a type of immune cell found in the brain, and implanted them into genetically modified mice. After a few months, they found that the implanted cells successfully integrated inside the brains of the mice.
By finding a way to look at human microglia grow and function in real time in an animal model, scientists can further analyze crucial mechanisms contributing to neurological conditions such as Alzheimer’s, Parkinson’s, traumatic brain injury, and stroke.
For this particular study, Dr. Blurton-Jones and his team looked at human microglia in the mouse brain in relation to Alzheimer’s, which could hold clues to better understand and treat the disease. The team did this by introducing amyloid plaques, protein fragments in the brain that accumulate in people with Alzheimer’s, and evaluating how the human microglia responded. They found that the human microglia migrated toward the amyloid plaques and surrounding them, which is what is observed in Alzheimer’s patients.
In a press release, Dr. Blurton-Jones expressed the importance of studying microglia by stating that,
“Microglia are now seen as having a crucial role in the development and progression of Alzheimer’s. The functions of our cells are influenced by which genes are turned on or off. Recent research has identified over 40 different genes with links to Alzheimer’s and the majority of these are switched on in microglia. However, so far we’ve only been able to study human microglia at the end stage of Alzheimer’s in post-mortem tissues or in petri dishes.”
Furthermore, Dr. Blurton-Jones highlighted the importance of looking at human microglia in particular by saying that,
“The human microglia also showed significant genetic differences from the rodent version in their response to the plaques, demonstrating how important it is to study the human form of these cell.”
The full results of this study were published in Cell.
Getting a breast cancer diagnosis is devastating news in and of itself. Currently, there are treatment options that target three different types of receptors, which are named hormone epidermal growth factor receptor 2 (HER-2), estrogen receptors (ER), and progesterone receptors (PR), commonly found in breast cancer cells, . Unfortunately, in triple-negative breast cancer, which occurs in 10-20% of breast cancer cases, all three receptors are absent, making this form of breast cancer very aggressive and difficult to treat.
In recent years, researchers have discovered that proteins on the cell surface can tell macrophages, an immune cell designed to detect and engulf foreign or abnormal cells, not to eat and destroy them. This can be useful to help normal cells keep the immune system from attacking them, but cancer cells can also use these “don’t eat me” signals to hide from the immune system.
In fact, because of this concept, a CIRM-funded clinical trial is being conducted that uses an antibody called 5F9 to block a “don’t eat me” signal known as CD47 that is found in cancer cells. The results of this trial, which have been announced in a previous blog post, are very promising.
Further building on this concept, a CIRM-funded study has now discovered a potential new target for triple-negative breast cancer as well as ovarian cancer. Dr. Irv Weissman and a team of researchers at Stanford University have discovered an additional “don’t eat me” signal called CD24 that cancers seem to use to evade detection and destruction by the immune system.
In a press release, Dr. Weissman talks about his work with CD47 and states that,
“Finding that not all patients responded to anti-CD47 antibodies helped fuel our research at Stanford to test whether non-responder cells and patients might have alternative ‘don’t eat me’ signals.”
The scientists began by looking for signals that were produced more highly in cancers than in the tissues from which the cancers arose. It is here that they discovered CD24 and then proceeded to implant human breast cancer cells in mice for testing. When the CD24 signaling was blocked, the mice’s immune system attacked the cancer cells.
An important discovery was that ovarian and triple-negative breast cancer were highly affected by blocking of CD24 signaling. The other interesting discovery was that the effectiveness of CD24 blockage seems to be complementary to CD47 blockage. In other words, some cancers, like blood cancers, seem to be highly susceptible to blocking CD47, but not to CD24 blockage. For other cancers, like ovarian cancer, the opposite is true. This could suggest that most cancers will be susceptible to the immune system by blocking the CD24 or CD47 signal, and that cancers may be even more vulnerable when more than one “don’t eat me” signal is blocked.
Dr. Weissman and his team are now hopeful that potential therapies to block CD24 signaling will follow in the footsteps of the clinical trials related to CD47.
In addition to approving funding for breast cancer related brain metastases last week, the CIRM Board also approved an additional $19.7 million geared towards our translational research program. The goal of this program is to help promising projects complete the testing needed to begin talking to the US Food and Drug Administration (FDA) about holding a clinical trial.
Before getting into the details of each project, here is a table with a brief synopsis of the awards:
TRAN1 – 11532
$3.73 million was awarded to Dr. Mark Humayun at USC to develop a novel therapeutic product capable of slowing the progression of age-related macular degeneration (AMD).
AMD is an eye disease that causes severe vision impairment, resulting in the inability to read, drive, recognize faces, and blindness if left untreated. It is the leading cause of vision loss in the U.S. and currently affects over 2 million Americans. By the year 2050, it is projected that the number of affected individuals will more than double to over 5 million. A layer of cells in the back of the eye called the retinal pigment epithelium (RPE) provide support to photoreceptors (PRs), specialized cells that play an important role in our ability to process images. The dysfunction and/or loss of RPE cells plays a critical role in the loss of PRs and hence the vision problems observed in AMD. One form of AMD is known as dry AMD (dAMD) and accounts for about 90% of all AMD cases.
The approach that Dr. Humayun is developing will use a biologic product produced by human embryonic stem cells (hESCs). This material will be injected into the eye of patients with early development of dAMD, supporting the survival of photoreceptors in the affected retina.
TRAN1 – 11579
$6.23 million was awarded to Dr. Mark Tuszynski at UCSD to develop a neural stem cell therapy for spinal cord injury (SCI).
According to data from the National Spinal
Cord Injury Statistical Center, as of 2018, SCI affects an estimated 288,000
people in the United States alone, with about 17,700 new cases each year. There
are currently no effective therapies for SCI. Many people suffer SCI in early
adulthood, leading to life-long disability and suffering, extensive treatment
needs and extremely high lifetime costs of health care.
The approach that Dr. Tuszynski is developing will use hESCs to create neural stem cells (NSCs). These newly created NSCs would then be grafted at the site of injury of those with SCI. In preclinical studies, the NSCs have been shown to support the formation of neuronal relays at the site of SCI. The neuronal relays allow the sensory neurons in the brain to communicate with the motor neurons in the spinal cord to re-establish muscle control and movement.
TRAN1 – 11548
$4.83 million was awarded to Dr. Brian Cummings at UC Irvine to develop a neural stem cell therapy for traumatic brain injury (TBI).
TBI is caused by a bump, blow, or jolt to the head that disrupts the normal function of the brain, resulting in emotional, mental, movement, and memory problems. There are 1.7 million people in the United States experiencing a TBI that leads to hospitalization each year. Since there are no effective treatments, TBI is one of the most critical unmet medical needs based on the total number of those affected and on a cost basis.
The approach that Dr. Cummings is developing will also use hESCs to create NSCs. These newly created NSCs would be integrated with injured tissue in patients and have the ability to turn into the three main cell types in the brain; neurons, astrocytes, and oligodendrocytes. This would allow for TBI patients to potentially see improvements in issues related to memory, movement, and anxiety, increasing independence and lessening patient care needs.
TRAN1 – 11628
$4.96 million was awarded to Dr. Evan Snyder at Sanford Burnham Prebys to develop a neural stem cell therapy for perinatal hypoxic-ischemic brain injury (HII).
HII occurs when there is a lack of oxygen flow to the brain. A newborn infant’s body can compensate for brief periods of depleted oxygen, but if this lasts too long, brain tissue is destroyed, which can cause many issues such as developmental delay and motor impairment. Current treatment for this condition is whole-body hypothermia (HT), which consists of significantly reducing body temperature to interrupt brain injury. However, this is not very effective in severe cases of HII.
The approach that Dr. Snyder is developing will use an established neural stem cell (NSC) line. These NSCs would be injected and potentially used alongside HT treatment to increase protection from brain injury.
Yesterday the governing Board of the California Institute for Regenerative Medicine (CIRM) awarded $9.28 million to Dr. Saul Priceman at City of Hope to conduct a clinical trial for the treatment of breast cancer related brain metastases, which are tumors in the brain that have spread from the original site of the breast cancer.
This award brings the total number of CIRM-funded clinical trials to 56.
Breast cancer is the second-most common cancer in women, both in the United States (US) and worldwide. It is estimated that over 260,000 women in the US will be diagnosed with breast cancer in 2019 and 1 out of 8 women in the US will get breast cancer at some point during her lifetime. Some types of breast cancer have a high likelihood of metastasizing to the brain. When that happens, there are few treatment options, leading to a poor prognosis and poor quality of life.
Dr. Priceman’s clinical trial is testing a therapy to treat brain metastases that came from breast cancers expressing high levels of a protein called HER2. The therapy consists of a genetically-modified version of the patient’s own T cells, which are an immune system cell that can destroy foreign or abnormal cells. The T cells are modified with a protein called a chimeric antigen receptor (CAR) that recognizes the tumor protein HER2. These modified T cells (CAR-T cells) are then infused into the patient’s brain where they are expected to detect and destroy the HER2-expressing tumors in the brain.
CIRM has also funded the earlier work related to this study, which was critical in preparing the therapy for Food and Drug Administration (FDA) approval for permission to start a clinical trial in people.
“When a patient is told that their cancer has metastasized to other areas of the body, it can be devastating news,” says Maria T. Millan, M.D., the President and CEO of CIRM. “There are few options for patients with breast cancer brain metastases. Standard of care treatments, which include brain irradiation and chemotherapy, have associated neurotoxicity and do little to improve survival, which is typically no more than a few months. CAR-T cell therapy is an exciting and promising approach that now offers us a more targeted approach to address this condition.”
The CIRM Board also approved investing $19.7 million in four awards in the Translational Research program. The goal of this program is to help promising projects complete the testing needed to begin talking to the US Food and Drug Administration (FDA) about holding a clinical trial.
Dr. Mark Tuszynski at the University of California San Diego (UCSD) was awarded $6.23 million to develop a therapy for spinal cord injury (SCI). Dr. Tuszynski will use human embryonic stem cells (hESCs) to create neural stem cells (NSCs) which will then be grafted at the injury site. In preclinical studies, the NSCs have been shown to help create a kind of relay at the injury site, restoring communication between the brain and spinal cord and re-establishing muscle control and movement.
Dr. Mark Humayun at the University of Southern California (USC) was awarded $3.73 million to develop a novel therapeutic product capable of slowing the progression of age-related macular degeneration (AMD), the leading cause of vision loss in the US.
The approach that Dr. Humayun is developing will use a biologic product produced by human embryonic stem cells (hESCs). This material will be injected into the eye of patients with early development of dry AMD, supporting the survival of photoreceptors in the affected retina, the kind of cells damaged by the disease.
The TRAN1 awards went to:
Stay tuned for our next blog which will dive into each of these awards in much more detail.
A sense of balance is important for a wide range of activities, from simple ones such as walking, running, and driving, to more intricate ones such as dancing, rock climbing, and tight-rope walking. A lack of physical balance in the body can lead to an inbalance in trying to live a normal everyday life.
One primary cause of balance disorders is a problem with hair cells located inside the inner ear, which play a role in maintaining balance, spatial orientation, and regulating eye movement. Damage to these cells can occur as a result from infections, genetic disorders, or aging. Unfortunately, in humans, hair cells in the inner ear regenerate on their own very minimally. In the United States alone, 69 million people experience balance disorders. Symptoms of this disorder include a “spinning” feeling, lack of balance, nausea, and difficulty tracking objects using the eyes.
However, a CIRM funded study has showed promising results for helping treat this disorder. Researchers at Stanford University have discovered a way to regenerate hair cells in the inner ear of mice, giving them a better sense of balance. To do this, the researchers impaired the hair cells in the inner ear of mice and measured how well they regenerated on their own to obtain a baseline measurement. They found that about a third of the cells regenerated on their own.
Next, the researchers manipulated Atoh1, a transcription factor that regulates hair cell formation in mice. By overexpressing Atoh1, the researchers found that as much as 70% of hair cells regenerated in the mice. Additionally, 70% of these mice also recovered their sense of balance. This simple proof of concept could potentially be applied in humans to treat similar disorders related to the loss of hair cells in the inner ear.
In a press release, Dr. Alan Cheng, senior author of this study, is quoted as saying,
“This is very exciting. It’s an important first step to find treatment for vestibular disorders. We couldn’t get sufficient regeneration to recover function before.”
It’s never easy to tell someone that they are too late, that they missed the deadline. It’s particularly hard when you know that the person you are telling that to has spent years working on a project and now needs money to take it to the next level. But in science, as in life, it’s always better to tell people what they need to know rather than what they would like to hear.
And so, we have posted
a notice on our website for researchers thinking about applying for funding
that, except in a very few cases, they are too late, that there is no money
available for new projects, whether it’s Discovery, Translational or Clinical.
Here’s that notice:
that the budget allocation of funds for new awards under the CIRM clinical
program (CLIN1, CLIN2 and CLIN3) may be depleted within the next two to three
months. CIRM will accept applications for the monthly deadline on June 28, 2019
but will suspend application submissions after that date until further notice.
All applicants should note that the review of submitted applications may be
halted at any point in the process if funds are depleted prior to completion of
the 3-month review cycle. CIRM will notify applicants of such an occurrence.
Therefore, submission and acceptance of an application to CIRM does not
guarantee the availability of funds or completion of a review cycle.
of applications for the CIRM/NHLBI Cure Sickle Cell Initiative (CLIN1 SCD,
CLIN2 SCD) are unaffected and application submissions for this program will
We do, of course, have enough money set aside to continue
funding all the projects our Board has already approved, but we don’t have
money for new projects (except for some sickle cell disease projects).
In truth our funding has lasted a lot longer than anyone
anticipated. When Proposition 71 was approved the plan was to give CIRM $300
million a year for ten years. That was back in 2004. So what happened?
Well, in the early years stem cell science was still very
much in its infancy with most of the work being done at a basic or Discovery
level. Those typically don’t require very large sums so we were able to fund
many projects without hitting our $300m target. As the field progressed,
however, more and more projects were at the clinical trial stage and those need
multiple millions of dollars to be completed. So, the money went out faster.
To date we have funded 55 clinical trials and our
early support has helped more than a dozen other projects get into clinical
trials. This includes everything from cancer and stroke, to vision loss and
diabetes. It’s a good start, but we feel there is so much more to do.
Followers of news about CIRM know there is talk about a possible ballot initiative next year that would provide another $5.5 billion in funding for us to help complete the mission we have started.
Over the years we have built a pipeline of promising
projects and without continued support many of those projects face a difficult
future. Funding at the federal level is under threat and without CIRM there
will be a limited number of funding alternatives for them to turn to.
Telling researchers we don’t have any money to support their
work is hard. Telling patients we don’t have any money to support work that
could lead to new treatments for them, that’s hardest of all.
At first glance, a scientific conference is not the place you would think about going to learn about how to run a political or any other kind of campaign. But then the ISSCR Annual Meeting is not your average conference. And that’s why CIRM is there and has been going to these events for as long as we have been around.
For those who don’t know, ISSCR is the International Society
for Stem Cell Research. It’s the global industry representative for the field
of stem cell research. It’s where all the leading figures in the field get
together every year to chart the progress in research.
But it’s more than just the science that gets discussed. One of the panels kicking off this year’s conference was on ‘Why is it Important to Communicate with Policy Makers, the Media and the Public?” It was a wide-ranging discussion on the importance of learning the best ways for the scientific community to explain what it is they do, why they do it, and why people should care.
Morrison, a former President of ISSCR, talked about his experience
trying to pass a bill in Michigan that would enable scientists to do embryonic
stem cell research. At the time CIRM was spending millions of dollars funding
scientists in California to create new lines of embryonic stem cells; in
Michigan anyone doing the same could be sent to prison for a year. He said the
opposition ran a fear-based campaign, lying about the impact the bill would
have, that it would enable scientists to create half man-half cow creatures
(no, really) or human clones. Learning to counter those without descending to
their level was challenging, but ultimately Morrison was successful in
overcoming opposition and getting the bill passed.
Temple, of the Neural Stem Cell Institute, talked about testifying
to a Congressional committee about the importance of fetal tissue research and
faced a barrage of hostile questions that misrepresented the science and
distorted her views. In contrast Republicans on the committee had invited a group
that opposed all fetal tissue research and fed them a bunch of softball
questions; the answers the group gave not only had no scientific validity, they
were just plain wrong. Fortunately, Temple says she had done a lot of
preparation (including watching two hours Congressional hearings on C-SPAN to understand how these hearings
worked) and had her answers ready. Even so she said one of the big lessons she
stressed is the need to listen to what others are saying and respond in ways
that address their fears and don’t just dismiss them.
Other presenters talked about their struggles with different
issues and different audiences but similar experiences; how do you communicate
clearly and effectively. The answer is actually pretty simple. You talk to
people in a way they understand with language they understand. Not with dense
scientific jargon. Not with reams of data. Just by telling simple stories that
illustrate what you did and who it helped or might help.
The power of ISSCR is that it can bring together a roomful
of brilliant scientists from all over the world who want to learn about these
things, who want to be better communicators. They know that much of the money
for scientific research comes from governments or state agencies, that this is
public money, and that if the public is going to continue to support this
research it needs to know how that money is being spent.
That’s a message CIRM has been promoting for years. We know
that communicating with the public is not an option, it’s a responsibility.
That’s why, at a time when the very notion of science sometimes seems to be
under attack, and the idea of public funding for that science is certainly
under threat, having meetings like this that brings researchers together and
gives them access to new tools is vital. The tools they can “get” at ISSCR are
ones they might never learn in the lab, but they are tools that might just mean
they get the money needed to do the work they want to.
Today the governing Board of the California Institute for
Regenerative Medicine (CIRM) approved a grant of almost $12 million to Dr.
Stephanie Cherqui at the University of California, San Diego (UCSD) to conduct
a clinical trial for treatment of cystinosis.
award brings the total number of CIRM funded clinical trials to 55.
a rare disease that primarily affects children and young adults, and leads to
premature death, usually in early adulthood. Patients inherit
defective copies of a gene called CTNS, which results in abnormal accumulation
of an amino acid called cystine in all cells of the body. This buildup of cystine can lead to
multi-organ failure, with some of earliest and most pronounced effects on the
kidneys, eyes, thyroid, muscle, and pancreas.
Many patients suffer end-stage kidney failure and severe vision defects
in childhood, and as they get older, they are at increased risk for heart
disease, diabetes, bone defects, and neuromuscular defects. There is currently a drug treatment for
cystinosis, but it only delays the progression of the disease, has severe side
effects and is expensive.
Dr. Cherqui’s clinical trial will use a gene therapy
approach to modify a patient’s own blood stem cells with a functional version
of the defective CTNS gene. Based on pre-clinical
data, the approach is to reintroduce the corrected stem cells into the patient
to give rise to blood cells that will reduce cystine buildup in affected
Because this is the first time this approach has been tested in patients, the primary goal of the clinical trial is to see if the treatment is safe. In addition, patients will be monitored for improvements in the symptoms of their disease. This award is in collaboration with the University of California, Los Angeles which will handle the manufacturing of the therapy.
CIRM has also funded the preclinical work
for this study, which involved completing the testing needed to apply to the
Food and Drug Administration (FDA) for permission to start a clinical trial in
“CIRM has funded 24 clinical stage programs utilizing
cell and gene medicine approaches to date,” says Maria T. Millan, M.D., the
President and CEO of CIRM. “This project
continues to broaden the scope of unmet medical need we can impact with these
types of approaches.”
From even before we were created by the passage of Proposition 71 back in 2004, the voices of patients and patient advocates have been at the heart of CIRM’s existence. Today they are every bit as vital to the work we do, and even more essential if we are to be able to continue doing that work.
In 2004, the patient advocate community recognized that the research we fund could help them or a loved one battling a deadly disease or disorder. And over the last 15 years that’s exactly what we have done, trying to live up to our mission of accelerating stem cell treatments to patients with unmet medical needs. And with 54 clinical trials already under our belt we have made a good start.
But it’s just a start. We still have a lot to do. The problem is we are quickly running out of money. We expect to have enough money to fund new projects up to the end of this year. After that many great new ideas and promising projects won’t be able to apply to us for support. Some may get funding from other sources, but many won’t. We don’t want to let that happen.
That’s why we are holding a Patient Advocate event next Tuesday, June 25th from 6-7pm in Petree Hall C., at the Los Angeles Convention Center at 1201 South Figueroa Street, LA 90015.
The event is open to everyone and it’s FREE. We have created an Eventbrite page where you can get all the details and RSVP if you are coming. And if you want to get there a little early that’s fine too, we’ll be there from 5pm onwards so you’ll have a chance to ask us any questions you might have beforehand.
It’s going to be an opportunity to learn about the real progress being made in stem cell research, thanks in no small part to CIRM’s funding. We’ll hear from the researchers who are saving lives and changing lives, and from the family of one baby alive today because of that work.
We will hear about the challenges facing CIRM and the field, but also about a possible new ballot initiative for next year that could help re-fund CIRM, giving us the opportunity to continue our work.
That’s where you, the patients and patient advocates and members of the public come in. Without you we wouldn’t be here. Without you we will disappear. Without us the field of stem cell research loses a vital source of support and funding, and potentially-life saving therapies fall by the wayside.
We all have a huge stake in this. So we hope to see you next Tuesday, at the start of what may be the next chapter in the life of CIRM.