The California Institute for Regenerative (CIRM) has a number of education programs geared towards training the next generation of stem cell and gene therapy researchers. Each student comes to the program with their own motivation, their own reasons for wanting to be a scientist. This is Emily Smith’s story.
Surrounded by the cold white walls of a hospital room, my family suddenly found themselves on the other side of medicine. Void of any answers or cures, this new reality was full of doubt. As we witnessed assurance dwindle into a look of angst, the doctor’s lips stiffened as he faltered to say the words that would change my grandmother’s life forever. The spinal cancer they had gone in to extract was a misdiagnosed nothing. Instead, the exploration of his scalpel left her paralyzed from the chest down.
Seemingly simple day-to-day moments of my life became the building blocks of my passion for science today. Early realizations of the hurdles laced throughout my grandmother’s life. Vivid memories of my mother’s weary smile as she read articles on the newest advancements in stem cell research. Collectively, what these fragments of time nurtured was hope. I grew to have a dream that something different awaited us in the future. With purpose, I dove into the world of research as an undergraduate.
Today, I am a CIRM Bridges to Stem Cell Research Intern at the Sanford Consortium for Regenerative Medicine. I received my acceptance into the program about a month after my grandmother’s passing. She never saw a cure, let alone an effective treatment.
My position allows me to understand why stem cell research takes time. The road from the bench to the clinic is a painstakingly deliberate one. And although we seek reason and order from the world of science, what we often find is how imperfect it all can be. At its root, I found that research is truly a human endeavor. That is why, as scientists, we must grapple with our lack of knowledge and failures with humility.
CIRM’s programs that train tomorrow’s scientists, such as Bridges, are important because they do more than simply transfer over skills from one generation to the next. Over the next year, I get the valuable experience of working with scientists who share a common dream. They understand the urgency of their research, value the quality of their findings, and put patient needs first. This mentorship ensures that a sense of responsibility is carried on throughout this field.
I applied to this program because stem cell research gave my family the gift of hope. Now, on the other side of the wait, I wish to serve patients and families like my own. I am incredibly grateful to be a part of the Bridges program and I will devote the full extent of my knowledge towards the advancement of this field.
While stem cell and gene therapy research has advanced dramatically in recent years, there are still many unknowns and many questions remaining about how best to use these approaches in developing therapies. That’s why the governing Board of the California Institute for Regenerative Medicine (CIRM) today approved investing almost $25 million in 19 projects in early stage or Discovery research.
The awards are from CIRM’s DISC2 Quest program, which supports the discovery of promising new stem cell-based and gene therapy technologies that could be translated to enable broad use and ultimately, improve patient care.
“Every therapy that helps save lives or change lives begins with a researcher asking a simple question, “What if?”, says Dr. Maria T. Millan, the President and CEO of CIRM. “Our Quest awards reflect the need to keep supporting early stage research, to gain a deeper understanding of stem cells work and how we can best tap into that potential to advance the field.”
Dr. Judy Shizuru at Stanford University was awarded $1.34 million to develop a safer, less-toxic form of bone marrow or hematopoietic stem cell transplant (HCT). HCT is the only proven cure for many forms of blood disorders that affect people of all ages, sexes, and races worldwide. However, current methods involve the use of chemotherapy or radiation to destroy the patient’s own unhealthy blood stem cells and make room for the new, healthy ones. This approach is toxic and complex and can only be performed by specialized teams in major medical centers, making access particularly difficult for poor and underserved communities.
Dr. Shizuru proposes developing an antibody that can direct the patient’s own immune cells to kill diseased blood stem cells. This would make stem cell transplant safer and more effective for the treatment of many life-threatening blood disorders, and more accessible for people in rural or remote parts of the country.
Lili Yang UCLA Broad Stem Cell Research Center: Photo courtesy Reed Hutchinson PhotoGraphics
Dr. Lili Yang at UCLA was awarded $1.4 million to develop an off-the-shelf cell therapy for ovarian cancer, which causes more deaths than any other cancer of the female reproductive system.
Dr. Yang is using immune system cells, called invariant natural killer T cells (iNKT) to attack cancer cells. However, these iNKT cells are only found in small numbers in the blood so current approaches involve taking those cells from the patient and, in the lab, modifying them to increase their numbers and strength before transplanting them back into the patient. This is both time consuming and expensive, and the patient’s own iNKT cells may have been damaged by the cancer, reducing the likelihood of success.
In this new study Dr. Yang will use healthy donor cord blood cells and, through genetic engineering, turn them into the specific form of iNKT cell therapy targeting ovarian cancer. This DISC2 award will support the development of these cells and do the necessary testing and studies to advance it to the translational stage.
Timothy Hoey and Tenaya Therapeutics Inc. have been awarded $1.2 million to test a gene therapy approach to replace heart cells damaged by a heart attack.
Heart disease is the leading cause of death in the U.S. with the highest incidence among African Americans. It’s caused by damage or death of functional heart muscle cells, usually due to heart attack. Because these heart muscle cells are unable to regenerate the damage is permanent. Dr. Hoey’s team is developing a gene therapy that can be injected into patients and turn their cardiac fibroblasts, cells that can contribute to scar tissue, into functioning heart muscle cells, replacing those damaged by the heart attack.
One of my favorite phrases is “standing room only”. I got a chance to use it last week when we held a panel discussion on whether regenerative medicine could turn back the clock on aging. The event was at the annual conference of the International Society for Stem Cell Research (ISSCR) and more than 150 people packed into a conference room to hear the debate (so far more than 800 also watched a live stream of the event.)
It’s not surprising the place was jammed. The speakers included:
Dr. Deepak Srivastava, the President of the Gladstone Institutes, an expert on heart disease and the former President of ISSCR.
Dr. Stanley “Tom” Carmichael, Chair of the Department of Neurology at UCLA and an expert on strokes and other forms of brain injury.
Adrienne Shapiro, the mother of a daughter with sickle cell disease, a tireless patient advocate and supporter of regenerative medicine research, and the co-founder of Axis Advocacy, a family support organization for people with sickle cell.
And the topic is a timely one. It is estimated that as many as 90 percent of the people who die every day, die from diseases of aging such as heart disease, stroke, and cancer. So, what can be done to change that, to not just slow down or stop these diseases, but to turn back the clock, to repair the damage already done and replace cells and tissues already destroyed.
The conversation was enlightening, hopeful and encouraging, but also cautionary.
You can watch the whole event on our Youtube channel.
It is estimated that as many as 90 percent of people in industrialized countries who die every day, die from diseases of aging such as heart disease, stroke, and cancer. Of those still alive the numbers aren’t much more reassuring. More than 80 percent of people over the age of 65 have a chronic medical condition, while 68 percent have two or more.
Current medications can help keep some of those conditions, such as high blood pressure, under control but regenerative medicine wants to do a lot more than that. We want to turn back the clock and restore function to damaged organs and tissues and limbs. That research is already underway and we are inviting you to a public event to hear all about that work and the promise it holds.
On June 16th from 3p – 4.30p PST we are holding a panel discussion exploring the impact of regenerative medicine on aging. We’ll hear from experts on heart disease and stroke; we will look at other ground breaking research into aging; and we’ll discuss the vital role patients and patient advocates play in helping advance this work.
The discussion is taking place in San Francisco at the annual conference of the International Society for Stem Cell Research. But you can watch it from the comfort of your own home. That’s because we are going to live stream the event.
Jan Nolta, PhD, in her lab at UC Davis; Photo courtesy UC Davis
Working at CIRM you get to meet many remarkable people and Dr. Jan Nolta certainly falls into that category. Jan is the Director of the Stem Cell Program at UC Davis School of Medicine. She also directs the Institute for Regenerative Cures and is scientific director of both the Good Manufacturing Practice clean room facility at UC Davis and the California Umbilical Cord Blood Collection Program.
As if that wasn’t enough Jan is part of the team helping guide UC Davis’ efforts to expand its commitment to diversity, equity and inclusion using a variety of methods including telemedicine, to reach out into rural and remote communities.
She is on the Board of several enterprises, is the editor of the journal Stem Cells and, in her copious spare time, has dozens of aquariums and is helping save endangered species.
So, it’s no wonder we wanted to chat to her about her work and find out what makes her tick. Oh, and what rock bands she really likes. You might be surprised!
It’s hard to think of something as being rare when it affects up to 30 million Americans and 300 million people worldwide. But the truth is there are more than 6,000 conditions – those affecting 200,000 people or fewer – that are considered rare.
Today, February 28th, is Rare Disease Day. It’s a day to remind ourselves of the millions of people, and their families, struggling with these diseases. These conditions are also called or orphan diseases because, in many cases, drug companies were not interested in adopting them to develop treatments.
At the California Institute for Regenerative Medicine (CIRM), we have no such reservations. In fact last Friday our governing Board voted to invest almost $12 million to support a clinical trial for IPEX syndrome. IPEX syndrome is a condition where the body can’t control or restrain an immune response, so the person’s immune cells attack their own healthy tissue. This leads to the development of Type 1 diabetes, severe eczema, damage to the small intestines and kidneys and failure to thrive. It’s diagnosed in infancy, most of those affected are boys, and it is often fatal.
Taylor Lookofsky (who has IPEX syndrome) and his father Brian
IPEX is one of two dozen rare diseases that CIRM is funding a clinical trial for. In fact, more than one third of all the projects we fund target a rare disease or condition. Those include:
Some might question the wisdom of investing hundreds of millions of dollars in conditions that affect a relatively small number of patients. But if you see the faces of these patients and get to know their families, as we do, you know that often agencies like CIRM are their only hope.
Dr. Maria Millan, CIRM’s President and CEO, says the benefits of one successful approach can often extend far beyond one rare disease.
“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. 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.”
CIRM is proud to fund and spread awareness of rare diseases and invites you to watch this video about how they affect families around the world.
No one likes to be taken for granted, to feel that people only like you because you have scads of cash and they want some of it. That’s why it’s so lovely when you feel you are appreciated because of all the things money makes possible.
That’s how it felt when we saw City of Hope’s news release about our funding to train the next generation of scientists and leaders in the field of regenerative medicine. CIRM has awarded COH $4.86 million as part of its Research Training Program in Stem Cell Biology and Regenerative Medicine.
The program provides stem cell and gene therapy research training for up to 6 graduate students and 12 postdocs at the Beckman Research Institute of City of Hope. In addition to 3 years of research, the training includes coursework, patient engagement and community outreach activities.
“This program originates from City of Hope’s longstanding expertise in conducting clinical trials and applying fundamental stem cell biology and gene therapy to the treatment of diseases. The program reflects City of Hope’s commitment to ensuring that future scientific leaders understand the varied needs of diverse patient populations, and the inequities that presently affect both biomedical research and the development of and access to innovative therapies.”
Students in the program will have access to world class research facilities and will also benefit from the fact that their classrooms and laboratories are within walking distance from where patients are treated. We believe the best scientists need to have experience in working both at the laboratory bench and at the bedside, not only developing new therapies, but being able to deliver those therapies in a caring, compassionate way.
CIRM Bridges student discusses her poster presentation
At CIRM, the bread and butter of what we do is funding research and hopefully advancing therapies to patients. But the jam, that’s our education programs. Helping train the next generation of stem cell and gene therapy scientists is really inspiring. Watching these young students – and some are just high school juniors – come in and grasp the science and quickly become fluent in talking about it and creating their own experiments shows the future is in good hands.
Right now we fund several programs, such as our SPARK and Bridges internships, but they can’t cover everything, so last week the CIRM Board approved a new training program called COMPASS (Creating Opportunities through Mentorship and Partnership Across Stem Cell Science). The program will fill a critical need for skilled research practitioners who understand and contribute at all levels in the translation of science to medicine, from bench to bedside.
The objective of the COMPASS Training Program is to prepare a diverse group of undergraduate students for careers in regenerative medicine through the creation of novel recruitment and support mechanisms that identify and foster untapped talent within populations that are historically under-represented in the biomedical sciences. It will combine hands-on research with mentorship experiences to enhance transition of students to successful careers. A parallel objective is to foster greater awareness and appreciation of diversity, equity and inclusion in trainees, mentors, and other program participants
The CIRM Board approved investing $58.22 million for up to 20 applications for a five-year duration.
“This new program highlights our growing commitment to creating a diverse workforce, one that taps into communities that have been historically under-represented in the biomedical sciences,” says Dr. Maria T. Millan, President and CEO of CIRM. “The COVID19 pandemic made it clear that the benefits of scientific discovery are not always accessible to communities that most need them. CIRM is committed to tackling these challenges by creating a diverse and dedicated workforce that can meet the technical demands of taking novel treatment ideas and making them a reality.”
The Board also approved a new $80 million concept plan to expand the CIRM Alpha Stem Cell Clinic Network. The Network clinics are all in top California medical centers that have the experience and the expertise to deliver high-quality FDA-authorized stem cell clinical trials to patients.
There are currently five Alpha Clinics – UC San Diego; UCLA/UC Irvine; City of Hope; UCSF; UC Davis – and since 2015 they have hosted more than 105 clinical trials, enrolled more than 750 patients in these trials, and generated more than $95 million in industry contracts.
Each award will provide up to $8 million in funding over a five-year period. The clinics will have to include:
A demonstrated ability to offer stem cell and gene therapies to patients as part of a clinical trial.
Programs to help support the career development of doctors, nurses, researchers or other medical professionals essential for regenerative medicine clinical trials.
A commitment to data sharing and meeting CIRM’s requirements addressing issues of diversity, equity and inclusion and meeting the needs of California’s diverse patient population.
Every year millions of Americans suffer damage to their cartilage, either in their knee or other joints, that can eventually lead to osteoarthritis, pain and immobility. Today the governing Board of the California Institute for Regenerative Medicine (CIRM) approved two projects targeting repair of damaged cartilage.
The projects were among 17 approved by CIRM as part of the DISC2 Quest Discovery Program. The program promotes the discovery of promising new stem cell-based and gene therapy technologies that could be translated to enable broad use and ultimately, improve patient care.
Dr. Darryl D’Lima and his team at Scripps Health were awarded $1,620,645 to find a way to repair a torn meniscus. Every year around 750,000 Americans experience a tear in their meniscus, the cartilage cushion that prevents the bones in the knee grinding against each other. These injuries accelerate the early development of osteoarthritis, for which there is no effective treatment other than total joint replacement, which is a major operation. There are significant socioeconomic benefits to preventing disabling osteoarthritis. The reductions in healthcare costs are also likely to be significant.
The team will use stem cells to produce meniscal cells in the lab. Those are then seeded onto a scaffold made from collagen fibers to create tissue that resembles the knee meniscus. The goal is to show that, when placed in the knee joint, this can help regenerate and repair the damaged tissue.
This research is based on an earlier project that CIRM funded. It highlights our commitment to helping good science progress, hopefully from the bench to the bedside where it can help patients.
Dr. Kevin Stone: Photo courtesy Stone Research Foundation
Dr. Kevin Stone and his team at The Stone Research Foundation for Sports Medicine and Arthritis were awarded $1,316,215 to develop an approach to treat and repair damaged cartilage using a patient’s own stem cells.
They are using a paste combining the patient’s own articular tissue as well as Mesenchymal Stem Cells (MSC) from their bone marrow. This mixture is combined with an adhesive hydrogel to form a graft that is designed to support cartilage growth and can also stick to surfaces without the need for glue. This paste will be used to augment the use of a microfracture technique, where micro-drilling of the bone underneath the cartilage tear brings MSCs and other cells to the fracture site. The hope is this two-pronged approach will produce an effective and functional stem cell-based cartilage repair procedure.
If effective this could produce a minimally invasive, low cost, one-step solution to help people with cartilage injuries and arthritis.
The full list of DISC2 grantees is:
Application
Title
Principal Investigator and Institution
Amount
DISC2-13212
Preclinical development of an exhaustion-resistant CAR-T stem cell for cancer immunotherapy
Ansuman Satpathy – Stanford University
$ 1,420,200
DISC2-13051
Generating deeper and more durable BCMA CAR T cell responses in Multiple Myeloma through non-viral knockin/knockout multiplexed genome engineering
Julia Carnevale – UC San Francisco
$ 1,463,368
DISC2-13020
Injectable, autologous iPSC-based therapy for spinal cord injury
Sarah Heilshorn – Stanford University
$789,000
DISC2-13009
New noncoding RNA chemical entity for heart failure with preserved ejection fraction.
Eduardo Marban – Cedars-Sinai Medical Center
$1,397,412
DISC2-13232
Modulation of oral epithelium stem cells by RSpo1 for the prevention and treatment of oral mucositis
Jeffrey Linhardt – Intact Therapeutics Inc.
$942,050
DISC2-13077
Transplantation of genetically corrected iPSC-microglia for the treatment of Sanfilippo Syndrome (MPSIIIA)
There is no benefit in helping create a miraculous new therapy that can cure people and save lives if no one except the super-rich can afford it. That’s why the California Institute for Regenerative Medicine (CIRM) has made creating a roadmap to help make new treatments both available and affordable for all Californians a central pillar of its new 5-year Strategic Plan.
New treatments based on novel new technologies often seem to come with a gob-smacking price tag. When Kymriah, a CAR-T cell cancer therapy, was approved it cost $475,000 for one treatment course. When the FDA approved Zolgensma to treat spinal muscular atrophy, a genetic disorder that causes muscle wasting and weakness, the cost was $2.1 million for one dose.
Part of the pricing is due to high manufacturing cost and the specialized resources needed to deliver the treatments. The treatments themselves are showing that they can be one-and-done options for patients, meaning just one treatment may be all they need to be cured. But even with all that innovation and promise the high price may impact access to patients in need.
At CIRM we believe that if California taxpayer money has helped researchers develop a new therapy, Californians should be able to get that therapy. To try and ensure they can we have created the Accessibility and Affordability Working Group (AAWG). The groups mission is to find a way to overcome the hurdles that stand between a patient and the treatment they need.
The AAWG will work with politicians and policy makers, researchers and regulators, insurance companies and patient advocate organizations to gather the data and information needed to make these therapies available and affordable. Dr. Le Ondra Clark Harvey, a CIRM Board member and mental health advocate, says the barriers we have to confront are not just financial, they are racial and ethnic too.
We have already created a unique model for delivering stem cell therapies to patients through our Alpha Stem Cell Clinic Network. We are now setting out to build on that with our commitment to creating Community Care Centers of Excellence. But having world-class clinics capable of delivering life-saving therapies is not enough. We also need to make sure that Californians who need these treatments can get them regardless of who they are or their ability to pay.
The Stem Cellar 