The use of antiretroviral drugs has turned HIV/AIDS from a fatal disease to one that can, in many cases in the US, be controlled. But these drugs are not a cure. That’s why the governing Board of the California Institute for Regenerative Medicine (CIRM) voted to approve investing $6.85 million in a therapy that aims to cure the disease.
This is the 82nd clinical trial funded by CIRM.
There are approximately 38 million people worldwide living with HIV/AIDS. And each year there are an estimated 1.5 million new cases. The vast majority of those living with HIV do not have access to the life-saving antiretroviral medications that can keep the virus under control. People who do have access to the medications face long-term complications from them including heart disease, bone, liver and kidney problems, and changes in metabolism.
The antiretroviral medications are effective at reducing the viral load in people with HIV, but they don’t eliminate it. That’s because the virus that causes AIDS can integrate its DNA into long-living cells in the body and remain dormant. When people stop taking their medications the virus is able to rekindle and spread throughout the body.
Dr. William Kennedy and the team at Excision Bio Therapeutics have developed a therapeutic candidate called EBT-101. This is the first clinical study using the CRISPR-based platform for genome editing and excision of the latent form of HIV-1, the most common form of the virus that causes AIDS in the US and Europe. The goal is to eliminate or sufficiently reduce the hidden reservoirs of virus in the body to the point where the individual is effectively cured.
“To date only a handful of people have been cured of HIV/AIDS, so this proposal of using gene editing to eliminate the virus could be transformative,” says Dr. Maria Millan, President and CEO of CIRM. “In California alone there are almost 140,000 people living with HIV. HIV infection continues to disproportionately impact marginalized populations, many of whom are unable to access the medications that keep the virus under control. A functional cure for HIV would have an enormous impact on these communities, and others around the world.”
In a news release announcing they had dosed the first patient, Daniel Dornbusch, CEO of Excision, called it a landmark moment. “It is the first time a CRISPR-based therapy targeting an infectious disease has been administered to a patient and is expected to enable the first ever clinical assessment of a multiplexed, in vivo gene editing approach. We were able to reach this watershed moment thanks to years of innovative work by leading scientists and physicians, to whom we are immensely grateful. With this achievement, Excision has taken a major step forward in developing a one-time treatment that could transform the HIV pandemic by freeing affected people from life-long disease management and the stigma of disease.”
The Excision Bio Therapeutics team also scored high on their plan for Diversity, Equity and Inclusion. Reviewers praised them for adding on a partnering organization to provide commitments to serve underserved populations, and to engaging a community advisory board to help guide their patient recruitment.
For children born with severe combined immunodeficiency (SCID) life can be very challenging. SCID means they have no functioning immune system, so even a simple infection can prove life threatening. Left untreated, children with SCID often die in the first few years of life.
There are stem cell/gene therapies funded by the California Institute for Regenerative Medicine (CIRM), such as ones at UCLA and UCSF/St. Judes, but an alternative method of treating, and even curing the condition, is a bone marrow or hematopoietic stem cell transplant (HCT). This replaces the child’s blood supply with one that is free of the SCID mutation, which helps restore their immune system.
However, current HCT methods involve the use of chemotherapy or radiation to destroy the patient’s own unhealthy blood stem cells and make room for the new, healthy ones. This approach is toxic and complex and can only be performed by specialized teams in major medical centers, making access particularly difficult for poor and underserved communities.
To change that, Dr. Judy Shizuru at Stanford University, with CIRM funding, developed an antibody that can direct the patient’s own immune cells to kill diseased blood stem cells, creating the room needed to transplant new, healthy cells. The goal was to make stem cell transplants safer and more effective for the treatment of many life-threatening blood disorders.
That approach, JSP191, is now being championed by Jasper Therapeutics and they just got some very good news from the Food and Drug Administration (FDA). The FDA has granted JSP191 Fast Track Designation, which can speed up the review of therapies designed to treat serious conditions and fill unmet medical needs.
In a news release, Ronald Martell, President and CEO of Jasper Therapeutics, said this is good news for the company and patients: “This new Fast Track designation recognizes the potential role of JSP191 in improving clinical outcomes for these patients and will allow us to more closely work with the FDA in the upcoming months to determine a path toward a Biologics License Application (BLA) submission.”
Getting a BLA means Jasper will be able to market the antibody in the US and make it available to all those who need it.
This is the third boost from the FDA for Jasper. Previously the agency granted JSP191 both Orphan and Rare Pediatric Disease designations. Orphan drug designation qualifies sponsors for incentives such as tax credits for clinical trials. Rare Pediatric Disease designation means that if the FDA does eventually approve JSP191, then Jasper can apply to receive a priority review of an application to use the product for a different disease, such as someone who is getting a bone marrow transplant for sickle cell disease or severe auto immune diseases.
For more than a decade, the California Institute for Regenerative Medicine (CIRM) has funded educational and research training programs to give students the opportunity to explore regenerative medicine and stem cell science right here in California.
This summer, the CIRM team was thrilled to meet the bright scientists taking part in this year’s Bridges to Stem Cell Research Program, which culminated at the 2022 Bridges Trainee Meeting in sunny San Diego.
Started in 2009, the Bridges program provides paid stem cell research internships to students at universities and colleges that don’t have major stem cell research programs. Each Bridges internship includes thorough hands-on training and education in regenerative medicine and stem cell research, and direct patient engagement and outreach activities that engage California’s diverse communities.
To date, there are 1,663 Bridges alumni, and another 109 Bridges trainees are completing their internships in 2022.
In addition to networking with other scientists across the state, the annual Bridges Trainee Meeting provides students the opportunity to share their research in poster presentations and to learn about careers in the regenerative medicine field. This year, students also attended talks about cutting edge science research, anti-racism in STEM, science communication through social media, and patient advocacy.
“As the field advances, we must also meet the demand for promising young scientists,” says Maria T. Millan, M.D., President and CEO of CIRM (pictured below). “The CIRM Bridges programs across the state of California will provide students with the tools and resources to begin their careers in regenerative medicine.”
There are currently 15 active Bridges programs throughout California, each with its own eligibility criteria and application process. If you are interested in applying, please visit this web page for more details about each program. If you have questions about the Bridges program, please email the CIRM Bridges director, Dr. Kelly Shepard at email@example.com.
Finally, a sincere thank you goes to the Bridges Program from California State University, San Marcos for hosting this year’s CIRM Bridges Trainee Meeting!
Check out some of the photos from this year’s conference below.
Almost every day, we hear new reports from the thousands of regenerative medicine clinical trials globally sponsored by hundreds of companies and academic researchers. The California Institute for Regenerative Medicine (CIRM) is a leader in this space supporting some of the most advanced cell and gene therapy clinic trials for a variety of unmet medical needs. With all this current activity, it’s easy to forget that there were only a handful of clinical trials going on just seven years ago.
A New System for Delivering Treatments
In 2015, CIRM’s leadership recognized that we were on the cusp of introducing an array of new regenerative medicine clinical trials. However, there was one big concern—the existing clinical delivery systems had limited experience and capacity for managing these new and comparatively complex clinical trials. Cell and gene therapy regenerative medicine treatments require new systems for manufacturing, processing, and delivering treatments to patients.
In anticipation of the need for clinical bandwidth to support clinical trials, CIRM funded a network of California medical centers to develop teams dedicated to supporting regenerative medicine clinical trials. This network was called the Alpha Clinics Network.
Since 2015, the Alpha Clinics Network has grown to include six academic medical centers in California. The Network has treated over a thousand patients in more than 100 clinical trials. CIRM frequently encounters companies and academic researchers that are specifically interested in bringing their research to California to be performed in the Alpha Clinics Network. These research sponsors cite expertise in manufacturing, process, delivery and regulatory compliance as the Networks value proposition. One sponsor summed it up by indicating there are “fewer protocol deviations (errors)” in the Alpha Clinics.
Expanding the Alpha Clinics Network
As we enter 2022 with CIRM’s new five year strategic plan, a major aim is to create a broad network of medical centers capable of supporting diverse patient participation in clinical trials.
As a first step in this effort, CIRM recently announced $80 million in funding to expand the Alpha Clinics Network. This funding is intended to expand both the scale and scope of the Network. This funding will allow the scale to grow from six medical center to up to ten. Scale is important because as the number of clinical trials grow, there needs to be increased coordination and sharing of the workload. Alpha Clinic sites already collaborate to conduct individual clinical trials, and an expanded network will enable a greater number of trials to occur simultaneously.
In addition, the Expansion Awards will enable the Network to expand the scope of its activities to address current needs of the field. These needs include new research platforms for conducting clinical trials. For example, sites are looking at integrating new types of genomic (DNA sequencing) tools to support improved diagnosis and treatment of patients.
Also, CIRM is committed to funding research to treat neurological diseases. We anticipate network sites will develop advanced systems for delivering treatments to patients and evaluating the effectiveness of these treatments. In addition, sites will be developing training programs to address the growing workforce needs of the field of regenerative medicine.
In 2015, CIRM invested in the Alpha Clinics Network which positioned California as a leader in supporting regenerative medicine clinical trials. In 2022, we will be expanding the Network with the aim of delivering transformative treatments to a diverse California and the world. The Network will fulfill this aim by expanding its reach in the state, developing advanced research planforms and technologies, and by training the next generations of researchers with the skills to deliver patient treatments.
Watch a recording of our recent Alpha Clinics concept plan webinar:
This year was a momentous one for the California Institute for Regenerative Medicine (CIRM). We celebrated the passage of Proposition 14, and as a result, introduced our new strategic plan and added a group of talented individuals to our team.
We shared our most exciting updates and newsworthy stories—topics ranging from stem cell research to diversity in science—right here on The Stem Cellar. Nearly 100,000 readers followed along throughout the year!
In case you missed them, here’s a recap of our most popular blogs of 2021. We look forward to covering even more topics in 2022 and send a sincere thank you to our wonderful Stem Cellar readers for tuning in!
- Type 1 Diabetes Therapy Gets Go-Ahead for Clinical Trial
This past year, ViaCyte and CRISPR Therapeutics put their heads together to develop a novel treatment for type 1 diabetes (T1D). The result was an implantable device containing embryonic stem cells that develop into pancreatic progenitor cells, which are precursors to the islet cells destroyed by T1D. The hope is that when this device is transplanted under a patient’s skin, the progenitor cells will develop into mature insulin-secreting cells that can properly regulate the glucose levels in a patient’s blood.
- CIRM Builds Out World Class Team With 5 New hires
After the Passage of Proposition 14 in 2020, CIRM set ambitious goals as part of our new strategic plan. To help meet these goals and new responsibilities, we added a new group of talented individuals with backgrounds in legal, finance, human resources, project management, and more. The CIRM team will continue to grow in 2022, as we add more team members who will work to fulfil our mission of accelerating world class science to deliver transformative regenerative medicine treatments in an equitable manner to a diverse California and world.
- Meet Xenobots 2.0 – the Next Generation of Living Robots
In 2020, we wrote about how researchers at the University of Vermont and Tufts University were able to create what they call xenobots – the world’s first living, self-healing robots created from frog stem cells. Fast forward to 2021: the same team created an upgraded version of these robots that they have dubbed Xenobots 2.0. These upgraded robots can self-assemble a body from single cells, do not require muscle cells to move, and demonstrate the capability to record memory. Interesting stuff!
- CIRM Board Approves New Clinical Trial for ALS
In June, CIRM’s governing Board awarded $11.99 million to Cedars-Sinai to fund a clinical trial for amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease. Clive Svendsen, Ph.D. and his team will be conducting a trial that uses a combined cell and gene therapy approach as a treatment for ALS. The trial builds upon CIRM’s first ALS trial, also conducted by Cedars-Sinai and Svendsen.
- COVID is a Real Pain in the Ear
Viral infections are a known cause of hearing loss and other kinds of infection. That’s why before the pandemic started, Dr. Konstantina Stantovic at Massachusetts Eye and Ear and Dr. Lee Gherke at MIT had been studying how and why things like measles, mumps and hepatitis affected people’s hearing. After COVID hit, they heard reports of patients experiencing sudden hearing loss and other problems, so they decided to take a closer look.
And there you have it: The Stem Cellar’s top blog posts of 2021! If you’re looking for more ways to get the latest updates from The Stem Cellar and CIRM, follow us on social media on Facebook, Twitter, LinkedIn, and Instagram.
2020 was, by any standards, a pretty wacky year. Pandemic. Political convulsions. And a huge amount of uncertainty as to the funding of life-saving therapies at CIRM. Happily those all turned out OK. We got vaccines to take care of COVID. The election was won fair and square (seriously). And Proposition 14 was approved by the voters of California, re-funding your favorite state Stem Cell Agency.
But for a while, quite a while, there was uncertainty surrounding our future. For a start, once the pandemic lockdown kicked in it was impossible for people to go out and collect the signatures needed to place Proposition 14 on the November ballot. So the organizers of the campaign reached out online, using petitions that people could print out and sign and mail in.
It worked. But even after getting all the signatures needed they faced problems such as how do you campaign to get something passed, when the normal channels are not available. The answer is you get very creative very quickly.
Bob Klein, the driving force behind both Proposition 71 (the 2004 ballot initiative that created CIRM) and Proposition 14, says it was challenging:
“It was a real adventure. It’s always hard, you have a complicated message about stem cells and genetics and therapy and it’s always a challenge to get a million signatures for a ballot initiative but in the middle of a pandemic where we had to shut down the signature gathering at grocery stores and street corners, where we had to go to petitions that had to be sent to voters and get them to fill them out properly and send them back. And of course the state went into an economic recoil because of the pandemic and people were worried about the money.”
Challenging absolutely, but ultimately successful. On November 13, ten days after the election, Prop 14 was declared the winner.
As our President and CEO, Dr. Maria Millan says, we went from an agency getting ready to close its doors to one ramping up for a whole new adventure.
“We faced many challenges in 2020. CIRM’s continued existence was hinging on the passage of a new bond initiative and we began the year uncertain if it would even make it on the ballot. We had a plan in place to wind down and close operations should additional funding not materialize. During the unrest and challenges brought by 2020, and functioning in a virtual format, we retained our core group of talented individuals who were able to mobilize our emergency covid research funding round, continue to advance our important research programs and clinical trials and initiate the process of strategic planning in the event that CIRM was reauthorized through a new bond initiative. Fortunately, we planned for success and Proposition 14 passed against all odds!”
“When California said “Yes,” the CIRM team was positioned to launch the next Era of CIRM! We have recruited top talent to grow the team and have developed a new strategic plan and evolved our mission: Accelerating world-class science to deliver transformative regenerative medicine treatments to a diverse California and worldwide in an equitable manner.”
And since that close call we have been very busy. In the last year we have hired 16 new employees, everyone from a new General Counsel to the Director of Finance, and more are on the way as we ramp up our ability to turn our new vision into a reality.
We have also been working hard to ensure we could continue to fund groundbreaking research from the early-stage Discovery work, to testing therapies in patients in clinical trials. Altogether our Board has approved almost $250 million in 56 new awards since December 2020. That includes:
Clinical – $84M (9 awards)
Translational – $15M (3 awards)
Discovery – $13M (11 awards)
Education – $138M (33 awards)
We have also enrolled more than 360 new patients in clinical trials that we fund or that are being carried out in the CIRM Alpha Stem Cell Clinic network.
This is a good start, but we know we have a lot more work to do in the coming years.
The last year has flown by and brought more than its fair share of challenges. But the CIRM team has shown that it can rise to those, in person and remotely, and meet them head on. We are already looking forward to 2022. We’ve got a lot of work to do.
There are many unknown elements for what triggers the cells in an embryo to start dividing and multiplying and becoming every single cell in the body. Now researchers at the Gladstone Institutes in San Francisco have uncovered one of those elements, how embryos determine which cells become the head and which the tail.
In this CIRM-funded study the Gladstone team, led by Dr. Todd McDevitt, discovered almost by chance how the cells align in a heads-to-tail arrangement.
They had created an organoid made from brain cells when they noticed that some of the cells were beginning to gather in an elongated fashion, in the same way that spinal cords do in a developing fetus.
In a news article, Nick Elder, a graduate student at Gladstone and the co-author of the study, published in the journal Development, says this was not what they had anticipated would happen: “Organoids don’t typically have head-tail directionality, and we didn’t originally set out to create an elongating organoid, so the fact that we saw this at all was very surprising.”
Further study enabled the team to identify which molecules were involved in signaling specific genes to switch on and off. These were similar to the process previously identified in developing mouse embryos.
“This is such a critical point in the early development of any organism, so having a new model to observe it and study it in the lab is very exciting,” says McDevitt.
This is not just of academic interest either, it could have real world implications in helping understand what causes miscarriages or birth defects.
“We can use this organoid to get at unresolved human developmental questions in a way that doesn’t involve human embryos,” says Dr. Ashley Libby, another member of the team. “For instance, you could add chemicals or toxins that a pregnant woman might be exposed to, and see how they affect the development of the spinal cord.”
A search on Google using the term “stem cell blogs” quickly produces a host of sites offering treatments for everything from ankle, hip and knee problems, to Parkinson’s disease and asthma. Amazingly the therapies for those very different conditions all use the same kind of cells produced in the same way. It’s like magic. Sadly, it’s magic that is less hocus pocus and more bogus bogus.
The good news is there are blogs out there (besides us, of course) that do offer good, accurate, reliable information about stem cells. The people behind them are not in this to make a quick buck selling snake oil. They are in this to educate, inform, engage and enlighten people about what stem cells can, and cannot do.
So, here’s some of our favorites.
This blog has just undergone a face lift and is now as colorful and easy to read as it is informative. It bills itself as the longest running stem cell blog around. It’s run by UC Davis stem cell biologist Dr. Paul Knoepfler – full disclosure, we have funded some of Paul’s work – and it’s a constant source of amazement to me how Paul manages to run a busy research lab and post regular updates on his blog.
The power of The Niche is that it’s easy for non-science folk – like me – to read and understand without having to do a deep dive into Google search or Wikipedia. It’s well written, informative and often very witty. If you are looking for a good website to check whether some news about stem cells is real or suspect, this is a great place to start.
This site is run by another old friend of CIRM’s, Don Reed. Don has written extensively about stem cell research in general, and CIRM in particular. His motivation to do this work is clear. Don says he’s not a doctor or scientist, he’s something much simpler:
“No. I am just a father fighting for his paralyzed son, and the only way to fix him is to advance cures for everyone. Also, my mother died of breast cancer, my sister from leukemia, and I myself am a prostate cancer survivor. So, I have some very personal reasons to support the California Institute for Regenerative Medicine and to want state funding for stem cell and other regenerative medicine research to continue in California!”
The power of Don’s writing is that he always tells human stories, real tales about real people. He makes everything he does accessible, memorable and often very funny. If I’m looking for ways to explain something complex and translate it into everyday English, I’ll often look at Don’s work, he knows how to talk to people about the science without having their eyes cloud over.
This is published by the International Society for Stem Cell Research (ISSCR), the leading professional organization for stem cell scientists. You might expect a blog from such a science-focused organization to be heavy going for the ordinary person, but you’d be wrong.
A Closer Look at Stem Cells is specifically designed for people who want to learn more about stem cells but don’t have the time to get a PhD. They have sections explaining what stem cells are, what they can and can’t do, even a glossary explaining different terms used in the field (I used to think the Islets of Langerhans were small islands off the coast of Germany till I went to this site).
One of the best, and most important, parts of the site is the section on clinical trials, helping people understand what’s involved in these trials and the kinds of things you need to consider before signing up for one.
Of course, the US doesn’t have a monopoly on stem cell research and that’s reflected in the next two choices. One is the Signals Blog from our friends to the north in Canada. This is an easy-to-read site that describes itself as the “Insiders perspective on the world of stem cells and regenerative medicine.” The ‘Categories ‘dropdown menu allows you to choose what you want to read, and it gives you lots of options from the latest news to a special section for patients, even a section on ethical and legal issues.
As you may have guessed from the title this is by our chums across the pond in Europe. They lay out their mission on page one saying they want to help people make sense of stem cells:
“As a network of scientists and academics, we provide independent, expert-reviewed information and road-tested educational resources on stem cells and their impact on society. We also work with people affected by conditions, educators, regulators, media, healthcare professionals and policymakers to foster engagement and develop material that meets their needs.”
True to their word they have great information on the latest research, broken down by different types of disease, different types of stem cell etc. And like CIRM they also have some great educational resources for teachers to use in the classroom.
On March 19th we held a special Facebook Live “Ask the Stem Cell Team About Autism” event. We were fortunate enough to have two great experts – Dr. Alysson Muotri from UC San Diego, and CIRM’s own Dr. Kelly Shepard. As always there is a lot of ground to cover in under one hour and there are inevitably questions we didn’t get a chance to respond to. So, Dr. Shepard has kindly agreed to provide answers to all the key questions we got on the day.
If you didn’t get a chance to see the event you can watch the video here. And feel free to share the link, and this blog, with anyone you think might be interested in the material.
Can umbilical cord blood stem cells help reduce some of the symptoms?
This question was addressed by Dr. Muotri in the live presentation. To recap, a couple of clinical studies have been reported from scientists at Duke University and Sutter Health, but the results are not universally viewed as conclusive. The Duke study, which focused on very young children, reported some improvements in behavior for some of the children after treatment, but it is important to note that this trial had no placebo control, so it is not clear that those patients would not have improved on their own. The Duke team has moved forward with larger trial and placebo control.
Does it have to be the child’s own cord blood or could donated blood work too?
In theory, a donated cord product could be used for similar purposes as a child’s own cord, but there is a caveat- the donated cord tissues must have some level of immune matching with the host in order to not be rejected or lead to other complications, which under certain circumstances, could be serious.
Some clinics claim that the use of fetal stem cells can help stimulate improved blood and oxygen flow to the brain. Could that help children with autism?
Fetal stem cells have been tested in FDA approved/sanctioned clinical trials for certain brain conditions such as stroke and Parkinson Disease, where there is clearer understanding of how and which parts of the brains are affected, which nerve cells have been lost or damaged, and where there is a compelling biological rationale for how certain properties the transplanted cells, such as their anti-inflammatory properties, could provide benefit.
In his presentation, Dr. Muotri noted that neurons are not lost in autistic brains, so there is nothing that would be “replaced” by such a treatment. And although some forms of autism might include inflammation that could potentially be mitigated, it is unlikely that the degree of benefit that might come from reducing inflammation would be worth the risks of the treatment, which includes intracranial injection of donated material. Unfortunately, we still do not know enough about the specific causes and features of autism to determine if and to what extent stem cell treatments could prove helpful. But we are learning more every day, especially with some of the new technologies and discoveries that have been enabled by stem cell technology.
Some therapies even use tissue from sheep claiming that a pill containing sheep pancreas can migrate to and cure a human pancreas, pills containing sheep brains can help heal human brains. What are your thoughts on those?
For some conditions, there may be a scientific rationale for how a specific drug or treatment could be delivered orally, but this really depends on the underlying biology of the condition, the means by which the drug exerts its effect, and how quickly that drug or substance will be digested, metabolized, or cleared from the body’s circulation. Many drugs that are delivered orally do not reach the brain because of the blood-brain barrier, which serves to isolate and protect the brain from potentially harmful substances in the blood circulation. For such a drug to be effective, it would have to be stable within the body for a period of time, and be something that could exert its effects on the brain either directly or indirectly.
Sheep brain or pancreas (or any other animal tissue consumed) in a pill form would be broken down into basic components immediately by digestion, i.e. amino acids, sugars, much like any other meat or food. Often complex treatments designed to be specifically targeted to the brain are delivered by intra-cranial/intrathecal injection, or by developing special strategies to evade the blood brain barrier, a challenge that is easier said than done. For autism, there is still a lot to be learned regarding how a therapeutic intervention might work to help people, so for now, I would caution against the use of dietary supplements or pills that are not prescribed or recommended by your doctor.
What are the questions parents should ask before signing up for any stem cell therapy
There is some very good advice about this on the both the CIRM and ISSCR websites, including a handbook for patients that includes questions to ask anyone offering you a stem cell treatment, and also some fundamental facts that everyone should know about stem cells. https://www.closerlookatstemcells.org/patient-resources/
What kinds of techniques do we have now that we didn’t have in the past that can help us better understand what is happening in the brain of a child with autism.
We covered this in the online presentation. Some of the technologies discussed include:
– “disease in a dish” models from patient derived stem cells for studying causes of autism
– new ways to make human neurons and other cell types for study
– organoid technology, to create more realistic brain tissues for studying autism
– advances in genomics and sequencing technologies to identify “signatures” of autism to help identify the underlying differences that could lead to a diagnosis
Alysson, you work with things called “brain organoids” explain what those are and could they help us in uncovering clues to the cause of autism and even possible therapies?
We blogged about this work when it was first published and you can read about it on our blog here.