Investing in a stem cell treatment for Hurler syndrome

The California Institute for Regenerative Medicine (CIRM) awarded $5,444,353 to Dr. Natalia Gomez-Ospina and her team at Stanford University for a late-stage preclinical program targeting Severe Mucopolysaccharidosis type 1, also known as Hurler syndrome. This is an inherited condition caused by a faulty gene.

Children with Hurler syndrome lack an enzyme that the body needs to digest sugar. As a result, undigested sugar molecules build up in the body, causing progressive damage to the brain, heart, and other organs.

There are no signs or symptoms of the condition at birth, although some have a soft out-pouching around the belly-button or lower abdomen. Those with severe MPS I generally begin to show other signs and symptoms of the disorder within the first year of life. There is no effective treatment and life expectancy for many of these children is only around ten years.

Dr. Gomez-Ospina will use the patient’s own blood stem cells that have been genetically edited to restore the missing enzyme. The goal of this preclinical program is to show the team can manufacture the needed cells, to complete safety studies and to apply to the US Food and Drug Administration for an Investigational New Drug (IND), the authorization needed to begin a clinical trial in people.

“The funding will pave the way for trials in people to realize a more effective therapy for this devastating disease,” Gomez-Ospina said. “We will also generate safety and toxicity data that could facilitate the application of our genome editing platform to other genetic disorders for which a significant unmet need still exists.”

Advancing cutting-edge treatment to improve kidney transplantation in children

Stanford physician-scientist Alice Bertaina, MD, PhD, associate professor of pediatrics has received about $18 million from the California Institute for Regenerative Medicine (CIRM) for a clinical trial to allow kidney transplantation without the need for long-term immunosuppression.

Dr. Bertaina and her team at Stanford University were awarded $11,998,188 to test an approach that uses combined blood stem cell (HSC) and kidney transplantation with the goal to improve outcomes with kidney transplantation in children. This approach seeks to improve on the blood stem cell preparation through an immune-based purification process.

In this approach, the donor HSC are transplanted into the patient in order to prepare for the acceptance of the donor kidney once transplanted. Donor HSC give rise to cells and conditions that re-train the immune system to accept the kidney. This creates a “tolerance” to the transplanted kidney providing the opportunity to avoid long-term need for medications that suppress the immune system.

Pre-clinical data support the idea that this approach could enable the patient to stop taking any immunosuppression medications which have significant long-term risks.

Funding development of a vaccine for acute myelogenous leukemia (AML)

Dr. Karin Gaensler. Photo credit: Steve Babuljak/UCSF

Adult acute myelogenous leukemia—also known as acute myeloid leukemia (AML)—is a blood cancer in which the bone marrow makes a large number of abnormal blood cells. 

About 20,000 new cases of AML are diagnosed each year in the US with a 5-year survival rate of around 29%. In 2022, there were nearly 12,000 deaths from AML. Many AML patients—a majority of which are over 60 years old—relapse after treatment. Blood stem cell transplant can be curative, but many older patients do not qualify, showing that there is a significant unmet medical need in treating AML. 

That’s why the California Institute for Regenerative Medicine (CIRM) awarded $6,000,000 to Dr. Karin Gaensler at the University of California, San Francisco (UCSF) to support development of a safe and effective vaccine for the blood cancer AML to improve relapse-free survival. 

To develop the cancer vaccine, Dr. Gaensler and her team will engineer the patient’s blood stem cells to maximize stimulation of leukemia-specific killing activity and reintroduce engineered cells back to the patient to target and kill residual leukemia stem cells.  

This approach holds the potential for long-term effectiveness as it targets both AML blasts and leukemic stem cells that are often the source of relapse.  

This award is a continuation of a previous CIRM grant that will support the manufacture of the vaccine and the completion of late-stage testing and preparation needed to apply to the US Food and Drug Administration (FDA) for permission to begin a clinical trial. 

The Most Read Stem Cellar Blog Posts of 2022

This year was a momentous one for the California Institute for Regenerative Medicine (CIRM). You can read some of our achievements in our 2021-2022 annual report.  

As always, 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. More than 100,000 blog visitors followed along throughout the year!  

In case you missed them, here’s a recap of our most popular blogs of 2022. We look forward to covering even more topics in 2023 and send a sincere thank you to our wonderful Stem Cellar readers for tuning in!   


In Memory of Kevin McCormack 

We cannot close out the year without honoring our dear friend and colleague Kevin McCormack, who passed away suddenly in December. Kevin was CIRM’s Director of Patient Advocacy and loved writing for The Stem Cellar. He did a wonderful job in translating complex science for the general public and was a great mentor to the CIRM team. Many of his closest friends and colleagues wrote memories about him, and we compiled them in this blog post honoring his life and dedication to CIRM and patients everywhere.  

How stem cells helped Veronica fight retinitis pigmentosa and regain her vision 

We shared the story of Veronica McDougall, who thought everyone saw the world the way she did: blurry, slightly out-of-focus and with tunnel vision. 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. Click through to read about her experience participating in a CIRM-funded clinical trial with a company called jCyte

Smoking marijuana could be bad for your heart, but there is an unusual remedy 

Millions of Americans use marijuana for medical reasons, such as reducing anxiety or helping ease the side effects of cancer therapy. Millions more turn to it for recreational reasons, saying it helps them relax. Now a new study says those who smoke marijuana regularly might be putting themselves at increased risk of heart disease and heart attack. Check out this blog to learn how a team at Stanford Medicine used the iPSC method to create human endothelial cells and, in the lab, found that THC appeared to promote inflammation in the cells. 

A pioneering couple uproot their lives to help their baby 

This year, we shared some encouraging news about a CIRM-funded stem cell clinical trial for spina bifida at UC Davis Health. Spina bifida is a birth defect that occurs when the spine and spinal cord don’t form properly and can result in life-long walking and mobility problems for the child, even paralysis. This blog told the story of parents Michelle Johnson and Jeff Maginnis, who learned 20 weeks into the pregnancy that the fetus had spina bifida. Read the whole story to learn about their experience and the status of their baby Tobi.  


And that wraps up The Stem Cellar’s top blog posts of 2022! 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.

Finding a treatment for Tay-Sachs disease

The California Institute for Regenerative Medicine (CIRM) has awarded $4,048,253 to Dr. Joseph Anderson and his team at UC Davis to develop a blood stem cell gene therapy for the treatment of Tay-Sachs disease.  

Tay-Sachs disease is a rare genetic disorder where a deficiency in the Hex A gene results in excessive accumulation of certain fats in the brain and nerve cells and causes progressive dysfunction.  

There are several forms of Tay-Sachs disease, including an infant, juvenile, and adult forms. Over a hundred mutations in the disease-causing Hex A gene have been identified that result in enzyme disfunction. There are currently no effective therapies or cures for Tay-Sachs. 

Illustration by Kateryna Kon

The UC Davis team will genetically modify the patient’s own blood stem cells to restore the Hex A enzyme that is missing in the disease.  

The goal is to complete safety studies and to apply to the US Food and Drug Administration for an Investigational New Drug (IND), the authorization needed to begin a clinical trial in people.  

“The successful development of this therapy will not only help patients with Tay-Sachs but will demonstrate the use case of this therapeutic approach for other monogenic neurodegenerative diseases,” the UC Davis team said. 

This work is a continuation of a CIRM grant that the team received. 

CIRM funds clinical trial to make cancer therapy safer, less toxic

Blood stem cell transplantation following high dose chemotherapy is standard of care and potentially curative for aggressive forms of lymphoma. However, this treatment regimen is limited by severe toxicity and life-threatening complications due to delayed recovery of the blood system and vascular related damage of multiple organs.

Today the governing Board of the California Institute for Regenerative Medicine (CIRM) funded a Phase 3 clinical trial to support development of a safer, more tolerable alternative.

This brings the number of clinical trials funded by CIRM to 86.

The Board awarded $15,000,000 to Dr. Paul Finnegan and Angiocrine Bioscience to test AB-205, human endothelial cells engineered to express a pro-survival factor.

Prior data suggest that, in the setting of chemotherapy and stem cell transplantation, AB-205 cell therapy can accelerate the recovery of the blood system and protects from toxicity by enhancing the recovery from vascular damage. AB-205 is being studied in a Phase 3 trial in adults with lymphoma undergoing high-dose chemotherapy and autologous blood stem cell transplant.

“If successful, this approach can overcome hurdles to the success of chemotherapy and blood stem cell transplantation for the treatment of advanced blood cancer,” says Dr. Maria T. Millan, President and CEO of CIRM. “This Phase 3 trial is the culmination of preclinical research and the initial clinical trial previously funded by CIRM.”

Lymphoma is the most common blood cancer and one of the most common cancers in the United States, accounting for about 4% of all cancers according to the American Cancer Society and the 6th most commonly diagnosed cancer among men and women in California.  It is estimated that there will be 89,010 new cases of lymphoma and 21,170 lymphoma related deaths in the US in 2022 alone.  In California, it is estimated that there will be over 9,250 new cases of lymphoma with over 2,100 deaths.

“Angiocrine Bioscience is honored to be awarded this grant from CIRM to support our AB-205 Phase 3 trial,” commented Angiocrine CEO Dr. Paul Finnegan. “CIRM has been an instrumental partner in our development of AB-205, a novel therapeutic that acts on the patients’ endogenous stem cell niches. The grant award will considerably aid in our effort to bring forth a solution to the unmet need of transplant-related complications.”

Update on spinal cord injury patient enrolled in CIRM-funded stem cell clinical trial

Jake Javier and his parents at Duke University

A spinal cord injury (SCI) is devastating, changing a person’s life in an instant. Every year, around the world, between 250,000 and 500,000 people suffer a spinal cord injury. Most of these are caused by trauma to the spinal column, thereby affecting the spinal cord’s ability to send and receive messages from the brain to the body’s systems that control sensory, motor and autonomic function below the level of injury.

Currently, there is nothing that completely reverses SCI damage and most treatment is aimed at rehabilitation and empowering patients to lead as normal a life as possible under the circumstances. Improved treatment options are necessary both to improve patients’ overall quality of life, and to reduce associated healthcare costs.

In 2010, the Geron trial became not only the first clinical trial to be funded by the California Institute for Regenerative Medicine (CIRM), but the first clinical trial in the world using embryonic stem cells.

By 2014, Asterias Biotherapeutics (now Lineage Cell Therapeutics Inc.), acquired the cell therapy assets of Geron and launched its Phase 1/2a clinical trial with the goal of determining the safety of the therapy and the optimal dose of cells to transplant into patients.

In 2016, Jake Javier became the fifth patient to participate in the revived Asterias trial. Regular readers of our blog will remember that Jake is the young man who broke his neck the day before he graduated high school, leaving him paralyzed from the upper chest down.

After enrolling in the CIRM-funded Asterias clinical trial, and receiving a transplant of ten million stem cells, Jake regained enough use of his arms and hands to be able to go to Cal Poly and start his life over.

This video highlights the struggles and challenges he faced in his first year, and his extraordinary spirit in overcoming them.

Video courtesy of Matt Yoon and his team at Cal Poly

Today, Jake is set to graduate from Duke University with his master’s degree in Biomedical Engineering, with plans to help those impacted by neurological injuries or disease.

Watch the video below to learn more about Jake’s personal perspective on his clinical trial participation, the OPC1 clinical study, his future plans and his message to the SCI community.

Video courtesy of Lineage Cell Therapeutics Inc.

Lab-made retinas offer a new approach to battling vision loss

Age-related macular degeneration (AMD) is the leading cause of vision loss in the elderly. Now, new research using 3D organoid models of the eye has uncovered clues as to what happens in AMD, and how to stop it. 

In AMD, a person loses their central vision because the light sensitive cells in the macula, a part of the retina, are damaged or destroyed. This impacts a person’s ability to see fine details, recognize faces or read small print, and means they can no longer drive. 

AMD causes blurry and distorted vision 

No one is quite sure what causes AMD, but in a study in the journal Nature Communications, German researchers used miniature human retina organoids to get some clues.  

Building a better model for research

Organoids are 3D models made from human cells that are grown in the lab. Because they have some of the characteristics of a human organ—in this case the retina—they help researchers better understand what is happening in the AMD-affected eye. 

In this study they found that photoreceptors, the light sensitive cells at the back of the retina, were missing but there was no sign of dead cells in the organoid. This led them to suspect that something called cell extrusion was at play.  

Cell extrusion is where a cell exports or sends large particles outside the cell. In this case it appeared that something was causing these photoreceptors to be extruded, leading to the impaired visual ability.  

In a news release Mark Karl, one of the authors of the study, said, “This was the starting point for our research project: we observed that photoreceptors are lost, but we could not detect any cell death in the retina. Half of all photoreceptors disappeared from the retinal organoid within ten days, but obviously they did not die in the retina. That made us curious.” 

Using snakes to fight AMD 

Further research identified two proteins that appeared to play a key role in the process, triggering the degeneration of the retinal organoid. They also tested a potential therapy to see if they could stop the process and save the photoreceptors. The therapy they tried, a snake venom, not only stopped the photoreceptors from being ejected, but it also prevented further damage to the retinal cells. 

Karl says this is the starting point for the next step in the research. “This gives hope for the development of future preventive and therapeutic treatments for complex neurodegenerative diseases such as AMD.” 

CIRM’s fight against blindness 

The California Institute for Regenerative Medicine (CIRM) has funded six clinical trials targeting vision loss, including one for AMD. We recently interviewed Dr. Dennis Clegg, one of the team trying to develop a treatment for AMD and he talked about the encouraging results they have seen so far. You can hear that interview on our podcast “Talking ‘Bout (re)Generation.” 

Bubble baby treatment cleared to restart clinical trial

Evie Vaccaro: Photo courtesy Nancy Ramos

Three families battling a life-threatening immune disorder got some great news last week. A clinical trial that could save the life of their child has once again been given the go-ahead by the US Food and Drug Administration (FDA).

The clinical trial is the work of UCLA’s Dr. Don Kohn, and was strongly supported by CIRM. It is targeting ADA-SCID, a condition where the child is born without a functioning immune system so even a simple infection could prove fatal. In the past they were called “bubble babies” because some had been placed inside sterile plastic bubbles to protect them from germs.

Dr. Kohn’s approach – using the patient’s own blood stem cells, modified in the lab to correct the genetic mutation that causes the problem – had shown itself to be amazingly effective.  In a study in the prestigious New England Journal of Medicine, the researchers showed that of 50 patients treated all had done well and 97 percent were considered cured.

UCLA licensed the therapy to Orchard Therapeutics, who planned to complete the testing needed to apply for permission to make it more widely available. But Orchard ran into problems and shelved the therapy.

After lengthy negotiations Orchard returned the therapy to UCLA last year and now the FDA has given clearance for UCLA to resume treating patients. That is expected to start early next year using CIRM funds left over when Orchard halted its work.

One of the people who played a big role in helping persuade Orchard to return the therapy to UCLA is Alysia Vaccaro. She is the mother of Evie, a child born with ADA-SCID who was cured by Dr. Kohn and his team and is now a thriving 9 year old.

You can watch an interview we did with Alysia about the impact this research has had on her family, and how important it is for other families with ADA-SCID kids.

High school SPARK intern presents stem cell research to academic audience 

Earlier this year, CIRM welcomed many energetic and enthusiastic high school students at the 2022 SPARK Program annual conference in Oakland. 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.   

At the SPARK conference, a handful of students presented the stem cell research they did over the summer. It was a great opportunity to share their experiences as well as findings to their high school peers. 

Just recently, Simran Ovalekar—a 2022 SPARK program intern—had the unique opportunity to share her research and findings with a wider audience, including undergraduate and PhD students at STEM Shadow Day in San Diego. The event aims to provide college prep students from San Diego and Imperial Valley counties with a unique experience to witness the “real world” of work in an engineering or scientific environment. 

“At first I was nervous because I understood that I would be presenting not only in front of high school students, but also undergraduates and PhD candidates,” Simran says. “After reviewing my research, I felt solid and excited to present. I absolutely loved working in the lab so I knew all I had to do was be myself and show my enthusiasm.”

During the SPARK summer internship, Simran joined the Sacco Lab to study Duchenne Muscular Dystrophy (DMD) and how stem cells can be used to provide treatment. DMD is a progressive muscle wasting disorder with life expectancy of approximately age 20. There are around 17,000 people, the vast majority of them boys, diagnosed with DMD in the US

Dr. Sacco’s lab—which has also received CIRM funding—is researching ways to generate healthy adult muscle stem cells using the patient’s own cells to generate healthy skeletal muscle. 

For Simran, conducting research for DMD was personal, as her sister was born with a defect affecting the heart.  

“When I began this program, I had a superficial understanding of what a stem cell was. Now, however, I am amazed at the possibilities stem cells provide, and with certainty, can say stem cells are the future of medicine.” 

After her presentation at STEM Shadow Day, Simran says she received a positive response from attendees and was reminded why she loves science and of her passion for pursuing a career in stem cell research.  

“I am looking forward to continue skeletal stem cell research and am even open to experimenting with other avenues of molecular medicine,” Simran says. “I am eager to have the opportunity to pursue the hands-on research I enjoyed this past summer.” 


CIRM has also funded a clinical trial for people with DMD. We blogged about that work and how the impact it is having on some people’s lives.