You may have noticed last week that the official CIRM website and our beloved Stem Cellar blog were offline for a few days.
While we received some fun theories about the outage from our readers (we were not “hacked”, and it was not a ransomware attack), the explanation is much more technical: CIRM’s websites experienced an outage due to an issue with our Domain Name System (DNS).
We’re happy to report that our wonderful IT team has since taken care of the issue and our websites are back online. The CIRM team recognizes that website outages are never fun and apologizes for any inconvenience this may have caused.
Imagine you or someone you love is diagnosed with a rare disease and then told, “There is no cure, there are no treatments and because it’s so rare no one is even doing any research into developing a treatment.” Sadly for millions of people that’s an all-too-common occurrence.
There are around 7,000 rare diseases affecting some 25-30 million Americans. Some of these are ultra-rare conditions where worldwide there may be only a few hundred people, or even a few dozen, diagnosed with it. And of all these rare diseases, only 5% have an approved therapy.
For the people struggling with a rare disease, finding a sense of hope in the face of all this can be challenging. Some say it feels as if they have been abandoned by the health care system. Others fight back, working to raise both awareness about the disease and funds to help support research to develop a treatment. But doing that without experience in the world of fund raising and drug development can pose a whole new series of challenges.
That’s where Ultragenyx comes into the picture. The company has a simple commitment to patients. “We aim to develop safe and effective treatments for many serious rare diseases as fast as we can, and we are committed to helping the whole rare disease community move forward by sharing our science and expertise to advance future development, whether by us or others.”
They live up to that commitment by hosting a Rare Entrepreneur Bootcamp. Every year they bring together a dozen or so patient or family organizations that are actively raising funds for a potential treatment approach and give them a 3-day crash course in what they’ll need to know to have a chance to succeed in rare disease drug development.
Dr. Emil Kakkis, the founder of Ultragenyx, calls these advocates “warriors” because of all the battles they are going to face. He told them, “Get used to hearing no, because you are going to hear that a lot. But keep fighting because that’s the only way you get to ‘yes’.”
The bootcamp brings in experts to coach and advise the advocates on everything from presentation skills when pitching a potential investor, to how to collaborate with academic researchers, how to design a clinical trial, what they need to understand about manufacturing or intellectual property rights.
In a blog about the event, Arjun Natesan, vice president of Translational Research at Ultragenyx, wrote, “We are in a position to share what we’ve learned from bringing multiple drugs to market – and making the process easier for these organizations aligns with our goal of treating as many rare disease patients as possible. Our aim is to empower these organizations with guidance and tools and help facilitate their development of life-changing rare disease treatments.”
For the advocates it’s not just a chance to gain an understanding of the obstacles ahead and how to overcome them, it’s also a chance to create a sense of community. Meeting others who are fighting the same fight helps them realize they are not alone, that they are part of a bigger, albeit often invisible, community, working tirelessly to save the lives of their children or loved ones.
CIRM also has a commitment to supporting the search for treatments for rare diseases. We are funding more than two dozen clinical trials, in addition to many earlier stage research projects, targeting rare conditions.
Almost every day, we hear new reports from the thousands of regenerative medicine clinical trials globally sponsored by hundreds of companies and academic researchers. The California Institute for Regenerative Medicine (CIRM) is a leader in this space supporting some of the most advanced cell and gene therapy clinic trials for a variety of unmet medical needs. With all this current activity, it’s easy to forget that there were only a handful of clinical trials going on just seven years ago.
A New System for Delivering Treatments
In 2015, CIRM’s leadership recognized that we were on the cusp of introducing an array of new regenerative medicine clinical trials. However, there was one big concern—the existing clinical delivery systems had limited experience and capacity for managing these new and comparatively complex clinical trials. Cell and gene therapy regenerative medicine treatments require new systems for manufacturing, processing, and delivering treatments to patients.
In anticipation of the need for clinical bandwidth to support clinical trials, CIRM funded a network of California medical centers to develop teams dedicated to supporting regenerative medicine clinical trials. This network was called the Alpha Clinics Network.
Since 2015, the Alpha Clinics Network has grown to include six academic medical centers in California. The Network has treated over a thousand patients in more than 100 clinical trials. CIRM frequently encounters companies and academic researchers that are specifically interested in bringing their research to California to be performed in the Alpha Clinics Network. These research sponsors cite expertise in manufacturing, process, delivery and regulatory compliance as the Networks value proposition. One sponsor summed it up by indicating there are “fewer protocol deviations (errors)” in the Alpha Clinics.
Expanding the Alpha Clinics Network
As we enter 2022 with CIRM’s new five year strategic plan, a major aim is to create a broad network of medical centers capable of supporting diverse patient participation in clinical trials.
As a first step in this effort, CIRM recently announced $80 million in funding to expand the Alpha Clinics Network. This funding is intended to expand both the scale and scope of the Network. This funding will allow the scale to grow from six medical center to up to ten. Scale is important because as the number of clinical trials grow, there needs to be increased coordination and sharing of the workload. Alpha Clinic sites already collaborate to conduct individual clinical trials, and an expanded network will enable a greater number of trials to occur simultaneously.
In addition, the Expansion Awards will enable the Network to expand the scope of its activities to address current needs of the field. These needs include new research platforms for conducting clinical trials. For example, sites are looking at integrating new types of genomic (DNA sequencing) tools to support improved diagnosis and treatment of patients.
Also, CIRM is committed to funding research to treat neurological diseases. We anticipate network sites will develop advanced systems for delivering treatments to patients and evaluating the effectiveness of these treatments. In addition, sites will be developing training programs to address the growing workforce needs of the field of regenerative medicine.
In 2015, CIRM invested in the Alpha Clinics Network which positioned California as a leader in supporting regenerative medicine clinical trials. In 2022, we will be expanding the Network with the aim of delivering transformative treatments to a diverse California and the world. The Network will fulfill this aim by expanding its reach in the state, developing advanced research planforms and technologies, and by training the next generations of researchers with the skills to deliver patient treatments.
Watch a recording of our recent Alpha Clinics concept plan webinar:
IPEX syndrome is a rare condition where the body can’t control or restrain an immune response, so the person’s immune cells attack their own healthy tissue. The syndrome mostly affects boys, is diagnosed in the first year of life and is often fatal. Today the governing Board of the California Institute for Regenerative Medicine (CIRM) invested almost $12 million in a therapy being tested in a clinical trial to help these patients.
Children born with IPEX syndrome have abnormalities in the FOXP3 gene. This gene controls the production of a type of immune cell called a T Regulatory or Treg cell. Without a normal FOXP3 +Treg cells other immune cells attack the body leading to the development of IPEX syndrome, Type 1 diabetes, severe eczema, damage to the small intestines and kidneys and failure to thrive.
Current treatments involve the use of steroids to suppress the immune system – which helps ease symptoms but doesn’t slow down the progression of the disease – or a bone marrow stem cell transplant. However, a transplant requires a healthy, closely matched donor to reduce the risk of a potentially fatal transplant complication called graft vs host disease, in which the donated immune cells attack the recipient’s tissues.
Dr. Rosa Bacchetta and her team at Stanford University have developed a therapy using the patient’s own natural CD4 T cells that, in the lab, have been genetically modified to express the FoxP3 gene and converted into Treg cells. Those cells are then re-infused into the patient with a goal of determining if this approach is both safe and beneficial. Because the cells come from the patients there will be fewer concerns about the need for immunosuppressive treatment to stop the body rejecting the cells. It will also help avoid the problems of finding a healthy donor and graft vs host disease.
Dr. Bacchetta has received approval from the Food and Drug Administration (FDA) to test this approach in a Phase 1 clinical trial for patients suffering with IPEX syndrome.
“Children with IPEX syndrome clearly represent a group of patients with an unmet medical need, and this therapy could make a huge difference in their lives,” says Dr. Maria T. Millan, the President and CEO of CIRM. “Success of this treatment in this rare disease presents far-reaching potential to develop treatments for a larger number of patients with a broad array of immune disorders resulting from dysfunctional regulatory T cells.”
In addition to a strong scientific recommendation to fund the project the review team also praised it for the applicants’ commitment to the principles of Diversity, Equity and Inclusion in their proposal. The project proposes a wide catchment area, with a strong focus on enrolling people who are low-income, uninsured or members of traditionally overlooked racial and ethnic minority communities.
Advance World Class Science, Deliver Real World Solutions, Provide Opportunity for All.
These comprise the themes of our bold 5-year Strategic Plan. Since its launch less than two months ago, we have hit the ground running. Under the second and third strategic themes, we have already received ICOC approval for 2 concepts: Alpha Clinics Network Expansion and COMPASS educational program. We are now working on the execution of our first theme.
As indicated in our Strategic Plan, we strongly believe advancing world class science relies on collaborative research that leverages collective scientific knowledge. To that end, we have organized the virtual CIRM CNS Consortium Workshop (click for the agenda and see registration details below) to help us gather feedback from a panel of experts about the best approach for promoting a culture of collaboration.
The vision for this workshop was informed by multiple layers of stakeholder discussions and input that started even prior to the passage of Proposition 14. A quick walk down memory lane reminds us of CIRM’s early and deliberate effort to identify areas of opportunity for promoting a paradigm shift with a “team science” approach, especially in the context of complex diseases such as those affecting the CNS:
In 2019, we organized Brainstorming Neurodegeneration, a workshop where broad stakeholder input was received about the benefits and bottlenecks of developing a consortium approach where genomics and big data, novel stem cell models, and patient data could be collectively leveraged to advance the field of neurodegenerative research in a collaborative manner.
In 2020, just before the passage of Prop 14 and based on input from the 2019 workshop, we already had our eyes on target: the future of collaborative research is in sharable data, and sharing petabytes or more of data requires a collaborative data infrastructure. To better understand the status and bottlenecks of knowledge platforms that could leverage data sharing, we brought together a panel of experts at our 2020 Grantee Meeting. We were encouraged to learn that our laser-focused approach for promoting knowledge sharing was right on target and the panelists suggested that CIRM has a great opportunity to promote a paradigm shift in this area.
In early 2021, immediately after the passage of Prop 14 and building upon our previous conversations, we formed a Strategic Scientific Advisory Panel comprising a distinguished group of national and international scientists in the stem cell field. Once again, we were advised to expand sharable resources (especially in the context of stem cell modeling), bring more attention to complex diseases such as neurodegenerative and neuropsychiatric disorders, and facilitate knowledge sharing.
In mid 2021, as we were forming our Strategic Plan based on the above input, we pressure-tested our paradigm-shifting vision in a Town Hall and further gathered feedback from California stakeholders about their needs. Again, all arrows pointed to shared resources and data as critical elements for accelerating research.
Finally, in late 2021, just before the launch of our Strategic Plan, we organized a Data Biosphere Advisory Committee to advise us on ways to facilitate collaborative knowledge sharing. Here, we explored various models for leveraging and/or generating a data infrastructure in which CIRM-funded data could be managed and shared. The main outcome of this meeting was a recommendation to organize a workshop to test the feasibility and approach for generation of a CIRM knowledge platform. The Committee concluded that CIRM is uniquely positioned to contribute a wealth of data to the broader scientific community. A knowledge platform would provide an avenue for data sharing and collaboration with other groups that are dedicated to accelerating progress in the development of therapies, especially for CNS disorders.
We were walking on solid ground! In December of 2021, paralleling the input we had received from experts and stakeholders, we launched our 5-year Strategic Plan with the goal of advancing world class science by promoting a culture of collaboration.
To deliver on this goal, CIRM’s approach is to build the infrastructure (and we don’t mean bricks and mortar) that organizes and democratizes data through:
A network of shared resources labs that facilitate validation and standardization to support California regenerative medicine researchers
A data infrastructure where CIRM-funded data can be shared and external datasets leveraged to maximize real-world impact
We have held a virtual CNS Consortium Workshop on February 24th and 25th where we explored the development of these two resources through the deployment of a consortium and starting in the CNS space as a use case. While the discussions at the workshop centered on the CNS, the shared resources labs will be implemented across cell types and organs. The Data Infrastructure is intended to be a global resource for data sharing and fostering a culture of open science for all CIRM grantees—and the world. The complete workshop agenda can be found here.
Watch video recordings of Day 1 and Day 2 of the CNS workshop.
A recent discovery by stem cell scientists at Cedars-Sinai may help make cancer treatment more efficient and shorten the time it takes for people to recover from radiation and chemotherapy.
Published in the journal Nature Communications, the study by Dr. John Chute and his team (and co-funded by CIRM) revealed a mechanism through which the blood vessels in the bone marrow respond to injury, such as from chemotherapy or radiation.
When people receive radiation or chemotherapy as part of their cancer treatment, their blood counts plummet. It typically takes several weeks for these counts to return to normal levels. During this period patients are at risk for developing infections that may lead to hospitalization, disruptions in chemotherapy schedules, and even death.
Chute and his colleagues found that when mice receive radiation treatment, the cells that line the inner walls of the blood vessels in the bone marrow produce a protein called semaphorin 3A. This protein tells another protein, called neuropilin 1, to kill damaged blood vessels in the bone marrow.
When the investigators blocked the ability of these blood vessel cells to produce neuropilin 1 or semaphorin 3A, or injected an antibody that blocks semaphorin 3A communication with neuropilin 1, the veins and arteries in the bone marrow regenerated faster following irradiation. In addition, blood counts increased dramatically after one week.
“We’ve discovered a mechanism that appears to control how blood vessels regenerate following injury,” said Chute, senior author of the paper. “Inhibiting this mechanism causes rapid recovery of the blood vessels and blood cells in bone marrow following chemotherapy or irradiation.”
In principle, Chute said, targeting this mechanism could allow patients to recover following chemotherapy in one to two weeks, instead of three or four weeks as currently experienced.
Christina M. Termini, a post-doctoral scientist at the David Geffen School of Medicine at UCLA, was the first author of this study. Read the source press release here.
Through our new Strategic Plan, the California Institute for Regenerative Medicine (CIRM) will build inclusive participation opportunities for all stakeholders, from the students to the workforce to the patients.
That said, it’s important to recognize the important work CIRM has already done to train the next generation of scientists and grow the field of regenerative medicine. Alessandra’s story illustrates just one of the many ways we have done that in the past, and we intend to do even more in the future.
Gaining Exposure to Innovative Research
CIRM Scholar Alessandra Rodriguez y Baena was a Master’s student at Cal Poly, San Luis Obispo. With the support of CIRM’s Bridges Program, she became a CIRM intern in the Willert Lab at UC San Diego.
As a student researcher, CIRM provided her with supportive mentors (both at Cal Poly and UCSD), hands-on training in the field of regenerative medicine, and exposure to innovative ideas and research. The program also provided Alessandra with a stipend to help cover expenses. This was particularly helpful for students from low-income backgrounds who otherwise might not be able to afford to go to college.
“I always recommend my undergraduate students who are interested in research to apply to the Bridges programs because, to me, it was a defining experience that led me to pursue my passion for stem cell research as well as teaching,” Alessandra says.
Alessandra is now a fourth-year PhD student in the Forsberg Lab in the department of Molecular, Cell & Developmental Biology at UC Santa Cruz where she is studying the epigenetic regulation of aging in bone marrow stem cells.
In addition to Alessandra, CIRM has provided opportunities in science to nearly 3,000 students across California. These include high schoolers in our SPARK Program, as well as undergrads and graduate students in our Bridges Program and pre and post-doctoral students in our Research Training program. Many of these are from diverse backgrounds.
A Game Changer
Sneha Santosh, another CIRM Scholar, first heard about CIRM’s Bridges to Stem Cell Therapy and Research internship when she was graduating from the UC Davis. She was pursuing a degree in microbial biotechnology and thinking about getting a master’s degree in biotechnology. She said the opportunity to be part of a program that is training the next generation of scientists was a game changer for her.
Through the Bridges Program, she learned about stem cells’ power to treat a disease’s root cause rather than just the symptoms. She saw how these transformative therapies changed people’s lives.
Today, she is a cell culture associate with Novo Nordisk, a leading global healthcare company in Fremont, California
CIRM’s New Strategic Plan
Alessandra and Sneha’s stories capture CIRM’s commitment to building education and training programs, and providing opportunities to build a diverse, highly skilled regenerative medicine workforce. We’ll be covering this ambitious yet achievable goal in our upcoming blog posts.
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.
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.
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.
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.
We shared our most exciting updates and newsworthy stories—topics ranging from stem cell research to diversity in science—right here on The Stem Cellar. Nearly 100,000 readers followed along throughout the year!
In case you missed them, here’s a recap of our most popular blogs of 2021. We look forward to covering even more topics in 2022 and send a sincere thank you to our wonderful Stem Cellar readers for tuning in!
Type 1 Diabetes Therapy Gets Go-Ahead for Clinical Trial This past year, ViaCyte and CRISPR Therapeutics put their heads together to develop a novel treatment for type 1 diabetes (T1D). The result was an implantable device containing embryonic stem cells that develop into pancreatic progenitor cells, which are precursors to the islet cells destroyed by T1D. The hope is that when this device is transplanted under a patient’s skin, the progenitor cells will develop into mature insulin-secreting cells that can properly regulate the glucose levels in a patient’s blood.
CIRM Builds Out World Class Team With 5 New hires After the Passage of Proposition 14 in 2020, CIRM set ambitious goals as part of our new strategic plan. To help meet these goals and new responsibilities, we added a new group of talented individuals with backgrounds in legal, finance, human resources, project management, and more. The CIRM team will continue to grow in 2022, as we add more team members who will work to fulfil our mission of accelerating world class science to deliver transformative regenerative medicine treatments in an equitable manner to a diverse California and world.
Meet Xenobots 2.0 – the Next Generation of Living Robots In 2020, we wrote about how researchers at the University of Vermont and Tufts University were able to create what they call xenobots – the world’s first living, self-healing robots created from frog stem cells. Fast forward to 2021: the same team created an upgraded version of these robots that they have dubbed Xenobots 2.0. These upgraded robots can self-assemble a body from single cells, do not require muscle cells to move, and demonstrate the capability to record memory. Interesting stuff!
CIRM Board Approves New Clinical Trial for ALS In June, CIRM’s governing Board awarded $11.99 million to Cedars-Sinai to fund a clinical trial for amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease. Clive Svendsen, Ph.D. and his team will be conducting a trial that uses a combined cell and gene therapy approach as a treatment for ALS. The trial builds upon CIRM’s first ALS trial, also conducted by Cedars-Sinai and Svendsen.
COVID is a Real Pain in the Ear Viral infections are a known cause of hearing loss and other kinds of infection. That’s why before the pandemic started, Dr. Konstantina Stantovic at Massachusetts Eye and Ear and Dr. Lee Gherke at MIT had been studying how and why things like measles, mumps and hepatitis affected people’s hearing. After COVID hit, they heard reports of patients experiencing sudden hearing loss and other problems, so they decided to take a closer look.
And there you have it: The Stem Cellar’s top blog posts of 2021! If you’re looking for more ways to get the latest updates from The Stem Cellar and CIRM, follow us on social media on Facebook, Twitter, LinkedIn, and Instagram.