Gladstone scientists Deepak Srivastava (left), Yvanka De Soysa (center), and Casey Gifford (right) publish a complete catalog of the cells involved in heart development.
The invention of GPS navigation systems has made finding your way around so much easier, providing simple instructions on how to get from point A to point B. Now, a new study shows that our bodies have their own internal navigation system that helps stem cells know where to go, and when, in order to build a human heart. And the study also shows what can go wrong when even a few cells fail to follow directions.
In this CIRM-supported study, a team of researchers at the Gladstone Institutes in San Francisco, used a new technique called single cell RNA sequencing to study what happens in a developing heart. Single cell RNA sequencing basically takes a snapshot photo of all the gene activity in a single cell at one precise moment. Using this the researchers were able to follow the activity of tens of thousands of cells as a human heart was being formed.
In a story in Science and Research Technology News,
Casey Gifford, a senior author on the study, said this approach helps pinpoint
genetic variants that might be causing problems.
“This sequencing technique allowed us
to see all the different types of cells present at various stages of heart development
and helped us identify which genes are activated and suppressed along the way. We
were not only able to uncover the existence of unknown cell types, but we also
gained a better understanding of the function and behavior of individual
cells—information we could never access before.”
Then they partnered with a team at Luxembourg Centre for Systems
Biomedicine (LCSB) of the University of Luxembourg which ran a
computational analysis to identify which genes were involved in creating
different cell types. This highlighted one specific gene, called Hand2, that controls
the activity of thousands of other genes. They found that a lack of Hand2 in
mice led to an inability to form one of the heart’s chambers, which in turn led
to impaired blood flow to the lungs. The embryo was creating the cells needed
to form the chamber, but not a critical pathway that would allow those cells to
get where they were needed when they were needed.
Gifford says this has given us a deeper insight into how
cells are formed, knowledge we didn’t have before.
“Single-cell technologies can inform us about how organs
form in ways we couldn’t understand before and can provide the underlying cause
of disease associated with genetic variations. We revealed subtle differences
in very, very small subsets of cells that actually have catastrophic
consequences and could easily have been overlooked in the past. This is the
first step toward devising new therapies.”
These therapies are needed to help treat congenital heart
defects, which are the most common and deadly birth defects. There are more
than 2.5 million Americans with these defects. Deepak Srivastava, President of
Gladstone and the leader of the study, said the knowledge gained in this study
could help developed strategies to help address that.
“We’re beginning
to see the long-term consequences in adults, and right now, we don’t really
have any way to treat them. My hope is that if we can understand the genetic
causes and the cell types affected, we could potentially intervene soon after
birth to prevent the worsening of their state over time.
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
Illustration of a healthy eye vs eye with AMD
$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
Illustration depicting the role neuronal relays play in muscle sensation
$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
Graphic depicting the challenges of traumatic brain injury (TBI)
$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
Illustration depicting the brain damage that occurs under hypoxic-ischemic conditions
$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.
Fragile X syndrome (FXS) is a genetic disorder that is the most common form of inherited intellectual disability in children, and has also been linked to a form of autism. Uncovering the cause of FXS could help lead to a deeper understanding of autism, what causes it and ultimately, it’s hoped, to treating or even preventing it.
Researchers at Children’s Hospital in Chicago looked at FXS at the stem cell level and found how a genetic defect has an impact on the development of neurons (nerve cells in the brain) and how that in turn has an impact on the developing brain in the fetus.
In a news release on Eurekalert, Dr. Yongchao Ma, the senior author of the study, says this identified a problem at a critical point in the development of the brain:
“During embryonic brain development,
the right neurons have to be produced at the right time and in the right
numbers. We focused on what happens in the stem cells that leads to slower
production of neurons that are responsible for brain functions including learning
and memory. Our discoveries shed light on the earliest stages of disease
development and offer novel targets for potential treatments.”
The team looked at neural stem cells and found that a lack
of one protein, called FMRP, created a kind of cascade that impacted the
ability of the cells to turn into neurons. Fewer neurons meant impaired brain
development.
The findings, published in the journal Cell Reports, help explain how
genetic information flows in cells in developing babies and, according to Dr.
Ma, could lead to new ideas on how to treat problems.
“Currently we are exploring how to
stimulate FMRP protein activity in the stem cell, in order to correct the
timing of neuron production and ensure that the correct amount and types of
neurons are available to the developing brain. There may be potential for gene
therapy for fragile X syndrome.”
Joseph Wu is co-senior author of a study that demonstrates how patient-derived heart cells can help scientists better study the heart and screen potential therapies. Photo courtesy of Steve Fisch
Heart disease continues to be the number one cause of death in the United States. An estimated 375,000 people have a genetic form of heart disease known as familial dilated cardiomyopathy. This occurs when the heart muscle becomes weakened in one chamber in the heart, causing the open area of the chamber to become enlarged or dilated. As a result of this, the heart can no longer beat regularly, causing shortness of breath, chest pain and, in severe cases, sudden and deadly cardiac arrest.
A diagram of a normal heart compared to one with the dilated cardiomyopathy
A CIRM funded study by a team of researchers at Stanford University looked further into this form of genetic heart disease by taking a patient’s skin cells and converting them into stem cells known as induced pluripotent stem cells (iPSCs), which can become any type of cell in the body. These iPSCs were then converted into heart muscle cells that pulse just as they do in the body. These newly made heart muscle cells beat irregularly, similar to what is observed in the genetic heart condition.
Upon further analysis, the researchers linked a receptor called PGDF to cause various genes to be more highly activated in the mutated heart cells compared to normal ones. Two drugs, crenolanib and sunitinib, interfere with the PGDF receptor. After treating the abnormal heart cells, they began beating more regularly, and their gene-activation patterns more closely matched those of cells from healthy donors.
These two drugs are already FDA-approved for treating various cancers, but previous work shows that the drugs may damage the heart at high doses. The next step would be determining the right dose of the drug. The current study is part of a broader effort by the researchers to use these patient-derived cells-in-a-dish to screen for and discover new drugs.
Dr. Joseph Wu, co-senior author of this study, and his team have generated heart muscle cells from over 1,000 patients, including those of Dr. Wu, his son, and his daughter. In addition to using skin cells, the same technique to create heart cells from patients can also be done with 10 milliliters of blood — roughly two teaspoons.
“With 10 milliliters of blood, we can make clinically usable amounts of your beating heart cells in a dish…Our postdocs have taken my blood and differentiated my pluripotent stem cells into my brain cells, heart cells and liver cells. I’m asking them to test some of the medications that I might need to take in the future.”
The full results of this study were published in Nature.
At CIRM we are privileged to work with many remarkable people who combine brilliance, compassion and commitment to their search for new therapies to help people in need. One of those who certainly fits that description is UC Davis’ Jan Nolta.
This week the UC Davis Newsroom posted a great interview with Jan. Rather than try and summarize what she says I thought it would be better to let her talk for herself.
Jan Nolta
Talking research, unscrupulous clinics, and sustaining the momentum
(SACRAMENTO) —
In 2007, Jan Nolta
returned to Northern California from St. Louis to lead what was at the
time UC Davis’ brand-new stem cell program. As director of the UC Davis Stem Cell Program
and the Institute for Regenerative Cures, she has overseen the opening
of the institute, more than $140 million in research grants, and dozens
upon dozens of research studies. She recently sat down to answer some
questions about regenerative medicine and all the work taking place at UC Davis Health.
Q: Turning stem cells into cures has been your mission and mantra since you founded the program. Can you give us some examples of the most promising research?
I am so excited about our research. We have about 20 different disease-focused teams.
That includes physicians, nurses, health care staff, researchers and
faculty members, all working to go from the laboratory bench to
patient’s bedside with therapies.
Perhaps the most promising and
exciting research right now comes from combining blood-forming
stem cells with gene therapy. We’re working in about
eight areas right now, and the first cure, something that we definitely
can call a stem cell “cure,” is coming from this combined approach.
Soon,
doctors will be able to prescribe this type of stem cell therapy.
Patients will use their own bone marrow or umbilical cord stem cells.
Teams such as ours, working in good manufacturing practice
facilities, will make vectors, essentially “biological delivery
vehicles,” carrying a good copy of the broken gene. They will be
reinserted into a patient’s cells and then infused back into the
patient, much like a bone marrow transplant.
“Perhaps the most promising and exciting research right now comes from combining blood-forming stem cells with gene therapy.”
Along with treating the famous bubble baby disease,
where I had started my career, this approach looks very promising for
sickle cell anemia. We’re hoping to use it to treat several different
inherited metabolic diseases. These are conditions characterized by an
abnormal build-up of toxic materials in the body’s cells. They interfere
with organ and brain function. It’s caused by just a single enzyme.
Using the combined stem cell gene therapy, we can effectively put a good
copy of the gene for that enzyme back into a patient’s bone marrow stem
cells. Then we do a bone marrow transplantation and bring back a
person’s normal functioning cells.
The beauty of this therapy is
that it can work for the lifetime of a patient. All of the blood cells
circulating in a person’s system would be repaired. It’s the number one
stem cell cure happening right now. Plus, it’s a therapy that won’t be
rejected. These are a patient’s own stem cells. It is just one type of
stem cell, and the first that’s being commercialized to change cells
throughout the body.
Q: Let’s step back for a moment. In 2004, voters approved Proposition 71.
It has funded a majority of the stem cell research here at UC Davis and
throughout California. What’s been the impact of that ballot measure
and how is it benefiting patients?
We have learned so
much about different types of stem cells, and which stem cell will be
most appropriate to treat each type of disease. That’s huge. We had to
first do that before being able to start actual stem cell therapies. CIRM [California Institute for Regenerative Medicine] has funded Alpha Stem Cell Clinics.
We have one of them here at UC Davis and there are only five in the
entire state. These are clinics where the patients can go for
high-quality clinical stem cell trials approved by the FDA
[U.S. Food and Drug Administration]. They don’t need to go to
“unapproved clinics” and spend a lot of money. And they actually
shouldn’t.
“By the end of this year, we’ll have 50 clinical trials.”
By the end of this year, we’ll have 50 clinical trials [here at UC Davis Health]. There are that many in the works.
Our Alpha Clinic
is right next to the hospital. It’s where we’ll be delivering a lot of
the immunotherapies, gene therapies and other treatments. In fact, I
might even get to personally deliver stem cells to the operating room
for a patient. It will be for a clinical trial involving people who have
broken their hip. It’s exciting because it feels full circle, from
working in the laboratory to bringing stem cells right to the patient’s
bedside.
We have ongoing clinical trials
for critical limb ischemia, leukemia and, as I mentioned, sickle cell
disease. Our disease teams are conducting stem cell clinical trials
targeting sarcoma, cellular carcinoma, and treatments for dysphasia [a
swallowing disorder], retinopathy [eye condition], Duchenne muscular
dystrophy and HIV. It’s all in the works here at UC Davis Health.
There’s
also great potential for therapies to help with renal disease and
kidney transplants. The latter is really exciting because it’s like a
mini bone marrow transplant. A kidney recipient would also get some
blood-forming stem cells from the kidney donor so that they can better
accept the organ and not reject it. It’s a type of stem cell therapy
that could help address the burden of being on a lifelong regime of
immunosuppressant drugs after transplantation.
Q: You and
your colleagues get calls from family members and patients all the
time. They frequently ask about stem cell “miracle” cures. What should
people know about unproven treatments and unregulated stem cell clinics?
That’s a great question.The number one rule is that if
you’re asked to pay money for a stem cell treatment, don’t do it. It’s a
big red flag.
When it comes to advertised therapies: “The number one rule is that if you’re asked to pay money for a stem cell treatment, don’t do it. It’s a big red flag.”
Unfortunately,
there are unscrupulous people out there in “unapproved clinics” who
prey on desperate people. What they are delivering are probably not even
stem cells. They might inject you with your own fat cells, which
contain very few stem cells. Or they might use treatments that are not
matched to the patient and will be immediately rejected. That’s
dangerous. The FDA is shutting these unregulated clinics down one at a
time. But it’s like “whack-a-mole”: shut one down and another one pops
right up.
On the other hand, the Alpha Clinic is part of our
mission is to help the public get to the right therapy, treatment or
clinical trial. The big difference between those who make patients pay
huge sums of money for unregulated and unproven treatments and UC Davis
is that we’re actually using stem cells. We produce them in rigorously
regulated cleanroom facilities. They are certified to contain at least 99% stem cells.
Patients
and family members can always call us here. We can refer them to a
genuine and approved clinical trial. If you don’t get stem cells at the
beginning [of the clinical trial] because you’re part of the placebo
group, you can get them later. So it’s not risky. The placebo is just
saline. I know people are very, very desperate. But there are no miracle
cures…yet. Clinical trials, approved by the FDA, are the only way we’re
going to develop effective treatments and cures.
Q:
Scientific breakthroughs take a lot of patience and time. How do you and
your colleagues measure progress and stay motivated?
Motivation? “It’s all for the patients.”
It’s
all for the patients. There are not good therapies yet for many
disorders. But we’re developing them. Every day brings a triumph.
Measuring progress means treating a patient in a clinical trial, or
developing something in the laboratory, or getting FDA approval. The big
one will be getting biological license approval from the FDA, which
means a doctor can prescribe a stem cell or gene therapy treatment. Then
it can be covered by a patient’s health insurance.
I’m a cancer
survivor myself, and I’m also a heart patient. Our amazing team here at
UC Davis has kept me alive and in great health. So I understand it from
both sides. I understand the desperation of “Where do I go?” and “What
do I do right now?” questions. I also understand the science side of
things. Progress can feel very, very slow. But everything we do here at
the Institute for Regenerative Cures is done with patients in mind, and
safety.
We know that each day is so important when you’re watching
a loved one suffer. We attend patient events and are part of things
like Facebook groups, where people really pour their hearts out. We say
to ourselves, “Okay, we must work harder and faster.” That’s our
motivation: It’s all the patients and families that we’re going to help
who keep us working hard.
Medical treatments for a variety of diseases have advanced dramatically in recent decades, but sometimes they come with a cost; namely damage to surrounding tissues and organs. That’s where stem cell research and regenerative medicine come in. Those fields seek to develop new ways of repairing the damage. But how do you see if those repairs are working? Researchers at Purdue say they have found a way to do just that.
The researchers have developed a 3D technology that allows
them to track, map and monitor what happens with cells and tissues that are
being used to repair damage caused by disease or the treatment for the disease.
By observing the cells and tissues they can see if they are staying where they
are needed and if they are working.
The technology, published in the journalACS Nano, uses tiny sensors placed on a flexible scaffold to monitor the new materials in the body. Ingeniously the scaffold is buoyant, so it can float and survive in the wet conditions found in many parts of the body.
In a news
release, Chi Hwan Lee, the leader of the research team, says the device could
help millions of people:
“Tissue
engineering already provides new hope for hard-to-treat disorders, and our
technology brings even more possibilities. This device offers an expanded set
of potential options to monitor cell and tissue function after surgical transplants
in diseased or damaged bodies. Our technology offers diverse options for
sensing and works in moist internal body environments that are typically
unfavorable for electronic instruments.”
Purdue created this video showing the device and explaining how it works.
Alan Cheng and his colleagues were able to regenerate hair cells inside the ears of mice — a first in mature mammals. Photo Courtesy of Steve Fisch
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.”
The complete results of this study were published in Cell Reports.
There’s a wonderful moment at the end of the movie The Candidate (starring Robert Redford, 87% approval on Rotten Tomatoes!) about a modern political campaign for a US Senate seat. Redford (spoiler alert) plays a come-from-behind candidate and at the end when he wins he turns to his campaign manager and says “Now what?”.
I think that’s how a lot of people associated with Proposition
71 felt when it was approved by California voters in 2004, creating CIRM. Now
what? During the campaign you are so focused on crossing the finish line that when
the campaign is over you have to pause because you just realized it wasn’t the
finishing line, it was actually the starting line.
For us “now what” involved hiring a staff, creating
oversight groups of scientists and ethics experts, developing strategies and
then mechanisms for funding, and then mechanisms for tracking that funding to
make sure it was being used properly. It was creating something from scratch
and trying to do something that no state agency had done before.
Fifteen years later we are coming to the end of the funding
provided by Prop 71 and that question keeps popping up again, “Now what?” And
that’s what we are going to be talking about in our next Facebook Live.
We have three great experts on our panel. They are scientists
and researchers and leaders in biotech, but also members of our CIRM Board. We
rely on their experience and expertise in making key decisions and you can rely
on them to pull back the curtain and talk about the things that matter most to
them in helping advance our mission, and in helping secure our legacy.
Anne-Marie
Duliege MD, has more than 25 years of experience in the medical world, starting
out as a pediatrician and then moving into research. She has experience
developing new therapies for auto-immune disorders, lung problems and
infectious diseases.
Like Anne-Marie, Joe Panetta, has years of experience working in the research field, and is currently President & CEO of Biocom, the California association that advocates for more than 1,200 companies, universities and research institutes working in biotechnology.
Finally, Dave Martin
MD, came to CIRM after stints at the National Institutes of Health (NIH),
UC San Francisco, Genentech, Chiron and several other highly-regarded
organizations. He is also the co-founder, chairman and CEO of
AvidBiotics, a privately held biotechnology company in South San Francisco.
Each brings a different perspective to the work that we do
at CIRM, and each enriches it not just with their intelligence and experience,
but also with their compassion for the patients and commitment to our mission.
When cancer spreads to the bone the results can be devastating
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.
Weian Zhao; photo courtesy UC Irvine
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.”
The research,
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.
The Stem Cellar 