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.
September is National Sickle Cell Awareness Month, a time to refocus our efforts to find new treatments, even a cure, for people with sickle cell disease. Until we get those, CIRM remains committed to doing everything we can to reduce the stigma and bias that surrounds it.
Sickle cell disease (SCD) is a rare, inherited blood disorder in which normally smooth and round red blood cells may become sickle-shaped and harden. These blood cells can clump together and clog up arteries, causing severe and unpredictable bouts of pain, organ damage, vision loss and blindness, strokes and premature death.
There is a cure, a bone marrow transplant from someone who is both a perfect match and doesn’t carry the SCD trait. However, few patients are able to find that perfect match and even if they do the procedure carries risks.
That’s why the California Institute for Regenerative Medicine (CIRM) has invested almost $60 million in 14 projects, including five clinical trials targeting the disease. It’s also why we are partnering with the National Heart, Lung and Blood Institute (NHLBI) in their Cure Sickle Cell Initiative (CureSCi).
As part of the events around National Sickle Cell Awareness Month the NHLBI is launching the Gene Therapy to Reduce All Sickle Pain (GRASP) Trial and hosting a special Journeys in Mental Health Webinar on September 27th.
The GRASP Trial is a Phase 2 trial that will take place at various locations throughout the country. It’s a collaboration between the NHLBI and CIRM. Researchers are testing whether a gene therapy approach can improve or eliminate sickle cell pain episodes.
Shortly after being born, babies stop producing blood containing oxygen-rich fetal hemoglobin and instead produce blood with the adult hemoglobin protein. For children with sickle cell disease, the transition from the fetal to the adult form of hemoglobin marks the onset of anemia and the painful symptoms of the disorder.
Scientists previously discovered that the BCL11A gene helps to control fetal hemoglobin and that decreasing the expression of this gene can increase the amount of fetal hemoglobin while at the same time reducing the amount of sickle hemoglobin in blood. This could result in boosting the production of normal shaped red blood cells with a goal of curing or reducing the severity of sickle cell disease.
The approach used in this trial is similar to a bone marrow transplant, but instead of using donor stem cells, this uses the patient’s own blood stem cells with new genetic information that instructs red blood cells to silence the expression of the BCL11A gene. This approach is still being studied to make sure that it is safe and effective, but it potentially has the advantage of eliminating some of the risks of other therapies.
In this trial, patients will have to spend some time in an inpatient unit as they undergo chemotherapy to kill some bone marrow blood stem cells and create room for the new, gene-modified cells to take root.
The trial is based on a successful pilot/phase 1 study which showed it to be both safe and effective in the initial 10 patients enrolled in the trial.
For more information about the trial, including inclusion/exclusion criteria and trial locations, please visit the CureSCi GRASP trial page.
Nancy Rene, a sickle cell disease patient advocate, says while clinical trials like this are obviously important, there’s another aspect of the treatment of people with the disease that is still too often overlooked.
“As much as I applaud CIRM for the work they are doing to find a therapy or cure for Sickle Cell, I am often dismayed by the huge gulf between research protocols and general medical practice. For every story I hear about promising research, there is often another sad tale about a sickle cell patient receiving inadequate care. This shouldn’t be an either/or proposition. Let’s continue to support ground-breaking research while we expand education and training for medical professionals in evidenced based treatment. I look forward to the day when sickle cell patients receive the kind of treatment they need to lead healthy, pain-free lives.”
With funding support from the California Institute for Regenerative Medicine (CIRM), Cedars-Sinai investigators have developed an investigational therapy using support cells and a protective protein that can be delivered past the blood-brain barrier. This combined stem cell and gene therapy can potentially protect diseased motor neurons in the spinal cord of patients with amyotrophic lateral sclerosis, a fatal neurological disorder known as ALS or Lou Gehrig’s disease.
In the first trial of its kind, the Cedars-Sinai team showed that delivery of this combined treatment is safe in humans. The findings were reported in the peer-reviewed journal Nature Medicine.
What causes ALS?
ALS is a progressive neurodegenerative disease that affects nerve cells in the brain and spinal cord. About 6,000 people are diagnosed with ALS each year in the U.S., and the average survival time is two to five years.
The disease results when the cells in the brain or spinal cord that instruct muscles to move—called motor neurons—die off. People with the disease lose the ability to move their muscles and, over time, the muscles atrophy and people become paralyzed and eventually die. There is no effective therapy for the disease.
Using Stem Cells to Treat ALS
In a news release, senior author Clive Svendsen, PhD, executive director of the Cedars-Sinai Board of Governors Regenerative Medicine Institute, says using stem cells shows lots of promise in treating patients with ALS.
“We were able to show that the engineered stem cell product can be safely transplanted in the human spinal cord. And after a one-time treatment, these cells can survive and produce an important protein for over three years that is known to protect motor neurons that die in ALS,” Svendsen says.
Aimed at preserving leg function in patients with ALS, the engineered cells could pave the way to a therapeutic option for this disease that causes progressive muscle paralysis, robbing people of their ability to move, speak and breathe.
The study used stem cells originally designed in Svendsen’s laboratory to produce a protein called glial cell line-derived neurotrophic factor (GDNF). This protein can promote the survival of motor neurons, which are the cells that pass signals from the brain or spinal cord to a muscle to enable movement.
In patients with ALS, diseased glial cells can become less supportive of motor neurons, and these motor neurons progressively degenerate, causing paralysis.
By transplanting the engineered protein-producing stem cells in the central nervous system, where the compromised motor neurons are located, these stem cells can turn into new supportive glial cells and release the protective protein GDNF, which together helps the motor neurons stay alive.
Ensuring Safety in the Trial
The primary goal of the trial was to ensure that delivering the cells releasing GDNF to the spinal cord did not have any safety issues or negative effects on leg function.
In this trial, none of the 18 patients treated with the therapy—developed by Cedars-Sinai scientists and funded by CIRM—had serious side effects after the transplantation, according to the data.
Because patients with ALS usually lose strength in both legs at a similar rate, investigators transplanted the stem cell-gene product into only one side of the spinal cord so that the therapeutic effect on the treated leg could be directly compared to the untreated leg.
After the transplantation, patients were followed for a year so the team could measure the strength in the treated and untreated legs. The goal of the trial was to test for safety, which was confirmed, as there was no negative effect of the cell transplant on muscle strength in the treated leg compared to the untreated leg.
Investigators expect to start a new study with more patients soon. They will be targeting lower in the spinal cord and enrolling patients at an earlier stage of the disease to increase the chances of seeing effects of the cells on the progression of ALS.
“We are very grateful to all the participants in the study,” said Svendsen. “ALS is a very tough disease to treat, and this research gives us hope that we are getting closer to finding ways to slow down this disease.”
The Cedars-Sinai team is also using the GDNF-secreting stem cells in another CIRM-funded clinical trial for ALS, transplanting the cells into a specific brain region, called the motor cortex that controls the initiation of movement in the hand. The clinical trial is also funded by CIRM.
The California Institute for Regenerative Medicine (CIRM) remains committed to funding research and clinical trials to treat ALS. To date, CIRM has provided $93 million in funding for research to treat ALS.
Read the original source release of the study here.
Growing up Veronica McDougall thought everyone saw the world the way she did; blurry, slightly out-of-focus and with tunnel vision. As she got older her sight got worse and even the strongest prescription glasses didn’t help. When she was 15 her brother tried teaching her to drive. One night she got into the driver’s seat to practice and told him she couldn’t see anything. Everything was just black. After that she stopped driving.
Veronica says high school was really hard for her, but she managed to graduate and go to community college. As her vision deteriorated, she found it was increasingly hard to read the course work and impossible to see the assignments on the blackboard. Veronica says she was lucky to have some really supportive teachers — including the now First Lady Jill Biden — but eventually she had to drop out.
Getting a diagnosis
When she was 24, she went to see a specialist who told her she had retinitis pigmentosa, a rare degenerative condition that would eventually leave her legally blind. She says it felt like a death sentence. “All of my dreams of becoming a nurse, of getting married, of having children, of traveling – it all just shattered in that moment.”
Veronica says she went from being a happy, positive person to an angry depressed one. She woke up each morning terrified, wondering, “Is this the day I go blind?”
Then her mother learned about a CIRM-funded clinical trial with a company called jCyte. Veronica applied to be part of it, was accepted and was given an injection of stem cells in her left eye. She says over the course of a few weeks, her vision steadily improved.
“About a month after treatment, I was riding in the car with my mom and suddenly, I realized I could see her out of the corner of my eye while looking straight ahead. That had never, ever happened to me before. Because, I had been losing my peripheral vision at a young age without realizing that until up to that point, I had never had that experience.”
A second chance at life
She went back to college, threw herself into her studies, started hiking and being more active. She says it was as if she was reborn. But in her senior year, just as she was getting close to finishing her degree, her vision began to deteriorate again. Fortunately, she was able to take part in a second clinical trial, and this time her vision came back stronger than ever.
“I’m so grateful to the researchers who gave me my sight back with the treatment they have worked their entire lives to develop. I am forever grateful for the two opportunities to even receive these two injections and to be a part of an amazing experience to see again. I feel so blessed! Thank you for giving me my life back.”
And in getting her life back, Veronica had a chance to give life. When she was at college she met and starting dating Robert, the man who was to become her partner. They now have a little boy, Elliott.
As for the future, Veronica hopes to get a second stem cell therapy to improve her vision even further. Veronica’s two treatments were in her left eye. She is hoping that the Food and Drug Administration will one day soon approve jCyte’s therapy, so that she can get the treatment in her right eye. Then, she says, she’ll be able to see the world as the rest of us can.
Explaining science is hard. Explaining stem cells, which have their very own unique complexities, can be even more of a challenge, especially when communicating with a non-scientific audience.
That’s why when we received this blog submission from a CIRM SPARK Program intern through UCSF’s High School Intern Program (HIP) explaining stem cells in a simple, straightforward way using Legos, we knew we had to share it with our readers.
Before we share the intern’s brilliant explanation of stem cells, here’s how the California Institute for Regenerative Medicine (CIRM) defines stem cells. These and other key terms can be found on our website:
The first thing to know about stem cells is that there is not just one kind. In fact, there are many different types of stem cells, each with very different potential to treat disease. There are various types of stem cells, including pluripotent, embryonic, adult, and iPSC (induced pluripotent stem cell).
Stem cells also have the potential to become other kinds of cells in the body. For example, embryonic stem cells can become many other kinds of cells, whereas adult stem cells, such as in fat, can only become bone or cartilage.
Now, the fun part! Here’s what the student shared in their prize-winning SPARK Program blog submission.
If someone were to ask me what stem cells are in a simple and perhaps figurative way now, I would say that stem cells are just like Legos. Legos are special building-blocks that are in a blank or default-like state, but can be something greater and unique on its own later on.
Similarly, stem cells are called “unspecialized cells” because they are yet to be “specialized” or become a certain type of cell. They can be a blood, brain, heart, and basically all types of cells respectively, with little to no exceptions. Moreover, not all Legos are built the same. Some can be regular block-shaped, while some can be circular or even triangular. Therefore, this limits Legos’ abilities to a certain degree. Similarly, not all stem cells are necessarily the same.
With just the right amount and type of Legos, you can easily assemble and build a house, a car, or whatever you could possibly think about. Similarly, the possibilities are endless with stem cells as well, which is why it’s truly a promising and key aspect in regenerative medicine today.
Bravo! In addition to creating a unique way of explaining stem cells during their internship, the student also learned how to differentiate the different types and sources of stem cells from one another through hands-on experience at a world-renowned institution.
The student added, “My newly-found interest in regenerative medicine and stem cells is definitely something that I’m looking forward to with great passion and knowledge moving forward.”
This summer—as well as year round—the California Institute for Regenerative Medicine (CIRM) will highlight blog submissions, photos, and other fun content from our SPARK Program.
SPARK—also known as the Summer Program to Accelerate Regenerative Medicine Knowledge—gives high school students a chance to spend their summer working in a world class stem cell research facility here in California. At the end of their internship, they write about their experiences and what they learned.
As always, we received many wonderful submissions from the students, so choosing a winner was particularly tough. In the end we chose two winners. The first blog—which you can read below—was submitted by Saranya Anandakumar, who interned at Sanford Burnham Prebys in La Jolla.
The second winning submission was authored by John Casilao, who interned at UCSF. The blog will also be shared on The Stem Cellar this week.
Check out Saranya’s winning blog submission below and be sure to follow the blog for more updates from CIRM’s SPARK Program.
Submitted by Saranya Anandakumar
2022 SPARK Program Intern at Sanford Burnham Prebys
My whole life I’ve been indecisive, which I think is fair. I mean, think about it. If the multiverse theory is coupled with the butterfly effect then the difference between a vanilla and strawberry ice cream could mean the difference between my continued life or my sudden death.
So if I can’t even choose which cereal to eat in the morning, what in the world makes my counselor think I can decide what career I want to pursue in the future? What’s worse is while an ice cream cone only lasts about ten or fifteen minutes in the beaming hot summer Sun before wasting away, my occupational choice, my major, and my degree, they’ll stay with me forever if not for at least ten or so years. So why not give a six-week free trial a shot? That way of thinking, dear reader, is precisely how I ended up in CIRM’s SPARK Program.
Hi, my name is Saranya Anandakumar. I love oceanography and glaciology as much as I love law and psychiatry, but the medical field has always had a special place in my heart. That’s how I took the first step of applying for this internship.
To give a brief summary, my grandma had a stroke and pneumonia and has been bedridden since because a doctor gave her the incorrect dose of medication (according to medical staff she should have been dead). My mom has struggled with chronic pain, migraines, memory issues, and high blood pressure for years, and my entire family struggles with severe anxiety and depression (plus the occasional eating disorder).
Of course, I have a breathing disorder and struggle with migraines. I also have an extremely weak immune system to the point where I’m ill eight months of the year. Needless to say, emergency room and ICU visits have become the norm, so much that the nurses and I are on a first-name basis.
But, enough about my glamorous history, and more about my experience with the internship. As I established earlier, I am certain about nothing in my life, which is why it should speak volumes to you when I say I now know that I want to major in immunology and minor in neuroscience.
Still, a little voice inside my head cries, “Oh, what if this is the best lab you’ll ever be in?! What if you think the field is better than it really will be?!” A valid concern. I’m sure Dr. Blaho is the only former Trombone player and drum major I will ever work under, and she’s certainly the funniest. I doubt anyone will have the dad jokes Josh does or the endearing laugh and interesting input Yosiris does.
However, my time at Sanford Burnham Prebys still left me with more than that. I loved walking in every day. Every lecture on oligodendrocytes and microglia had me entranced. Every western blot or stem cell experiment left me all giddy inside. Don’t even get me started on looking at human blood under a microscope! It felt like falling in love and the best part was it didn’t matter what it was as long as I was learning something new.
I was always scared of life after college, but I thought it was because I was scared of committing to one career for the rest of my life. And though that was certainly part of it, I think I was afraid of living my life without learning anymore. So bio research is perfect for me because it’s impossible to not learn even if you try.
We had a wonderful time meeting so many energetic and enthusiastic high school students at the 2022 SPARK Program annual conference hosted by UCSF at the MLK Research Building. The SPARK program is one of the California Institute for Regenerative Medicine’s (CIRM) many programs dedicated to building a diverse and highly-skilled workforce to support the growing regenerative medicine economy right here in California.
Held in-person for the first time since 2019, the event hosted students and program directors from all over California, allowing them the opportunity to share their research through oral and poster presentations. This year, students also attended talks about new approaches to sickle cell disease curative therapies, anti-racism in STEM, and patient advocacy.
The SPARK Program—also known as the Summer Program to Accelerate Regenerative Medicine Knowledge—provides California high school students with summer research internships at leading stem cell institutes in California. To date, there have been 530 SPARK alumni, and another 110 high school interns are completing their training this summer.
The SPARK program specifically selects students who represent the diversity of California’s population, particularly those who might not otherwise have opportunities to take part in research internships due to socioeconomic constraints.
“I really enjoyed being a part of this program, and I feel like I understand so much better what it’s like to be a researcher,” said Brighton C., a student in the SPARK program at Charles R. Drew University of Medicine and Science (pictured below). “I also feel more confident in the subject of stem cells and I might want to dedicate my future to it.”
We’ll be sharing more stories from CIRM’s SPARK Program throughout the year, including blog submissions from students that summarize their summer experiences. Stay tuned for more and be sure to follow CIRM on Instagram, where we will share more photos and fun content created by the students.
There are currently 11 active SPARK programs throughout California, each with its own eligibility criteria and application process. If you are interested in learning more, please visit this web page for more details about each program. If you have questions about CIRM’s education programs, please email Dr. Kelly Shepard at firstname.lastname@example.org.
Thank you to UCSF for hosting the event, and to all the SPARK program directors for supporting this year’s bright interns!
Check out some of the photos from this year’s SPARK conference below.
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.