Our 2021-22 Annual Report is now online. It’s filled with information about the work we have done over the last year (we are on a fiscal calendar year from July 1 – June 30), the people who have helped us do that work, and some of the people who have benefited from that work. One of those is Dr. Alysson Muotri, a professor in the Departments of Pediatrics and Cellular & Molecular Medicine at the University of California, San Diego.
For Dr. Alysson Muotri, trying to unlock the secrets of the brain isn’t just a matter of scientific curiosity, it’s personal. He has a son with autism and Dr. Muotri is looking for ways to help him, and millions of others like him around the world.
He created the Tooth Fairy project where parents donated more than 3,000 baby teeth from children with autism and children who are developing normally. Dr. Muotri then turned cells from those teeth into neurons, the kind of brain cell affected by autism. He is using those cells to try and identify how the brain of a child with autism differs from a child who is developing normally.
“We’ve been using cells from this population to see what are the alterations (in the gene) and if we can revert them back to a normal state. If you know the gene that is affected, and autism has a strong genetic component, by genome sequencing you can actually find what are the genes that are affected and in some cases there are good candidates for gene therapy. So, you just put the gene back. And we can see that in the lab where we are correcting the gene that is mutated, the networks start to function in a way that is more neurotypical or normal. We see that as highly promising, there’s a huge potential here to help those individuals.”
He is also creating brain organoids, three-dimensional structures created from stem cells that mimic some of the actions and activities of the brain. Because these are made from human cells, not mice or other animals, they may be better at indicating if new therapies have any potential risks for people.
“We can test drugs in the brain organoids of the person and see if it works, see if there’s any toxicity before you actually give the drug to a person, and it will save us time and money and will increase our knowledge about the human brain.”
He says he still gets excited seeing how these cells work. “It’s amazing, it’s a miracle. Every time I see it, it’s like seeing dolphins in the sea because it’s so beautiful.”
Dr. Muotri is also a big proponent of diversity, equity and inclusion in scientific research. He says in the past it was very much a top-down model with scientists deciding what was important. He says we need to change that and give patients and communities a bigger role in shaping the direction of research.
“I think this is something we scientists have to learn, how to incorporate patients in our research. These communities are the ones we are studying, and we need to know what they want and not assume that what we want is what they want. They should be consulted on our grants, and they should participate in the design of our experiments. That is the future.”
The use of antiretroviral drugs has turned HIV/AIDS from a fatal disease to one that can, in many cases in the US, be controlled. But these drugs are not a cure. That’s why the governing Board of the California Institute for Regenerative Medicine (CIRM) voted to approve investing $6.85 million in a therapy that aims to cure the disease.
This is the 82nd clinical trial funded by CIRM.
There are approximately 38 million people worldwide living with HIV/AIDS. And each year there are an estimated 1.5 million new cases. The vast majority of those living with HIV do not have access to the life-saving antiretroviral medications that can keep the virus under control. People who do have access to the medications face long-term complications from them including heart disease, bone, liver and kidney problems, and changes in metabolism.
The antiretroviral medications are effective at reducing the viral load in people with HIV, but they don’t eliminate it. That’s because the virus that causes AIDS can integrate its DNA into long-living cells in the body and remain dormant. When people stop taking their medications the virus is able to rekindle and spread throughout the body.
Dr. William Kennedy and the team at Excision Bio Therapeutics have developed a therapeutic candidate called EBT-101. 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 is to eliminate or sufficiently reduce the hidden reservoirs of virus in the body to the point where the individual is effectively cured.
“To date only a handful of people have been cured of HIV/AIDS, so this proposal of using gene editing to eliminate the virus could be transformative,” says Dr. Maria Millan, President and CEO of CIRM. “In California alone there are almost 140,000 people living with HIV. HIV infection continues to disproportionately impact marginalized populations, many of whom are unable to access the medications that keep the virus under control. A functional cure for HIV would have an enormous impact on these communities, and others around the world.”
In a news release announcing they had dosed the first patient, Daniel Dornbusch, CEO of Excision, called it a landmark moment. “It is the first time a CRISPR-based therapy targeting an infectious disease has been administered to a patient and is expected to enable the first ever clinical assessment of a multiplexed, in vivo gene editing approach. We were able to reach this watershed moment thanks to years of innovative work by leading scientists and physicians, to whom we are immensely grateful. With this achievement, Excision has taken a major step forward in developing a one-time treatment that could transform the HIV pandemic by freeing affected people from life-long disease management and the stigma of disease.”
The Excision Bio Therapeutics team also scored high on their plan for Diversity, Equity and Inclusion. Reviewers praised them for adding on a partnering organization to provide commitments to serve underserved populations, and to engaging a community advisory board to help guide their patient recruitment.
One of the great pleasures of my job is getting to meet the high school students who take part in our SPARK or Summer Internship to Accelerate Regenerative Medicine Knowledge program. It’s a summer internship for high school students where they get to spend a couple of months working in a world class stem cell and gene therapy research facility. The students, many of whom go into the program knowing very little about stem cells, blossom and produce work that is quite extraordinary.
One such student is Tan Ieng Huang, who came to the US from China for high school. During her internship at U.C. San Francisco she got to work in the lab of Dr. Arnold Kriegstein. He is the Founding Director of the Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research at the University of California, San Francisco. Not only did she work in his lab, she took the time to do an interview with him about his work and his thoughts on the field.
It’s a fascinating interview and shows the creativity of our SPARK students. You will be seeing many other examples of that creativity in the coming weeks. But for now, enjoy the interview with someone who is a huge presence in the field today, by someone who may well be a huge presence in the not too distant future.
‘a tête-à-tête with Prof. Arnold Kriegstein’
Prof. Arnold Kriegstein is the Founding Director of the Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research at the University of California, San Francisco. Prof. Kriegstein is also the Co-Founder and Scientific Advisor of Neurona Therapeutics which seeks to provide effective and safe cell therapies for chronic brain disorder. A Clinician by training, Prof. Kriegstein has been fascinated by the intricate workings of the human brain. His laboratory focuses on understanding the transcriptional and signaling networks active during brain development, the diversity of neuronal cell types, and their fate potential. For a long time, he has been interested in harnessing this potential for translational and therapeutic intervention.
During my SEP internship I had the opportunity to work in the Kriegstein lab. I was in complete awe. I am fascinated by the brain. During the course of two months, I interacted with Prof. Kriegstein regularly, in lab meetings and found his ideas deeply insightful. Here’s presenting some excerpts from some of our discussions, so that it reaches many more people seeking inspiration!
Tan Ieng Huang (TH): Can you share a little bit about your career journey as a scientist?
Prof. Arnold Kriegstein (AK): I wanted to be a doctor when I was very young, but in high school I started having some hands-on research experience. I just loved working in the lab. From then on, I was thinking of combining those interests and an MD/PhD turned out to be an ideal course for me. That was how I started, and then I became interested in the nervous system. Also, when I was in high school, I spent some time one summer at Rockefeller University working on a project that involved operant conditioning in rodents and I was fascinated by behavior and the role of the brain in learning and memory. That happened early on, and turned into an interest in cortical development and with time, that became my career.
TH: What was your inspiration growing up, what made you take up medicine as a career?
AK: That is a little hard to say, I have an identical twin brother. He and I used to always share activities, do things together. And early on we actually became eagle scouts, sort of a boy scout activity in a way. In order to become an eagle scout without having to go through prior steps, we applied to a special program that the scouts had, which allowed us to shadow physicians in a local hospital. I remember doing that at a very young age. It was a bit ironic, because one of the evenings, they showed us films of eye surgery, and my brother actually fainted when they made an incision in the eye. The reason it makes me laugh now is because my brother became an eye surgeon many years later. But I remember our early experience, we both became very fascinated by medicine and medical research.
TH: What inspired you to start the Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research Institute?
AK: My interest in brain development over the years became focused on earlier stages of development and eventually Neurogenesis, you know, how neurons are actually generated during early stages of in utero brain development. In the course of doing that we discovered that the radial glial cells, which have been thought for decades to simply guide neurons as they migrate, turned out to actually be the neural stem cells, they were making the neurons and also guiding them toward the cortex. So, they were really these master cells that had huge importance and are now referred to as neural stem cells. But at that time, it was really before the stem cell field took off. But because we studied neurogenesis, because I made some contributions to understanding how the brain develops from those precursors or progenitor cells, when the field of stem cells developed, it was very simple for me to identify as someone who studied neural stem cells. I became a neural stem cell scientist. I started a neural stem cell program at Columbia University when I was a Professor there and raised 15 million dollars to seed the program and hired new scientists. It was shortly after that I was approached to join UCSF as the founder of a new stem cell program. And it was much broader than the nervous system; it was a program that covered all the different tissues and organ systems.
TH: Can you tell us a little bit about how stem cell research is contributing to the treatment of diseases? How far along are we in terms of treatments?
AK: It’s taken decades, but things are really starting to reach the clinic now. The original work was basic discovery done in research laboratories, now things are moving towards the clinic. It’s a really very exciting time. Initially the promise of stem cell science was called Regenerative medicine, the idea of replacing injured or worn-out tissues or structures with new cells and new tissues, new organs, the form of regeneration was made possible by understanding that there are stem cells that can be tweaked to actually help make new cells and tissues. Very exciting process, but in fact the main progress so far hasn’t been replacing worn out tissues and injured cells, but rather understanding diseases using human based model of disease. That’s largely because of the advent of induced pluripotent stem cells, a way of using stem cells to make neurons or heart cells or liver cells in the laboratory, and study them both in normal conditions during development and in disease states. Those platforms which are relatively easy to make now and are pretty common all over the world allow us to study human cells rather than animal cells, and the hope is that by doing that we will be able to produce conventional drugs and treatments that work much better than ones we had in the past, because they will be tested in actual human cells rather than animal cells.
TH: That is a great progress and we have started using human models because even though there are similarities with animal models, there are still many species-specific differences, right?
AK: Absolutely, in fact, one of the big problems now in Big Pharma, you know the drug companies, is that they invest millions and sometimes hundreds of millions of dollars in research programs that are based on successes in treating mice, but patients don’t respond the same way. So the hope is that by starting with a treatment that works on human cells it might be more likely that the treatment will work on human patients.
TH: What are your thoughts on the current challenges and future of stem cell research?
AK: I think this is an absolute revolution in modern medicine, the advent of two things that are happening right now, first the use of induced pluripotent stem cells, the ability to make pluripotent cells from adult tissue or cells from an individual allows us to use models of diseases that I mentioned earlier from actual patients. That’s one major advance. And the other is gene editing, and the combination of gene editing and cell-based discovery science allows us to think of engineering cells in ways that can make them much more effective as a form of cell therapy and those cell therapies have enormous promise. Right now, they are being used to treat cancer, but in the future, they might be able to treat heart attack, dementia, neurodegenerative diseases, ALS, Parkinson’s disease, a huge list of disorders that are untreatable right now or incurable. They might be approached by the combination of cell-based models, cell therapies, and gene editing.
TH: I know there are still some challenges right now, like gene editing has some ethical issues because people don’t know if there can be side effects after the gene editing, what are your thoughts?
AK: You know, like many other technologies there are uncertainties, and there are some issues. Some of the problems are off-target effects, that is you try to make a change in one particular gene, and while doing that you might change other genes in unexpected ways and cause complications. But we are understanding that more and more now and can make much more precise gene editing changes in just individual genes without affecting unanticipated areas of the genome. And then there are also the problems of how to gene-edit cells in a safe way. There are certain viral factors that can be used to introduce the gene editing apparatus into a cell, and sometimes if you are doing that in a patient, you can also have unwanted side effects from the vectors that you are using, often they are modified viral vectors. So, things get complicated very quickly when you start trying to treat patients, but I think these are all tractable problems and I think in time they will all be solved. It will be a terrific, very promising future when it comes to treating patients who are currently untreatable.
TH: Do you have any advice for students who want to get into this field?
AK: Yes, I think it’s actually never been a better time and I am amazed by the technologies that are available now. Gene editing that I mentioned before but also single cell approaches, the use of single cell multiomics revealing gene expression in individual cells, the molecular understanding of how individual cells are formed, how they are shaped, how they change from one stage to another, how they can be forced into different fates. It allows you to envision true Regenerative medicine, improving health by healing or replacing injured or diseased tissues. I think this is becoming possible now, so it’s a very exciting time. Anyone who has an interest in stem cell biology or new ways of treating diseases, should think about getting into a laboratory or a clinical setting. I think this time is more exciting than it’s ever been.
TH: So excited to hear that, because in school we have limited access to the current knowledge, the state-of-art. I want to know what motivates you every day to do Research and contribute to this field?
AK: Well, you know that I have been an MD/PhD, as I mentioned before, in a way, there are two different reward systems at play. In terms of the PhD and the science, it’s the discovery part that is so exciting. Going in every day and thinking that you might learn something that no one has ever known before and have a new insight into a mechanism of how something happens, why it happens. Those kinds of new insights are terrifically satisfying, very exciting. On the MD side, the ability to help patients and improve peoples’ lives is a terrific motivator. I always wanted to do that, was very driven to become a Neurologist and treat both adult and pediatric patients with neurological problems. In the last decade or so, I’ve not been treating patients so much, and have focused on the lab, but we have been moving some of our discoveries from the laboratory into the clinic. We have just started a clinical trial, of a new cell-based therapy for epilepsy in Neurona Therapeutics, which is really exciting. I am hoping it will help the patients but it’s also a chance to actually see something that started out as a project in the laboratory become translated into a therapy for patients, so that’s an achievement that has really combined my two interests, basic science, and clinical medicine. It’s a little late in life but not too late, so I’m very excited about that.
Tan Ieng Huang, Kriegstein Lab, SEP Intern, CIRM Spark Program2022
Glaucoma is the world’s leading cause of irreversible blindness. There is no cure and current treatments are only able to slow down the progression of the disease. Now research using stem cells to create a genetic blueprint of glaucoma is giving scientist a powerful new tool to combat the disease.
Glaucoma occurs when healthy retinal ganglion cells, which relay information from the eyes to the brain, are damaged and die. However, researchers were unable to really understand what was happening because the only way to look at retinal ganglion cells was through very invasive procedures.
So, researchers in Australia took skin cells from people with glaucoma and people with healthy eyes and, using the iPSC method, turned them into retinal ganglion cells. They were then able to map the genetic expression of these cells and compare the healthy cells with the diseased ones.
In an interview with Science Daily, Professor Joseph Powell, who led the team, says they were able to identify more than 300 unique genetic features which could provide clues as to what is causing the vision loss.
“The sequencing identifies which genes are turned on in a cell, their level of activation and where they are turned on and off — like a road network with traffic lights. This research gives us a genetic roadmap of glaucoma and identifies 312 sites in the genome where these lights are blinking. Understanding which of these traffic lights should be turned off or on will be the next step in developing new therapies to prevent glaucoma.”
Powell says by identifying underlying causes for glaucoma researchers may be able to develop new, more effective therapies.
DNA provides the code of life for nearly all living organisms. So, it’s no wonder that scientists have been studying DNA and the human genome (complete set of DNA) for decades.
In April 1953, James Watson and Francis Crick, in collaboration with Rosalind Franklin, first described the structure of DNA as a double helix. In April 2003, exactly 50 years later, scientists completed the Human Genome Project- a massive research effort to sequence and map all the genes that comprise the human genome.
You can celebrate National DNA Day this year by following scientists Lilly Lee and Tom Quinn at Takara Bio as they demonstrate how to extract DNA from strawberries. Their lesson plan guides mentors to teach about DNA and genomic research, starting with having students extract DNA on their own.
Laurel Barchas, one of the people behind the video has also played an important role at the California Institute for Regenerative Medicine (CIRM). She has collaborated with us on many projects over the years, including helping us build CIRM’s own education portal with lessons for high school students that meet Next Generation Science Standards.
Watch the video below and Click Here for the full lesson plan!
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 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:
Principal Investigator and Institution
Preclinical development of an exhaustion-resistant CAR-T stem cell for cancer immunotherapy
Ansuman Satpathy – Stanford University
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
Injectable, autologous iPSC-based therapy for spinal cord injury
Sarah Heilshorn – Stanford University
New noncoding RNA chemical entity for heart failure with preserved ejection fraction.
Eduardo Marban – Cedars-Sinai Medical Center
Modulation of oral epithelium stem cells by RSpo1 for the prevention and treatment of oral mucositis
Jeffrey Linhardt – Intact Therapeutics Inc.
Transplantation of genetically corrected iPSC-microglia for the treatment of Sanfilippo Syndrome (MPSIIIA)
People say that with age comes wisdom, kindness and confidence. What they usually don’t say is that it also comes with aches and pains and problems we didn’t have when we were younger. For example, as we get older our bones get thinner and more likely to break and less likely to heal properly.
That’s a depressing opening paragraph isn’t it. But don’t worry, things get better from here because new research from Germany has found clues as to what causes our bones to become more brittle, and what we can do to try and stop that.
Researchers at the Max Planck Institute for Biology of Ageing and CECAD Cluster of Excellence for Ageing Research at the University of Cologne have identified changes in stem cells from our bone marrow that seem to play a key role in bones getting weaker as we age.
To explain this we’re going to have to go into the science a little, so bear with me. One of the issues the researchers focused on is the role of epigenetics, this is genetic information that doesn’t change the genes themselves but does change their activity. Think of it like a light switch. The switch doesn’t change the bulb, but it does control when it’s on and when it’s off. So this team looked at the epigenome of MSCs, the stem cells found in the bone marrow. These cells play a key role in the creation of cartilage, bone and fat cells.
In a news release, Dr. Andromachi Pouikli, one of the lead researchers in the study, says these MSCs don’t function as well as we get older.
“We wanted to know why these stem cells produce less material for the development and maintenance of bones as we age, causing more and more fat to accumulate in the bone marrow. To do this, we compared the epigenome of stem cells from young and old mice. We could see that the epigenome changes significantly with age. Genes that are important for bone production are particularly affected.”
So, they took some stem cells from the bone marrow of mice and tested them with a solution of sodium acetate. Now sodium acetate has a lot of uses, including being used in heating pads, hand warmers and as a food seasoning, but in this case the solution was able to make it easier for enzymes to get access to genes and boost their activity.
“This treatment impressively caused the epigenome to rejuvenate, improving stem cell activity and leading to higher production of bone cells,” Pouikli said.
So far so good. But does this work the same way in people? Maybe so. The team analyzed MSCs from people who had undergone hip surgery and found that they showed the same kind of age-related changes as the cells from mice.
Clearly there’s a lot more work to do before we can even think about using this finding as a solution to aging bones. But it’s an encouraging start.
Glioblastoma (GBM) is a common type of aggressive brain tumor that is found in adults. Survival of this type of brain cancer is poor with just 40% survival in the first-year post diagnosis and 17% in the second year, according to the American Association of Neurological Surgeons. This disease has taken the life of former U.S. Senator John McCain and Beau Biden, the late son of U.S. President Joe Biden.
In a CIRM supported lab that conducted the study, Dr. Yanhong Shi and her team at City of Hope, a research and treatment center for cancer, have discovered a potential therapy that they have tested that has been shown to suppress GBM tumor growth and extend the lifespan of tumor-bearing mice.
Dr. Shi and her team first started by looking at PUS7, a gene that is highly expressed in GBM tissue in comparison to normal brain tissue. Dr. Qi Cui, a scientist in Dr. Shi’s team and the first author of the study, analyzed various databases and found that high levels of PUS7 have also been associated with worse survival in GBM patients. The team then studied different glioblastoma stem cells (GSCs), which play a vital role in brain tumor growth, and found that shutting off the PUS7 gene prevented GSC growth and self-renewal.
The City of Hope team then transplanted two kinds of GSCs, some with the PUS7 gene and some with the PUS7 gene turned off, into immunodeficient mice. What they found was that the mice implanted with the PUS7-lacking GSCs had less tumor growth and survived longer compared to the mice with the control GSCs that had PUS7 gene.
The team then proceeded to look for an inhibitor of PUS7 from a database of thousands of different compounds and drugs approved by the Food and Drug Administration (FDA). After identifying a promising compound, the researchers tested the potential therapy in mice implanted with GSCs with the PUS7 gene. What they found was remarkable. The therapy inhibited the growth of brain tumors in the mice and their survival was significantly prolonged.
“This is one of the most important studies in my lab in recent years and the first paper to show a causal link between PUS7-mediated modification and cancer in general and GBM in particular” says Dr. Shi. “It will be a milestone study for RNA modification in cancer.”
Elena Flowers, PhD, RN, an associate professor of physiological nursing at the University of California, San Francisco (UCSF) is joining the Board of the California Institute for Regenerative Medicine (CIRM), the state’s Stem Cell Agency.
Dr. Flowers was appointed to the Board by State Controller Betty T. Yee who said: “Ms. Flowers’ experience and express commitment to equitable health outcomes for California’s diverse communities will bring a valued perspective to the work ahead.”
Dr. Flowers is a member of the UCSF Institute for Human Genetics and the International Society of Nurses in Genetics. As a researcher her work focuses on genomics involving precision medicine and risk factors for cardiovascular health and type 2 diabetes. She is also a teacher and has lectured internationally on issues such as topics from racial disparities in Type 2 Diabetes to the implications of genomic technologies for the nursing workforce.
CIRM Board Chair, Jonathan Thomas, PhD, JD, welcomed the appointment: “Dr. Flowers brings a wealth of experience and expertise to our Board and, as a nurse, she will bring a different perspective to the work we do and help us in trying to better address the needs of underserved communities.”
“I am honored to have the opportunity to serve the citizens of California in this capacity,” says Dr. Flowers. “CIRM has ambitious goals, seeking to improve upon common limitations of public research agencies by its commitment to delivering meaningful findings and ultimately treatments for patients as rapidly as possible. I’m particularly committed to improving inclusion and access to these treatments across the entire diverse California population.”
Dr. Flowers got her undergraduate degree at UC Davis and then served as a research assistant at Zuckerberg San Francisco General Hospital. She then went on to get her MS and Doctor of Philosophy degrees at the UCSF School of Nursing.
In her spare time she has no spare time because she is the mother of two young daughters.
At CIRM we are modest enough to know that we can’t do everything by ourselves. To succeed we need partners. And in UC Davis we have a terrific partner. The work they do in advancing stem cell research is exciting and really promising. But it’s not just the science that makes them so special. It’s also their compassion and commitment to caring for patients.
What follows is an excerpt from an article by Lisa Howard on the work they do at UC Davis. When you read it you’ll see why we are honored to be a part of this research.
Gene therapy research at UC Davis
UC Davis’ commitment to stem cell and gene therapy research dates back more than a decade.
In 2010, with major support from the California Institute for Regenerative Medicine (CIRM), UC Davis launched the UC Davis Institute for Regenerative Cures, which includes research facilities as well as a Good Manufacturing Practice (GMP) facility.
Led by Jan Nolta, a professor of cell biology and human anatomy and the director of the UC Davis Institute for Regenerative Cures, the new center leverages UC Davis’ network of expert researchers, facilities and equipment to establish a center of excellence aimed at developing lifelong cures for diseases.
Nolta began her career at the University of Southern California working with Donald B. Kohn on a cure for bubble baby disease, a condition in which babies are born without an immune system. The blood stem cell gene therapy has cured more than 50 babies to date.
Work at the UC Davis Gene Therapy Center targets disorders that potentially can be treated through gene replacement, editing or augmentation.
“The sectors that make up the core of our center stretch out across campus,” said Nolta. “We work with the MIND Institute a lot. We work with the bioengineering and genetics departments, and with the Cancer Center and the Center for Precision Medicine and Data Sciences.”
A recent UC Davis stem cell study shows a potential breakthrough for healing diabetic foot ulcers with a bioengineered scaffold made up of human mesenchymal stem cells (MSCs). Another recent study revealed that blocking an enzyme linked with inflammation enables stem cells to repair damaged heart tissue. A cell gene therapy study demonstrated restored enzyme activity in Tay-Sachs disease affected cells in humanized mouse models.
“Some promising and exciting research right now at the Gene Therapy Center comes from work with hematopoietic stem cells and with viral vector delivery,” said Nolta.
Hematopoietic stem cells give rise to other blood cells. A multi-institutional Phase I clinical trial using hematopoietic stem cells to treat HIV-lymphoma patients is currently underway at UC Davis.
“We are genetically engineering a patient’s own blood stem cells with genes that block HIV infection,” said Joseph Anderson, an associate professor in the UC Davis Department of Internal Medicine. The clinical trial is a collaboration with Mehrdad Abedi, the lead principal investigator.
“When the patients receive the modified stem cells, any new immune system cell, like T-cell or macrophage, that is derived from one of these stem cells, will contain the HIV-resistant genes and block further infection,” said Anderson.
He explained that an added benefit with the unique therapy is that it contains an additional gene that “tags” the stem cells. “We are able to purify the HIV-resistant cells prior to transplantation, thus enriching for a more protective cell population.
Kyle David Fink
Kyle David Fink, an assistant professor of neurology at UC Davis, is affiliated with the Stem Cell Program and Institute for Regenerative Cures. His lab is focused on leveraging institutional expertise to bring curative therapies to rare, genetically linked neurological disorders.
“We are developing novel therapeutics targeted to the underlying genetic condition for diseases such as CDKL5 deficiency disorder, Angelman, Jordan and Rett syndromes, and Juvenile Huntington’s disease,” said Fink.
The lab is developing therapies to target the underlying genetic condition using DNA-binding domains to modify gene expression in therapeutically relevant ways. They are also creating novel delivery platforms to allow these therapeutics to reach their intended target: the brain.
“The hope is that these highly innovative methods will speed up the progress of bringing therapies to these rare neurodegenerative disease communities,” said Fink.
Jasmine Carter, a graduate research assistant at the UC Davis Stem Cell Program, October 18, 2019. (AJ Cheline/UC Davis)
Developing potential lifetime cures
Among Nolta’s concerns is how expensive gene therapy treatments can be.
“Some of the therapies cost half a million dollars and that’s simply not available to everyone. If you are someone with no insurance or someone on Medicare, which reimburses about 65 percent, it’s harder for you to get these life-saving therapies,” said Nolta.
To help address that for cancer patients at UC Davis, Nolta has set up a team known as the “CAR T Team.”
Chimeric antigen receptor (CAR) T-cell therapy is a type of immunotherapy in which a patient’s own immune cells are reprogrammed to attack a specific protein found in cancer cells.
“We can develop our own homegrown CAR T-cells,” said Nolta. “We can use our own good manufacturing facility to genetically engineer treatments specifically for our UC Davis patients.”
Although safely developing stem cell treatments can be painfully slow for patients and their families hoping for cures, Nolta sees progress every day. She envisions a time when gene therapy treatments are no longer considered experimental and doctors will simply be able to prescribe them to their patients.
“And the beauty of the therapy is that it can work for the lifetime of a patient,” said Nolta.