3D brain model shows potential for treatment of hypoxic brain injuries in infants

Image of 3D brain cultures in the Sergiu Pasca lab.
Photo courtesy of Timothy Archibald.

A baby’s time in the womb is one of the most crucial periods in terms of its development. The average length of gestation, which is defined as the amount of time in the womb from conception to birth, is approximately 40 weeks. Unfortunately, for reasons not yet fully understood, there are times that babies are born prematurely, which can lead to problems.

These infants can have underdeveloped portions of the brain, such as the cerebral cortex, which is responsible for advanced brain functions, including cognition, speech, and the processing of sensory and motor information. The brains of premature infants can be so underdeveloped that they are unable to control breathing. This, in combination with underdeveloped lungs, can lower oxygen levels in the blood, which can lead to hypoxic, or low oxygen related, brain injuries.

In a previous study, doctors Anca and Sergiu Pasca and their colleagues at Stanford developed a technique to create a 3D brain that mimics structural and functional aspects of the developing human brain.

Using this same technique, in a new study with the aid of CIRM funding, the team grew a 3D brain that contained cells and genes similar to the human brain midway through the gestational period. They then exposed this 3D brain to low oxygen levels for 48 hours, restored the oxygen level after this time period, and observed any changes.

It was found that progenitor cells in a region known as the subventricular zone, a region that is critical in the growth of the human cortex, are affected. Progenitor cells are “stem cell like” cells that give rise to mature brain cells such as neurons. They also found that the progenitor cells transitioned from “growth” mode to “survival” mode, causing them to turn into neurons sooner than normal, which leads to fewer neurons in the brain and underdevelopment.

In a press release, Dr. Anca Pasca is quoted as saying,

“In the past 20 years, we’ve made a lot of progress in keeping extremely premature babies alive, but 70% to 80% of them have poor neurodevelopmental outcomes.”

The team then tested a small molecule to see if it could potentially reverse this response to low oxygen levels by keeping the progenitor cells in “growth” mode. The results of this are promising and Dr. Sergiu Pasca is quoted as saying,

“It’s exciting because our findings tell us that pharmacologically manipulating this pathway could interfere with hypoxic injury to the brain, and potentially help with preventing damage.”

The complete findings of this study were published in Nature.

Advancing stem cell research in many ways

Speakers at the Alpha Stem Cell Clinics Network Symposium: Photo by Marco Sanchez

From Day One CIRM’s goal has been to advance stem cell research in California. We don’t do that just by funding the most promising research -though the 51 clinical trials we have funded to date clearly shows we do that rather well – but also by trying to bring the best minds in the field together to overcome problems.

Over the years we have held conferences, workshops and symposiums on everything from Parkinson’s disease, cerebral palsy and tissue engineering. Each one attracted the key players and stakeholders in the field, brainstorming ideas to get past obstacles and to explore new ways of developing therapies. It’s an attempt to get scientists, who would normally be rivals or competitors, to collaborate and partner together in finding the best way forward.

It’s not easy to do, and the results are not always obvious right away, but it is essential if we hope to live up to our mission of accelerating stem cell therapies to patients with unmet medical needs.

For example. This past week we helped organize two big events and were participants in another.

The first event we pulled together, in partnership with Cedars-Sinai Medical Center, was a workshop called “Brainstorm Neurodegeneration”. It brought together leaders in stem cell research, genomics, big data, patient advocacy and the Food and Drug Administration (FDA) to tackle some of the issues that have hampered progress in finding treatments for things like Parkinson’s, Alzheimer’s, ALS and Huntington’s disease.

We rather ambitiously subtitled the workshop “a cutting-edge meeting to disrupt the field” and while the two days of discussions didn’t resolve all the problems facing us it did produce some fascinating ideas and some tantalizing glimpses at ways to advance the field.

Alpha Stem Cell Clinics Network Symposium: Photo by Marco Sanchez

Two days later we partnered with UC San Francisco to host the Fourth Annual CIRM Alpha Stem Cell Clinics Network Symposium. This brought together the scientists who develop therapies, the doctors and nurses who deliver them, and the patients who are in need of them. The theme was “The Past, Present & Future of Regenerative Medicine” and included both a look at the initial discoveries in gene therapy that led us to where we are now as well as a look to the future when cellular therapies, we believe, will become a routine option for patients. 

Bringing these different groups together is important for us. We feel each has a key role to play in moving these projects and out of the lab and into clinical trials and that it is only by working together that they can succeed in producing the treatments and cures patients so desperately need.

Cierra Jackson: Photo by Marco Sanchez

As always it was the patients who surprised us. One, Cierra Danielle Jackson, talked about what it was like to be cured of her sickle cell disease. I think it’s fair to say that most in the audience expected Cierra to talk about her delight at no longer having the crippling and life-threatening condition. And she did. But she also talked about how hard it was adjusting to this new reality.

Cierra said sickle cell disease had been a part of her life for all her life, it shaped her daily life and her relationships with her family and many others. So, to suddenly have that no longer be a part of her caused a kind of identity crisis. Who was she now that she was no longer someone with sickle cell disease?

She talked about how people with most diseases were normal before they got sick, and will be normal after they are cured. But for people with sickle cell, being sick is all they have known. That was their normal. And now they have to adjust to a new normal.

It was a powerful reminder to everyone that in developing new treatments we have to consider the whole person, their psychological and emotional sides as well as the physical.

CIRM’s Dr. Maria Millan (right) at a panel presentation at the Stanford Drug Discovery Symposium. Panel from left to right are: James Doroshow, NCI; Sandy Weill, former CEO Citigroup; Allan Jones, CEO Allen Institute

And so on to the third event we were part of, the Stanford Drug Discovery Symposium. This was a high level, invitation-only scientific meeting that included some heavy hitters – such as Nobel Prize winners Paul Berg and  Randy Schekman, former FDA Commissioner Robert Califf. Over the course of two days they examined the role that philanthropy plays in advancing research, the increasingly important role of immunotherapy in battling diseases like cancer and how tools such as artificial intelligence and big data are shaping the future.

CIRM’s President and CEO, Dr. Maria Millan, was one of those invited to speak and she talked about how California’s investment in stem cell research is delivering Something Better than Hope – which by a happy coincidence is the title of our 2018 Annual Report. She highlighted some of the 51 clinical trials we have funded, and the lives that have been changed and saved by this research.

The presentations at these conferences and workshops are important, but so too are the conversations that happen outside the auditorium, over lunch or at coffee. Many great collaborations have happened when scientists get a chance to share ideas, or when researchers talk to patients about their ideas for a successful clinical trial.

It’s amazing what happens when you bring people together who might otherwise never have met. The ideas they come up with can change the world.

Stanford scientist uses CRISPR-Cas9 and stem cells to develop potential “bubble baby” therapy

Dr. Matthew Porteus, professor of pediatrics at Stanford University.
Photo courtesy of Stanford Medicine.

Our immune system is an important and essential part of everyday life. It is crucial for fighting off colds and, with the help of vaccinations, gives us immunity to potentially lethal diseases. Unfortunately, for some infants, this innate bodily defense mechanism is not present or is severely lacking in function.

This condition is known as severe combined immunodeficiency (SCID), commonly nicknamed “bubble baby” disease because of the sterile plastic bubble these infants used to be placed in to prevent exposure to bacteria, viruses, and fungi that can cause infection. There are several forms of SCID, one of which involves a single genetic mutation on the X chromosome and is known as SCID-X1

Many infants with SCID-X1 develop chronic diarrhea, a fungal infection called thrush, and skin rashes. Additionally, these infants grow slowly in comparison to other children. Without treatment, many infants with SCID-X1 do not live beyond infancy.

SCID-X1 occurs almost predominantly in males since they only carry one X chromosome, with at least 1 in 50,000 baby boys born with this condition. Since females carry two X chromosomes, one inherited from each parent, they are unlikely to inherit two X chromosomes with the mutation present since it would require the father to have SCID-X1.

What if there was a way to address this condition by correcting the single gene mutation? Dr. Matthew Porteus at Stanford University is leading a study that has developed an approach to treat SCID-X1 that utilizes this concept.

By using CRISPR-Cas9 technology, which we have discussed in detail in a previous blog post, it is possible to delete a problematic gene and insert a corrected gene. Dr. Porteus and his team are using CRISPR-Cas9 to edit blood stem cells, which give rise to immune cells, which are the foundation of the body’s defense mechanism. In a study published in Nature, Dr. Porteus and his team have demonstrated proof of concept of this approach in an animal model.

The Stanford team was able to take blood stem cells from six infants with SCID-X1 and corrected them with CRISPR-Cas9. These corrected stem cells were then introduced into mice modeled to have SCID-X1. It was found that these mice were not only able to make immune cells, but many of the edited stem cells maintained their ability to continuously create new blood cells.

In a press release, Dr. Mara Pavel-Dinu, a member of the research team, said:

“To our knowledge, it’s the first time that human SCID-X1 cells edited with CRISPR-Cas9 have been successfully used to make human immune cells in an animal model.”

CIRM has previously awarded Dr. Porteus with a preclinical development award aimed at developing gene correction therapy for blood stem cells for SCID-X1. In addition to this, CIRM has funded two other projects conducted by Dr. Porteus related to CRISPR-Cas9. One of these projects used CRISPR-Cas 9 to develop a treatment for chronic sinusitis due to cystic fibrosis and the second project used the technology to develop an approach for treating sickle cell disease.

CIRM has also funded four clinical trials related to SCID. Two of these trials are related to SCID-X1, one being conducted at St. Jude Children’s Research Hospital and the other at Stanford University. The third trial is related to a different form of SCID known as ADA-SCID and is being conducted at UCLA in partnership with Orchard Therapeutics. Finally, the last of the four trials is related to an additional form of SCID known as ART-SCID and is being conducted at UCSF.

Antibody effective in cure for rare blood disorders

3D illustration of an antibody binding to a designated target.
Illustration created by Audra Geras.

A variety of diseases can be traced to a simple root cause: problems in the bone marrow. The bone marrow contains specialized stem cells known as hematopoietic stem cells (HSCs) that give rise to different types of blood cells. As mentioned in a previous blog about Sickle Cell Disease (SCD), one problem that can occur is the production of “sickle like” red blood cells. In blood cancers like leukemia, there is an uncontrollable production of abnormal white blood cells. Another condition, known as myelodysplastic syndromes (MDS), are a group of cancers in which immature blood cells in the bone marrow do not mature and therefore do not become healthy blood cells.

For diseases that originate in the bone marrow, one treatment involves introducing healthy HSCs from a donor or gene therapy. However, before this type of treatment can take place, all of the problematic HSCs must be eliminated from the patient’s body. This process, known as pre-treatment, involves a combination of chemotherapy and radiation, which can be extremely toxic and life threatening. There are some patients whose condition has progressed to the point where their bodies are not strong enough to withstand pre-treatment. Additionally, there are long-term side effects that chemotherapy and radiation can have on infant children that are discussed in a previous blog about pediatric brain cancer.

Could there be a targeted, non-toxic approach to eliminating unwanted HSCs that can be used in combination with stem cell therapies? Researchers at Stanford say yes and have very promising results to back up their claim.

Dr. Judith Shizuru and her team at Stanford University have developed an antibody that can eliminate problematic blood forming stem cells safely and efficiently. The antibody is able to identify a protein on HSCs and bind to it. Once it is bound, the protein is unable to function, effectively removing the problematic blood forming stem cells.

Dr. Shizuru is the senior author of a study published online on February 11th, 2019 in Blood that was conducted in mice and focused on MDS. The results were very promising, demonstrating that the antibody successfully depleted human MDS cells and aided transplantation of normal human HSCs in the MDS mouse model.

This proof of concept holds promise for MDS as well as other disease conditions. In a public release from Stanford Medicine, Dr. Shizuru is quoted as saying, “A treatment that specifically targets only blood-forming stem cells would allow us to potentially cure people with diseases as varied as sickle cell disease, thalassemia, autoimmune disorders and other blood disorders…We are very hopeful that this body of research is going to have a positive impact on patients by allowing better depletion of diseased cells and engraftment of healthy cells.”

The research mentioned was partially funded by us at CIRM. Additionally, we recently awarded a $3.7 million dollar grant to use the same antibody in a human clinical trial for the so-called “bubble baby disease”, which is also known as severe combined immunodeficiency (SCID). You can read more about that award on a previous blog post linked here.

CIRM Invests in Chemotherapy-Free Approach to Rare But Deadly Childhood Disease

David Vetter, boy diagnosed with SCID

Imagine being told that your seemingly healthy newborn baby has a life-threatening disease. In a moment your whole world is turned upside down. That’s the reality for families with a child diagnosed with severe combined immunodeficiency (SCID). Children with SCID lack a functioning immune system so even a simple cold can prove fatal. Today the governing Board of the California Institute for Regenerative Medicine (CIRM) awarded $3.7 million to develop a new approach that could help these children.

The funding will enable Stanford’s Dr. Judith Shizuru to complete an earlier CIRM-funded Phase 1 clinical trial using a chemotherapy-free transplant procedure for SCID.

Dr. Judy Shizuru: Photo courtesy Stanford University

The goal of the project is to replace SCID patients’ dysfunctional immune cells with healthy ones using a safer form of bone marrow transplant (BMT). Current BMT procedures use toxic chemotherapy to make space in the bone marrow for the healthy transplanted stem cells to take root and multiply. The Stanford team is testing a safe, non-toxic monoclonal antibody that targets and removes the defective blood forming stem cellsin order to promote the engraftment of the transplanted stem cells in the patient. 

The funding is contingent on Dr. Shizuru raising $1.7 million in co-funding by May 1 of this year. 

“This research highlights two of the things CIRM was created to do,” says Maria T. Millan, MD, President & CEO of CIRM. “We fund projects affecting small numbers of patients, something many organizations or companies aren’t willing to do, and we follow those projects from the bench to the bedside, supporting them every step along the way.”

Early testing has shown promise in helping patients and it’s hoped that if this approach is successful in children with SCID it may also open up similar BMT therapies for patients with other auto-immune diseases such as multiple sclerosis, lupus or diabetes.

A new stem cell derived tool for studying brain diseases

Sergiu Pasca’s three-dimensional culture makes it possible to watch how three different brain-cell types – oligodendrocytes (green), neurons (magenta) and astrocytes (blue) – interact in a dish as they do in a developing human  brain.
Courtesy of the Pasca lab

Neurological diseases are among the most daunting diagnoses for a patient to receive, because they impact how the individual interacts with their surroundings. Central to our ability to provide better treatment options for these patients, is scientists’ capability to understand the biological factors that influence disease development and progression. Researchers at the Stanford University School of Medicine have made an important step in providing neuroscientists a better tool to understand the brain.

While animal models are excellent systems to study the intricacies of different diseases, the ability to translate any findings to humans is relatively limited. The next best option is to study human stem cell derived tissues in the laboratory. The problem with the currently available laboratory-derived systems for studying the brain, however, is the limited longevity and diversity of neuronal cell types. Dr. Sergiu Pasca’s team was able to overcome these hurdles, as detailed in their study, published in the journal Nature Neuroscience.

A new approach

Specifically, Dr. Pasca’s group developed a method to differentiate or transform skin derived human induced pluripotent stem cells (iPSCs – which are capable of becoming any cell type) into brain-like structures that mimic how oligodendrocytes mature during brain development. Oligodendrocytes are most well known for their role in myelinating neurons, in effect creating a protective sheath around the cell to protect its ability to communicate with other brain cells. Studying oligodendrocytes in culture systems is challenging because they arise later in brain development, and it is difficult to generate and maintain them with other cell types found in the brain.

These scientists circumvented this problem by using a unique combination of growth factors and nutrients to culture the oligodendrocytes, and found that they behaved very similarly to oligodendrocytes isolated from humans. Most excitingly, they observed that the stem cell-derived oligodendrocytes were able to myelinate other neurons in the culture system. Therefore they were both physically and functionally similar to human oligodendrocytes.

Importantly, the scientists were also able to generate astrocytes alongside the oligodendrocytes. Astrocytes perform many important functions such as providing essential nutrients and directing the electrical signals that help cells in the brain communicate with each other. In a press release, Dr. Pasca explains the importance of generating multiple cell types in this in vitro system:

“We now have multiple cell types interacting in one single culture. This permits us to look close-up at how the main cellular players in the human brain are talking to each other.”

This in vitro or laboratory-developed system has the potential to help scientists better understand oligodendrocytes in the context of diseases such as multiple sclerosis and cerebral palsy, both of which stem from improper myelination of brain nerve cells.

This work was partially supported by a CIRM grant.

Rare Disease Gets Big Boost from California’s Stem Cell Agency

UC Irvine’s Dr. Leslie Thompson and patient advocate Frances Saldana after the CIRM Board vote to approve funding for Huntington’s disease

If you were looking for a poster child for an unmet medical need Huntington’s disease (HD) would be high on the list. It’s a devastating disease that attacks the brain, steadily destroying the ability to control body movement and speech. It impairs thinking and often leads to dementia. It’s always fatal and there are no treatments that can stop or reverse the course of the disease. Today the Board of the California Institute for Regenerative Medicine (CIRM) voted to support a project that shows promise in changing that.

The Board voted to approve $6 million to enable Dr. Leslie Thompson and her team at the University of California, Irvine to do the late stage testing needed to apply to the US Food and Drug Administration for permission to start a clinical trial in people. The therapy involves transplanting stem cells that have been turned into neural stem cells which secrete a molecule called brain-derived neurotrophic factor (BDNF), which has been shown to promote the growth and improve the function of brain cells. The goal is to slow down the progression of this debilitating disease.

“Huntington’s disease affects around 30,000 people in the US and children born to parents with HD have a 50/50 chance of getting the disease themselves,” says Dr. Maria T. Millan, the President and CEO of CIRM. “We have supported Dr. Thompson’s work for a number of years, reflecting our commitment to helping the best science advance, and are hopeful today’s vote will take it a crucial step closer to a clinical trial.”

Another project supported by CIRM at an earlier stage of research was also given funding for a clinical trial.

The Board approved almost $12 million to support a clinical trial to help people undergoing a kidney transplant. Right now, there are around 100,000 people in the US waiting to get a kidney transplant. Even those fortunate enough to get one face a lifetime on immunosuppressive drugs to stop the body rejecting the new organ, drugs that increase the risk for infection, heart disease and diabetes.  

Dr. Everett Meyer, and his team at Stanford University, will use a combination of healthy donor stem cells and the patient’s own regulatory T cells (Tregs), to train the patient’s immune system to accept the transplanted kidney and eliminate the need for immunosuppressive drugs.

The initial group targeted in this clinical trial are people with what are called HLA-mismatched kidneys. This is where the donor and recipient do not share the same human leukocyte antigens (HLAs), proteins located on the surface of immune cells and other cells in the body. Around 50 percent of patients with HLA-mismatched transplants experience rejection of the organ.

In his application Dr. Meyer said they have a simple goal: “The goal is “one kidney for life” off drugs with safety for all patients. The overall health status of patients off immunosuppressive drugs will improve due to reduction in side effects associated with these drugs, and due to reduced graft loss afforded by tolerance induction that will prevent chronic rejection.”

Early CIRM support helps stem cell pioneer develop promising new therapy for cancer

Irv Weissman

Irv Weissman, Ph.D., Photo: courtesy Stanford University

When you get praise from someone who has been elected to the National Academy of Sciences and has been named California Scientist of the Year you know you must be doing something right.

That’s how we felt the other day when Irv Weissman, Director of the Stanford Institute of Stem Cell Biology and Regenerative Medicine, issued a statement about how important the support of CIRM was in advancing his research.

The context was the recent initial public offering (IPO) of Forty Seven Inc.. a company co-founded by Dr. Weissman. That IPO followed news that two Phase 2 clinical trials being run by Forty Seven Inc. were demonstrating promising results against hard-to-treat cancers.

Dr. Weissman says the therapies used a combination of two monoclonal antibodies, 5F9 from Forty Seven Inc. and Rituximab (an already FDA-approved treatment for cancer and rheumatoid arthritis) which:

“Led to about a 50% overall remission rate when used on patients who had relapsed, multi-site disease refractory to rituximab-plus-chemotherapy. Most of those patients have shown a complete remission, although it’s too early to tell if this is complete for life.”

5F9 attacks a molecule called CD47 that appears on the surface of cancer cells. Dr. Weissman calls CD47 a “don’t eat me signal” that protects the cancer against the body’s own immune system. By blocking the action of CD47, 5F9 strips away that “don’t eat me signal” leaving the cancer vulnerable to the patient’s immune system. We have blogged about this work here and here.

The news from these trials is encouraging. But what was gratifying about Dr. Weissman’s statement is his generosity in sharing credit for the work with CIRM.

Here is what he wrote:

“What is unusual about Forty Seven is that not only the discovery, but its entire preclinical development and testing of toxicity, etc. as well as filing two Investigational New Drug [IND] applications to the Food and Drug Administration (FDA) in the US and to the MHRA in the UK, as well as much of the Phase 1 trials were carried out by a Stanford team led by two of the discoverers, Ravi Majeti and Irving Weissman at Stanford, and not at a company.

The major support came from the California Institute of Regenerative Medicine [CIRM], funded by Proposition 71, as well as the Ludwig Cancer Research Foundation at the Ludwig Center for Cancer Stem Cell Research at Stanford. CIRM will share in downstream royalties coming to Stanford as part of the agreement for funding this development.

This part of the state initiative, Proposition 71, is highly innovative and allows the discoverers of a field to guide its early phases rather than licensing it to a biotech or a pharmaceutical company before the value and safety of the discovery are sufficiently mature to be known. Most therapies at early-stage biotechs are lost in what is called the ‘valley of death’, wherein funding is very difficult to raise; many times the failure can be attributed to losing the expertise of the discoverers of the field.”

Dr. Weissman also had praise for CIRM’s funding model which requires companies that produce successful, profitable therapies – thanks to CIRM support – to return a portion of those profits to California. Most other funding agencies don’t have those requirements.

“US federal funds, from agencies such as the National Institutes of Health (NIH) similarly support discovery but cannot fund more than a few projects to, and through, early phase clinical trials. And, under the Bayh-Dole Act, the universities keep all of the equity and royalties derived from licensing discoveries. In that model no money flows back to the agency (or the public), and nearly a decade of level or less than level funding (at the national level) has severely reduced academic research. So this experiment of funding (the NIH or the CIRM model) is now entering into the phase that the public will find out which model is best for bringing new discoveries and new companies to the US and its research and clinical trials community.”

We have been funding Dr. Weissman’s work since 2006. In fact, he was one of the first recipients of CIRM funding.  It’s starting to look like a very good investment indeed.

 

Can stem cells help people recovering from a stroke? You asked, and the experts answered

FacebookLive_AskExperts_Stroke_IMG_1656

We recently held our first ever Facebook Live event. It was focused on the use of stem cells and recovery from a stroke and featured three great guests: Dr. Gary Steinberg, chief of Neurosurgery at Stanford, Sonia Coontz, a patient of Dr. Steinberg’s, and CIRM’s own Science Officer Dr. Lila Collins.

We had an amazing response from people during the event and in the days since then with some 6,750 people watching the video and almost 1,000 people reacting by posting a comment or sharing it with friends. It was one of the most successful things we have ever done on Facebook so it’s not surprising that we plan on doing many more Facebook Live ‘Ask the Expert’ events in the future. We will post more details of that as we finalize them.

We tried to cover as many topics as possible during the hour but there were simply too many questions for us to get to all of them. So here is a recap of the key issues we covered, and a few we didn’t have a chance to answer.

Let’s start with Dr. Steinberg’s explanation of the research that led to his current clinical trial:

Dr. Steinberg: “I got interested in this about 18 years ago when I took human cells and transplanted them into rodent models of stroke. What we found was that when we transplanted those cells into the stroke region, the core of the stroke, they didn’t survive very well but when we moved them a few millimeters away from the stroke they not only survived but they migrated to the stroke.

The reason they migrate is that the stem cells have receptors on them that interact with chemicals given off by the stroke environment and that’s why they migrate to the stroke site. And when they get to the site they can turn into different kinds of cells. Very importantly we found these mice and rats that had behavioral problems – walking, moving – as a result of the stroke, we found we could improve their neurological outcomes with the stem cells.

With the help of CIRM, which has been very generous, we were fortunate enough to receive about $24 million in funding over the last 8 years, from 2010, to move this therapy into the clinic to understand the basic mechanisms of the recovery and to start clinical trials

One of the surprising things was that our initial notion was that the cells we transplanted into the brains would initially turn into the cells in the brain affected by the stroke and reconstitute those circuits. We were shocked to find that that was not what was happening, that only a few of the transplanted cells turned into neurons. The way they were recovering function was by secreting very powerful growth factors and molecules and proteins that enhanced native recovery or the ability of the normal brain to recover itself. Some of these processes included outgrowth of neurons, new connections, new synapses, not from the stem cells but from the native cells already in the brain.

This is not cell replacement but enhancing native recovery and, in a simple sense, what the cells are doing, we believe, is to change the adult brain, which has a hard time recovering from a stroke, into an infant brain and infants recover very well after a stroke.”

All this work was focused on ischemic strokes, where a blockage cuts off blood flow to the brain. But people like Cheryl Ward wanted to know: “Will this work for hemorrhagic stroke?” That’s where a blood vessel in the brain leaks or ruptures.

Dr. Steinberg: “I suspect we will be generalizing this therapy into hemorrhagic patients very, very soon and there’s no reason why it shouldn’t work there. The reason we didn’t start there is that 85% of strokes are ischemic and only 15% are hemorrhagic so it’s a smaller population but a very, very important population because when patients have a hemorrhage from a stroke they are often more seriously disabled than from ischemic.”

Dr. Lila Collins: “I would like to highlight one trial for hemorrhagic stroke with the Mayo Clinic and that’s using mesenchymal stem cells (normally found in bone marrow or blood). It’s an early stage, Phase 1 safety study in patients with recent cerebral hemorrhage.  They are looking at improvements in neurological function and patients have to be treated within 72 hours after the stroke.”

Dr. Steinberg explained that because it’s more difficult to enroll patients within 72 hours of a stroke that we may end up offering a combination of therapies spread out over months or even years.

Dr. Steinberg: “It may be that and we may figure this out in the next 5 to 10 years, that you might want to treat patients acutely (right away) with an intravenous therapy in the first 72 hours and then you might want to come in again sub-acutely within a few months, injecting the cells into the brain near the stroke, and then maybe come in chronically a few years later if there are still problems and place the cells directly in the brain. So, lots of ways to think about how to use this in the future.”

James Russell suffered a stroke in 2014 and wrote:

“My left side was affected. My vision was also impacted. Are any stroke patients being given stem cells seeing possible improvement in visual neglect?”

Dr. Steinberg: “We don’t know the answer to that yet, it’s quite possible. It’s true these vision circuits are not dead and could be resurrected. We have not targeted visual pathways in our work, we have targeted motor functions, but I would also be optimistic that we could target patients who have vision problems from stroke. It’s a very important area.

A number of people wondered if stem cells can help people recovering from a stroke can they also help people with other neurological conditions.

Hanifa Gaphoor asked “What about Parkinson’s disease?” and Ginnievive Patch wondered “Do you feel hopeful for neurological illnesses like Huntington’s disease and ALS? Dr. Steinberg was cautiously optimistic.

Dr. Steinberg: “We’ve extended this kind of treatment not just for ischemic stroke but into traumatic brain injury (TBI) and we just completed a trial for patients with chronic TBI or who have suffered a trauma to the brain. Many other indications may be possible. In fact, now that we know these circuits are not dead or irreversibly injured, we believe we could even extend this to neurodegenerative diseases like ALS, Parkinson’s, maybe even to Alzheimer’s disease in the future. So, lots of hope but we don’t want to oversell this, and we want to make sure this is done in a rigorous fashion.”

Several people had questions about using their own adipose, or fat stem cells, in therapies being offered at clinics around the US and in other countries. Cheri Hicks asked: “I’m curious if adipose stem cell being used at clinics at various places is helpful or beneficial?”

Dr. Steinberg: “I get emails or calls from patients every week saying should I go to Russia, India or Mexico and get stem cell transplants which are done not as part of a rigorous trial and I discourage patients from getting stem cells that are not being given in a controlled fashion. For one thing, patients have been getting hurt by these treatments in these clinics; they have developed tumors and infections and other problems. In many cases we don’t even know what the cells are, there’s not published information and the patients pay cash for this, of course.”

At CIRM we also worry about people going to clinics, in the US and in other countries, where they are getting therapies that have not been approved by the US Food and Drug Administration (FDA) or other appropriate regulatory bodies. That’s why we have created this page on our website to help people who want a stem cell therapy but don’t know what to look for in a clinical trial or what questions to ask to make sure it’s a legitimate trial, one that’s been given the go-ahead by the FDA.

Bret Ryan asked: “What becomes of the implanted cells?”

Dr. Steinberg: We found after transplanting the cells, one week after the transplant, we see a new abnormality in the premotor cortex, the area of the brain that controls motor function. We saw a new abnormality there or a new signal that disappears after a month and never comes back. But the size of that temporary abnormality after one week correlates very closely with the degree of recovery after six months, one year and two years.

One of the interesting things is that it doesn’t seem to be necessary for the cells to survive long term to have beneficial effects. The cells we used in the SanBio trial don’t survive more than a month and yet they seem to aid recovery function in our pilot studies which is sustained for years.”

And of course, many people, such as Karen Smart, wanted to know how they could get the therapy. Right now, the clinical trial is fully enrolled but Stanford is putting together a waiting list for future trials. If you are interested and would like more information, please email: stemcellstudy@stanford.edu.

Sonia Coontz, the patient who was also a key part of the Facebook Live event, has an amazing story to tell. She was left devastated, physically and emotionally, after having a stroke. But then she heard about Dr. Steinberg’s clinical trial and it changed her life. Here’s her story.

We were thrilled to receive all of your comments and questions during our first Facebook Live event. It’s this kind of dialogue between scientists, patients and the public that will be critical for the continued support of our mission to accelerate stem cell treatments to patients with unmet medical needs.

Due to the response, we plan to regularly schedule these “Ask the Expert” events. What disease area would you like us to focus on next time? Leave us a comment or email info@cirm.ca.gov

 

Can stem cells help people recover from a stroke? Join us for a Facebook Live event this Thursday, May 31 for the answers

AskExpertsMAY2018[1]

Stroke is one of the leading causes of death in the US and the leading cause of serious, long-term disability. But could stem cell therapies change that and help people who’ve had a brain attack?  Could stem cells help repair the damage caused by a stroke and restore a person’s ability to speak normally, to be able to walk without a limp or regain strength in their hands and arms?

To find out the answers to these and other questions joins us for “Ask the Expert”, a special Facebook Live event this Thursday, May 31, from noon till 1pm PDT

 The event will feature Dr. Gary Steinberg, the Chair of Neurosurgery at Stanford University. Dr. Steinberg is currently running a CIRM-funded clinical trial targeting stroke.

We will also be joined by CIRM Senior Science Officer Lila Collins, PhD who can talk about the broad range of other projects using stem cells to help people recover from a stroke.

We are also delighted to welcome Sonia Coontz, who suffered a devastating stroke several years ago and made a remarkable recovery after getting a stem cell therapy.

To join us for the event, all you have to do is go to our Facebook page on Thursday at noon (PDT) and you should see a video playing, which you can watch on mobile or desktop. Click the video to enter viewing mode.

Also, make sure to “like” our page before the event to receive a notification that we’ve gone live.

And we want to hear from you, so you will be able to post questions for the experts to answer or, you can email them directly to us at info@cirm.ca.gov

We look forward to seeing you there.