CIRM-funded stem cell clinical trial patients: Where are they now?

Ronnie with his parents Pawash Priyank and Upasana Thakur.

Since its launch in 2004, the California Institute for Regenerative Medicine (CIRM) has been a leader in growing the stem cell and regenerative medicine field while keeping the needs of patients at the core of its mission. 

To date, CIRM has:  

  • Advanced stem cell research and therapy development for more than 75 diseases. 
  • Funded 76 clinical trials with 3,200+ patients enrolled. 
  • Helped cure over 40 children of fatal immunological disorders with gene-modified cell therapies. 

One of these patients is Ronnie, who just days after being born was diagnosed with severe combined immunodeficiency (SCID), a rare immune disorder that is often fatal within two years. 

A recent photo of Ronnie enjoying a day at the beach.

Fortunately, doctors told his parents about a CIRM-funded clinical trial conducted by UC San Francisco and St. Jude Children’s Hospital. Doctors took some of Ronnie’s own blood stem cells and, in the lab, corrected the genetic mutation that caused the condition. They then gave him a mild dose of chemotherapy to clear space in his bone marrow for the corrected cells to be placed and to grow. Over the next few months, the blood stem cells created a new blood supply and repaired Ronnie’s immune system. He is now a happy, healthy four-year-old boy who loves going to school with other children. 

Evie Junior participated in a CIRM-funded clinical trial in 2020. Photo: Jaquell Chandler

Another patient, Evie Junior, is pioneering the search for a cure for sickle cell disease: a painful, life-threatening condition.  

In July of 2020, Evie took part in a CIRM-funded clinical trial where his own blood stem cells were genetically modified to overcome the disease-causing mutation. Those cells were returned to him, and the hope is they’ll create a sickle cell-free blood supply. Evie hasn’t had any crippling bouts of pain or had to go to the hospital since his treatment.

To demonstrate treatment efficacy, study investigators will continue to monitor the recovery of Evie, Ronnie, and others who participate in clinical trials. 

CIRM’s new strategic plan seeks to help real life patients like Ronnie and Evie by optimizing its clinical trial funding partnership model to advance more therapies to FDA for approval.  

In addition, CIRM will develop ways to overcome manufacturing hurdles for the delivery of regenerative medicine therapies and create Community Care Centers of Excellence that support diverse patient participation in the rapidly maturing regenerative medicine landscape. Stay tuned as we cover these goals here on The Stem Cellar. 

To learn more about CIRM’s approach to deliver real world solutions for patients, check out our new 5-year strategic plan.  

Empowering and connecting California’s research ecosystem through shared labs

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A shared stem cell laboratory at UCLA

The California Institute for Regenerative Medicine (CIRM) has set ambitious goals in its new 5-year strategic plan. Made possible by renewed funding through Proposition 14, the plan lays out a roadmap for CIRM as the agency continues to advance world class science, deliver real world solutions, and provide opportunity for all.

In regenerative medicine (and many other fields), the lack of protocol standardization and lack of analytical toolkits make it difficult to access novel and reliable technology platforms.

CIRM recognizes these limitations, and as a response, the Agency has made it a goal in the “Prop 14 era” to develop next-generation competency hubs that empower and connect California’s research ecosystem.

One example of such competency hubs is the shared labs. The concept of shared labs isn’t new to CIRM. In fact, CIRM has awarded a total of 17 shared research laboratory grants to academic and nonprofit research institutions to provide lab space for innovative stem cell research and training.

CIRM will expand this shared lab model by creating networks of specialized competency hubs that offer knowledge and/or materials in cell and gene therapy development. These hubs will encourage collaborations and provide intra- and inter-institutional access to various competencies by sharing facilities, training, equipment, materials, protocols, and/or expertise.

As an example, a disease modeling competency hub would provide access to innovative models used to study diseases, collaborative researchers, shared facilities for conducting research, equipment and training programs for deriving or differentiating cell lines, etc. These collaborative environments would encourage researchers to work together with a team science approach, which would significantly accelerate discovery and therapy development.

Some of these hubs will also serve as a workforce training program for local and neighboring institutions. Most California state universities and community colleges have neither the financial nor experiential bandwidth for innovative research. They may, however, harbor a potentially diverse future workforce who could learn these techniques and use the technology platforms for small scale research. Training may also trigger the interest of the future workforce in pursuing the field of regenerative medicine.  

The competency hubs will also constitute part of the CIRM collaborative ecosystem making all their data available through the CIRM data infrastructure hub, also known as CIRM knowledge networks.

Finally, the network of competency hubs will greatly benefit the people of California by expanding geographic access to diverse communities and providing researchers with a unique opportunity of exposure to state-of-the-art platforms.

Visit this page to learn more about CIRM’s new 5-year Strategic Plan, and stay tuned as we share progress updates on our 5-year goals here on the Stem Cellar.

A CIRM-funded therapy for a deadly blood cancer gets approval for Phase 3 clinical trial

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Michael Wang, MD (right) of the Department of Lymphoma & Myeloma at MD Anderson Cancer Center will lead the Phase 3 clinical

Oncternal Therapeutics, Inc. is celebrating an encouraging milestone at the start of the new year following a successful End-of-Phase 2 meeting with the FDA. 

Specifically, the FDA agreed on key elements of the company’s potentially pivotal Phase 3 clinical trial of zilovertamab, which offers potential treatment advantages to patients suffering from relapsed or refractory mantle cell lymphoma (MCL). Zilovertamab (previously called cirmtuzumab because it was developed with CIRM fundingis the company’s investigational anti-ROR1 monoclonal antibody. 

Mantle cell lymphoma is an aggressive form of blood cancer that develops when white blood cells, which are a key component of our immune system and help fight infections, grow out of control. 

The California Institute for Regenerative Medicine (CIRM) funded an earlier-stage trial conducted by Oncternal Therapeutics in collaboration with UC San Diego. 

The Phase 3 clinical trial will be led by Dr. Michael Wang, of the Department of Lymphoma & Myeloma at MD Anderson Cancer Center. The trial will randomize patients with relapsed or refractory MCL who have experienced stable disease or a partial response after receiving four months of oral ibrutinib therapy to receive either blinded zilovertamab or placebo. All patients will continue receiving oral ibrutinib.  

The study (ZILO-301) will be conducted internationally in at least 50 centers experienced in treating MCL, and is expected to begin in the second quarter of 2022.  

The researchers hope the treatment will lead to progression-free survival for patients getting zilovertamab and that this will lead to FDA approval of the therapy. 

The company is also planning to conduct study ZILO-302, an open-label companion study of zilovertamab plus ibrutinib for patients who have progressive disease during the initial four months of ibrutinib monotherapy from Study ZILO-301. 

Read the full release of the study here and be sure to follow the Stem Cellar blog for more updates on the clinical trial.  

The Most Read Stem Cellar Blog Posts of 2021

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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!  

Image courtesy of ViaCyte
  1. 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’s new General Counsel Kevin Marks
  1. 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. 
Image source: Doug Blackiston
  1. 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! 
Pictured: Clive Svendsen, Ph.D.
  1. 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. 
Image courtesy of Karolina Grabowska
  1. 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 FacebookTwitterLinkedIn, and Instagram

Researchers develop a stem cell-based implant for cartilage restoration and treating osteoarthritis

The Plurocart’s scaffold membrane seeded with stem cell-derived chondrocytes. Image courtesy of USC Photo/Denis Evseenko.

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Researchers at the Keck School of Medicine of USC have used a stem cell-based bio-implant to repair cartilage and delay joint degeneration in a large animal model. This paves the way to potentially treat humans with cartilage injuries and osteoarthritis, which occurs when the protective cartilage at the ends of the bones wears down over time. The disorder affects millions worldwide.

 The researchers are using this technology to manufacture the first 64 implants to be tested on humans with support from a $6 million grant from the California Institute for Regenerative Medicine (CIRM).

Researchers Dr. Denis Evseenko, and Dr. Frank Petrigliano led the development of the therapeutic bio-implant, called Plurocart. It’s composed of a scaffold membrane seeded with stem cell-derived chondrocytes, the cells responsible for producing and maintaining healthy articular cartilage tissue. 

In the study, the researchers implanted the Plurocart membrane into a pig model of osteoarthritis, resulting in the long-term repair of articular cartilage defects. Evseenko said the findings are significant because the implant fully integrated in the damaged articular cartilage tissue and survived for up to six months. “Previous studies have not been able to show survival of an implant for such a long time,” Evseenko added.

The researchers also found that the cartilage tissue generated was strong enough to withstand compression and elastic enough to accommodate movement without breaking.

Osteoarthritis, an often-painful disorder, can affect any joint, but most commonly affects those in our knees, hips, hands and spine. The USC researchers hope their implant will help prevent the development of arthritis and alleviate the need for invasive joint replacement surgeries.

“Many of the current options for cartilage injury are expensive, involve complex logistical planning, and often result in incomplete regeneration,” said Petrigliano. “Plurocart represents a practical, inexpensive, one-stage therapy that may be more effective in restoring damaged cartilage and improve the outcome of such procedures.”

Read the full study here and learn more about the CIRM grant here.

Newly-developed Organoid Mimics How Gut and Heart Tissues Arise Cooperatively From Stem Cells 

Microscopy image of the new type of organoid created by Todd McDevitt, Ana Silva, and their colleagues in which heart tissue (red, purple, and orange masses) and gut tissue (blue and green masses) are growing together. Captured by Ana Silva.
Microscopy image of the new type of organoid created by Todd McDevitt, Ana Silva, and their colleagues in which heart tissue (red, purple, and orange masses) and gut tissue (blue and green masses) are growing together. Captured by Ana Silva. Image courtesy of Gladstone Institutes.

Scientists at Gladstone Institutes have discovered how to grow a first-of-its-kind organoid—a three-dimensional, organ-like cluster of cells—that mimics how gut and heart tissues arise cooperatively from stem cells.  

The study was supported by a grant from CIRM and the Gladstone BioFulcrum Heart Failure Research Program. 

Gladstone Senior Investigator Todd McDevitt, PhD said this first-of-its-kind organoid could serve as a new tool for laboratory research and improve our understanding of how developing organs and tissues cooperate and instruct each other. 

McDevitt’s team creates heart organoids from human induced pluripotent stem cells, coaxing them into becoming heart cells by growing them in various cocktails of nutrients and other naturally occurring substances. In this case, the scientists tried a different cocktail to potentially allow a greater variety of heart cells to form. 

To their surprise, they found that the new cocktail led to organoids that contained not only heart, but also gut cells. 

“We were intrigued because organoids normally develop into a single type of tissue—for example, heart tissue only,” says Ana Silva, PhD, a postdoctoral scholar in the McDevitt Lab and first author of the new study. “Here, we had both heart and gut tissues growing together in a controlled manner, much as they would in a normal embryo.” 

Shown here is the study’s first author, Ana Silva, a postdoctoral scholar in the McDevitt Lab. Image courtesy of Gladstone Institutes.

The researchers also found that compared to conventional heart organoids, the new organoids resulted in much more complex and mature heart structures—including some resembling more mature-like blood vessels. 

These organoids offer a promising new look into the relationship between developing tissues, which has so far relied on growing single-tissue organoids separately and then attempting to combine them. Not only that, the organoids could help clarify how the process of human development can go wrong and provide insight on congenital disorders like chronic atrial and intestinal dysrhythmias that are known to affect both heart and gut development. 

“Once it became clear that the presence of the gut tissue contributed to the maturity of the heart tissue, we realized we had arrived at something new and special,” says McDevitt. 

Read the official release about this study on Gladstone’s website

The study findings are published in the journal Cell Stem Cell.

Now-Defunct For-Profit Stem Cell Clinic Ordered to Pay $5.1 Million for Scamming Patients Through False Advertising

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Photo of New York Attorney General Letitia James courtesy Wikimedia commons

A now-defunct New York City for-profit stem cell clinic — Park Avenue Stem Cell — was order by court to pay $5.1 million in potential consumer restitution, penalties, and costs for fraudulently and illegally advertising their stem cell procedures. The judgment resolves a 2019 lawsuit by New York State Attorney General Letitia James which claimed the defendants’ scammed patients out of thousands of dollars each for unproven and potentially harmful medical treatments involving stem cells. 

According to the lawsuit, the clinic falsely advertised on their website, social media, television, and foreign language newspapers that they could treat a variety of serious medical conditions — including erectile dysfunction and Parkinson’s disease — using patients’ own stem cells. Consumers paid the clinic nearly $4,000 per procedure, with some consumers paying more than $20,000 for multiple procedures. Most of the procedures involved adipose stem cells, which are derived from a patient’s own fat tissues.   

The court says the defendants misrepresented that their procedures were approved by the U.S. Food and Drug Administration (FDA), that their patients were participating in an established research study, and that their procedures had been endorsed by several scientific and medical organizations.   

As a state agency, CIRM’s duty is to educate the public about the concerns over “stem cell tourism” and the growing number of predatory clinics that advertise unproven stem cell therapies at great cost to the patient.  

In addition to hosting public forums on stem cell tourism concerns and resources for patients seeking stem cell treatments, CIRM partnered with California State Senator Ed Hernandez (D-West Covina) to create a new law that attempts to address the issue. The bill, SB 512, was passed in 2017 and now requires medical clinics whose stem cell treatments are not FDA approved to post notices and provide handouts to patients warning them about the potential risk.  

Read more about this lawsuit at the New York Attorney general’s website.