California agency invests $4 million in stem cell treatment for Parkinson’s Disease

The California Institute for Regenerative Medicine (CIRM) is investing $4 million in a late-stage preclinical project by Ryne Bio aiming to improve treatment for Idiopathic Parkinson’s disease (PD).

PD is characterized by a loss of dopamine producing neurons that result in motor symptoms, such as dyskinesias (involuntary, erratic, writhing movements of the face, arms, legs or trunk) and non-motor effects such as dementia, depression and sleep disorders.

PD is the second-most common neurodegenerative disease after Alzheimer’s disease affecting approximately 1 million people in the U.S. In California, it is estimated that 116,900 people live with PD, representing the highest number of people with the disease in the country.

At its early stages, PD can be treated with medication such as Levodopa to treat symptoms but these become less effective as the disease progresses.

The proposed stem cell therapy in this project offers the potential to restore dopamine neurons, which play a role in many important body functions, including movement and memory.

Investigators at Ryne Bio are aiming to deliver dopamine producing cells to replace the lost neurons to the brain of Parkinson’s disease patients to restore/improve motor function.

The current grant is being funded to conduct Investigational New Drug (IND) enabling, nonclinical safety studies per the US Food and Drug Administration (FDA) Guidance. The IND is the authorization needed to begin a clinical trial in Parkinson’s patients.

CIRM has a vested interest in seeing this therapy succeed. To date, CIRM has invested more than $59 million in helping research for Parkinson’s disease progress from a basic or Discovery level through clinical trials.

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.”

Three women with ties to CIRM featured in 2022 Women in Biopharma list 

Endpoints News released its 2022 Women in Biopharma list, which recognizes 20 of the top women leading biopharma research and development (R&D).  

This year, the publication received more than 500 entries and selected 20 women “who have blazed trails and are still promising to reshape biopharma R&D for years to come.” 

There are many amazing finalists featured this year, but three in particular stood out for their ties to the California Institute for Regenerative Medicine (CIRM). Those three are:  

Jennifer Gordon, Ph.D. — Senior Vice President of Research and Development at Excision BioTherapeutics 

Dr. Jennifer Gordon and the team at Excision Bio Therapeutics have developed a therapeutic candidate called EBT-101. CIRM is funding a clinical trial to test EBT-101 in patients with HIV. 

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 of the treatment is to eliminate or sufficiently reduce the hidden reservoirs of virus in the body to the point where the individual is effectively cured. 

Barbara Wirostko — Co-founder and CMO at Qlaris Bio 

Barbara Wirostko is the co-founder and CMO at Qlaris Bio, a clinical stage biotech company committed to developing therapies for patients suffering from serious and debilitating ophthalmic diseases.  

In addition to her work there, Barbara is a member of CIRM’s Grants Working Group (GWG), which is responsible for evaluating the scientific merit of all applications submitted to CIRM and provides funding recommendations to the CIRM board.  

In the Endpoints News profile, Wirostko shares that she was inspired by her father, also an ophthalmologist, and his desire to help people. 

“I think that was the other thing that really drew me to ophthalmology — is that you were able to work with patients, make a difference in people’s lives, also have a surgical as well as a medical aspect, practicing medicine, and then also have a family,” she said. 

Dr. Lili Yang – UCLA associate professor, Co-founder of Appia Bio and Immune Design 

We’ve written about Dr. Lili Yang’s work on the Stem Cellar blog.  

Dr. Yang at UCLA was recently awarded $1.4 million by CIRM to develop an off-the-shelf cell therapy for ovarian cancer, which causes more deaths than any other cancer of the female reproductive system. 

With support from several CIRM grants, Dr. Yang has developed a platform that can use healthy donor blood stem cells to produce clinical scalable “off-the-shelf” iNKT cells. That has led to the creation of start-up company Appia Bio, and talks with the FDA about testing a series of iNKT cell products in clinical trials. 

“I have this dream that cell therapy can become off-the-shelf, and how this would really help all cancer patients in need. The current cancer cell therapy requires treating patients one-by-one, resulting in a steep price that is hard to afford,” Dr. Yang says.  

“Not everyone lives near a hospital capable of handling such a personalized therapy or can afford such a steep price. If we can make this therapy with centralized manufacturing, pre-quality controlled and ready for wide use then we don’t need to worry about the gender or age or location of the patient.” 


CIRM congratulates all the extraordinary women featured in the Endpoints News 2022 Women in Biopharma list. To see all the finalists, read the official announcement here or visit the Endpoints News website.  

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.  

 

Tratando malformaciones congénitas antes del nacimiento 

El bebé, Tobi recibió un tratamiento de células madre, financiado por el CIRM, mientras aún estaba en el útero. To read this blog in English, click here.

Michelle y Jeff se llenaron de felicidad cuando se enteraron de que iban a tener un bebé.  

Luego, un examen de ultrasonido a las 20 semanas del embarazo reveló que el feto tenía espina bífida, una malformación congénita que ocurre cuando la columna vertebral y la médula espinal no se forman de manera adecuada. La espina bífida puede causar parálisis y otras complicaciones serias.   

Se derivó a la pareja a un ensayo clínico en la Universidad de California, Davis, que lleva a cabo la Dra. Diana Farmer, cirujana fetal y neonatal reconocida a nivel internacional, y su colega, el Dr. Aijun Wang.  

En este ensayo clínico, que se basó en una previa investigación financiada por el CIRM, se repara el defecto espinal aplicando células madre de una placenta donada, las cuales se insertan en una estructura sintética y se aplican al defecto de la médula espinal mientras el bebé se encuentra todavía en el útero.   

El hijo de Michelle y Jeff, Tobi, fue el segundo paciente que recibió este tratamiento. Michelle dijo que la cirugía fue difícil, pero el nacimiento de su bebé valió la pena.  

“Cuando lo abrazamos por primera vez dijimos, ‘No puedo creer que hayamos hecho esto. Lo logramos. Lo hicimos sin saber si funcionaría’.”   

A los tres meses, el progreso de Tobi parece promisorio. Jeff y Michelle saben que pueden surgir problemas más adelante, pero por ahora se sienten agradecidos de haber formado parte de este ensayo.

To read this blog in English, click here.

Study could pave the way in reducing decline in muscle strength as people age 

A study by Stanford Medicine researchers in older mice may lead to treatments that help seniors regain muscle strength lost to aging.

Muscle stem cells—which are activated in response to muscle injury to regenerate damaged muscle tissue—lose their potency with age. A study from the National Health and Nutrition Examination Survey showed that five percent of adults aged 60 and over had weak muscle strength, and thirteen percent had intermediate muscle strength. 

Now, researchers at Stanford Medicine are seeing that old mice regain the leg muscle strength of younger animals after receiving an antibody treatment that targets a pathway mediated by a molecule called CD47.  

The study was published in Cell Stem Cell and is co-funded by the California Institute for Regenerative Medicine (CIRM).  

A Closer Look at CD47 

CD47 is a protein found on the surface of many cells in the body. Billed as the “don’t eat me” molecule, it is better known as a target for cancer immunotherapy. It’s common on the surface of many cancer cells and protects them from immune cells that patrol the body looking for dysfunctional or abnormal cells.  

Stanford researchers are finding that old muscle stem cells may use a similar approach to avoid being targeted by the immune system. 

It’s been difficult to determine why muscle stem cells lose their ability to divide rapidly in response to injury or exercise as they age. Dr. Ermelinda Porpiglia, the lead author of the study, used a technique called “single-cell mass cytometry” to study mouse muscle stem cells.  

Using the technique, Porpiglia focused on CD47, and found that the molecule was found at high levels on the surface of some muscle stem cells in older mice, but at lower levels in younger animals. Porpiglia also found that high levels of CD47 on the surface of muscle stem cells correlate with a decrease in their function.   

“This finding was unexpected because we primarily think of CD47 as an immune regulator,” Porpiglia said. “But it makes sense that, much like cancer cells, aged stem cells might be using CD47 to escape the immune system.” 

Testing an Antibody 

Further investigation revealed that a molecule called thrombospondin, which binds to CD47 on the surface of the muscle stem cells, suppresses the muscle stem cells’ activity.  

Porpiglia showed that an antibody that recognizes thrombospondin and blocks its ability to bind to CD47 dramatically affected the function of muscle stem cells. Cells from older animals divided more robustly when growing in a laboratory dish in the presence of the antibody, and when the antibody was injected into the leg muscles of old mice the animals developed bigger and stronger leg muscles than control animals.  

When given prior to injury, the antibody helped the aged animals recover in ways similar to younger mice. 

Porpiglia said, “We are hopeful that it might one day be possible to inject an antibody to thrombospondin at specific sites in the body to regenerate muscle in older people or to counteract functional problems due to disease or surgery.” 

These results are significant because they could one day make it possible to boost muscle recovery in humans after surgery and reduce the decline in muscle strength as people age, but researchers say more work is needed.  

“Rejuvenating the muscle stem cell population in older mice led to a significant increase in strength,” said Dr. Helen Blau, a senior author of the study. “This is a localized treatment that could be useful in many clinical settings, although more work needs to be done to determine whether this approach will be safe and effective in humans.” 

CIRM has previously funded work with researchers using CD47 that led to clinical trials targeting cancer. You can read about that work here and here. That work led to the creation of a company, Forty Seven Inc, which was eventually bought by Gilead for $4.9 billion.  

Read the original release by Krista Conger on the Stanford Medicine website. 

Apply Now for New Manufacturing Funding Opportunity

The California Institute for Regenerative Medicine (CIRM) has set goals through its five-year strategic plan to continue to deliver the full potential of regenerative medicine to the people of California and around the world. 

One of those goals is to overcome manufacturing hurdles for the delivery of regenerative medicine therapies by building a public-private manufacturing partnership network. 

This is essential because the field needs to create standardized manufacturing processes to transition from the production of smaller batches of therapies for use in clinical trials, to the larger batches required by full-scale commercialization. The manufacturing process for cell and gene therapies is more complex than for other biologics, so CIRM is committed to creating a network to overcome those challenges.

In working towards that goal, CIRM is pleased to announce a new funding opportunity within our Infrastructure Program, the INFR5 Cell and Gene Therapy Manufacturing Network (Phase 1) Awards.  
 
The California Cell and Gene Therapy Manufacturing Network aims to establish a statewide manufacturing network comprising academic process development and GMP manufacturing facilities as well as industry manufacturing partners that will: 

  1. Accelerate and de-risk pathways to commercialization for cell and gene therapies 
  1. Advance industry standards and incorporate quality-by-design in cell and gene therapy manufacturing, and 
  1. Build a diverse, highly skilled manufacturing workforce in California. 

CIRM will issue two phases of awards governed by two separate requests for applications (RFAs). This RFA describes the first phase of awards that will fund California academic cell and gene therapy GMP manufacturing facilities to make initial progress toward the three network goals (described above) at their individual facilities. 

To apply for this award, please visit our website to download the Program Announcement and access a link to the application.  

Update: If you’re interested in learning more about the INFR5 Phase 1 Awards, eligibility requirements, the application and review process, and more, the CIRM team hosted an informational webinar in November. Watch a video recording of the webinar here. The slide deck is available here.