Coronavirus

Everything you wanted to know about COVID vaccines but never got a chance to ask

/ Kevin McCormack / 1 Comment

All this month we are using our blog and social media to highlight a new chapter in CIRM’s life, thanks to the voters approving Proposition 14. We are looking back at what we have done since we were created in 2004, and also looking forward to the future. Today we feature a rare treat, an interview with Moderna’s Dr. Derrick Rossi.

Moderna co-founder Dr. Derrick Rossi

It’s not often you get a chance to sit down with one of the key figures in the fight against the coronavirus and get to pick his brain about the best ways to beat it. We were fortunate enough to do that on Wednesday, talking to Dr. Derrick Rossi, the co-founder of Moderna, about the vaccine his company has developed.

CIRM’s President and CEO, Dr. Maria Millan, was able to chat to Dr. Rossi for one hour about his background (he got support from CIRM in his early post-doctoral research at Stanford) and how he and his colleagues were able to develop the COVID-19 vaccine, how the vaccine works, how effective it is, how it performs against new variations of the virus.

He also told us what he would have become if this science job hadn’t worked out.

All in all it was a fascinating conversation with someone whose work is offering a sense of hope for millions of people around the world.

If you missed it first time around you can watch it here.

How a CIRM scholar helped create a life-saving COVID vaccine

/ Kevin McCormack / 1 Comment

Dr. Derrick Rossi might be the most famous man whose name you don’t recognize. Dr. Rossi is the co-founder of Moderna. Yes, that Moderna. The COVID-19 vaccine Moderna. The vaccine that in clinical trials proved to be around 95 percent effective against the coronavirus.

Dr. Rossi also has another claim to fame. He is a former CIRM scholar. He did some of his early research, with our support, in the lab of Stanford’s Dr. Irv Weissman.

So how do you go from a lowly post doc doing research in what, at the time, was considered a rather obscure scientific field, to creating a company that has become the focus of the hopes of millions of people around the world?  Well, join us on Wednesday, January 27th at 9am (PST) to find out.

CIRM’s President and CEO, Dr. Maria Millan, will hold a live conversation with Dr. Rossi and we want you to be part of it. You can join us to listen in, and even post questions for Dr. Rossi to answer. Think of the name dropping credentials you’ll get when say to your friends; “Well, I asked Dr. Rossi about that and he told me…..”

Being part of the conversation is as simple as clicking on this link:

After registering, you will receive a confirmation email containing information about joining the webinar.

We look forward to seeing you there.

CIRM funded researchers discover link between Alzheimer’s gene and COVID-19

/ Yimy Villa / Leave a comment
Dr. Yanhong Shi (left) and Dr. Vaithilingaraja Arumugaswami (right)

All this month we are using our blog and social media to highlight a new chapter in CIRM’s life, thanks to the voters approving Proposition 14. We are looking back at what we have done since we were created in 2004, and also looking forward to the future. Today we focus on groundbreaking CIRM funded research related to COVID-19 that was recently published.

It’s been almost a year since the world started hearing about SARS-CoV-2, the virus that causes COVID-19.  In our minds, the pandemic has felt like an eternity, but scientists are still discovering new things about how the virus works and if genetics might play a role in the severity of the virus.  One population study found that people who have ApoE4, a gene type that has been found to increase the risk of developing Alzheimer’s, had higher rates of severe COVID-19 and hospitalizations.

It is this interesting observation that led to important findings of a study funded by two CIRM awards ($7.4M grant and $250K grant) and conducted by Dr. Yanhong Shi at City of Hope and co-led by Dr. Vaithilingaraja Arumugaswami, a member of the UCLA Broad Stem Cell Research Center.  The team found that the same gene that increases the risk for Alzheimer’s disease can increase the susceptibility and severity of COVID-19.

At the beginning of the study, the team was interested in the connection between SARS-CoV-2 and its effect on the brain.  Due to the fact that patients typically lose their sense of taste and smell, the team theorized that there was an underlying neurological effect of the virus.  

The team first created neurons and astrocytes.  Neurons are cells that function as the basic working unit of the brain and astrocytes provide support to them.  The neurons and astrocytes were generated from induced pluripotent stem cells (iPSCs), which are a kind of stem cell that can become virtually any type of cell and can be created by “reprogramming” the skin cells of patients.  The newly created neurons and astrocytes were then infected with SARS-CoV-2 and it was found that they were susceptible to infection.

Next, the team used iPSCs to create brain organoids, which are 3D models that mimic certain features of the human brain.  They were able to create two different organoid models: one that contained astrocytes and one without them.  They infected both brain organoid types with the virus and discovered that those with astrocytes boosted SARS-CoV-2 infection in the brain model. 

The team then decided to further study the effects of ApoE4 on susceptibility to SARS-CoV-2.  They did this by generating neurons from iPSCs “reprogrammed” from the cells of an Alzheimer’s patient.  Because the iPSCs were derived from an Alzheimer’s patient, they contained ApoE4.  Using gene editing, the team modified some of the ApoE4 iPSCs created so that they contained ApoE3, which is a gene type considered neutral.  The ApoE3 and ApoE4 iPSCs were then used to generate neurons and astrocytes.

The results were astounding.  The ApoE4 neurons and astrocytes both showed a higher susceptibility to SARS-CoV-2 infection in comparison to the ApoE3 neurons and astrocytes.  Moreover, while the virus caused damage to both ApoE3 and ApoE4 neurons, it appeared to have a slightly more severe effect on ApoE4 neurons and a much more severe effect on ApoE4 astrocytes compared to ApoE3 neurons and astrocytes. 

“Our study provides a causal link between the Alzheimer’s disease risk factor ApoE4 and COVID-19 and explains why some (e.g. ApoE4 carriers) but not all COVID-19 patients exhibit neurological manifestations” says Dr. Shi. “Understanding how risk factors for neurodegenerative diseases impact COVID-19 susceptibility and severity will help us to better cope with COVID-19 and its potential long-term effects in different patient populations.”

In the last part of the study, the researchers tested to see if the antiviral drug remdesivir inhibits virus infection in neurons and astrocytes.  They discovered that the drug was able to successfully reduce the viral level in astrocytes and prevent cell death.  For neurons, it was able to rescue them from steadily losing their function and even dying. 

The team says that the next steps to build on their findings is to continue studying the effects of the virus and better understand the role of ApoE4 in the brains of people who have COVID-19.  Many people that developed COVID-19 have recovered, but long-term neurological effects such as severe headaches are still being seen months after. 

“COVID-19 is a complex disease, and we are beginning to understand the risk factors involved in the manifestation of the severe form of the disease” says Dr. Arumugaswami.  “Our cell-based study provides possible explanation to why individuals with Alzheimer’s’ disease are at increased risk of developing COVID-19.”

The full results to this study were published in Cell Stem Cell.

Month of CIRM: Battling COVID-19

/ Kevin McCormack / Leave a comment

All this month we are using our blog and social media to highlight a new chapter in CIRM’s life, thanks to the people of California approving Proposition 14. We are looking back at what we have done since we were created in 2004, and also looking forward to the future.

Dr. John Zaia, City of Hope stem cell researcher

The news that effective vaccines have been developed to help fight COVID-19 was a truly bright spot at the end of a very dark year. But it will be months, in some countries years, before we have enough vaccines to protect everyone. That’s why it’s so important to keep pushing for more effective ways to help people who get infected with the virus.

One of those ways is in a clinical study that CIRM is funding with City of Hope’s Dr. John Zaia. Dr. Zaia and his team, in partnership with the Translational Genomics Research Institute (TGen) in Flagstaff, Arizona, are using something called convalescent plasma to try and help people who have contracted the virus. Here’s the website they have created for the study.

Plasma is a part of our blood that carries proteins, called antibodies, that help defend our bodies against viral infections. When a patient recovers from COVID-19, their blood plasma contains antibodies against the virus. The hope is that those antibodies can now be used as a potential treatment for COVID-19 to help people who are newly infected. 

To carry out the study they are using clinical trial sites around California, including some of the CIRM Alpha Stem Cell Network clinics.

For the study to succeed they’ll first need people who have recovered from the virus to donate blood. That’s particularly appropriate in January because this is National Volunteer Blood Donor Month.

The team has three elements to their approach:

  • A rapid-response screening program to screen potential COVID-19 convalescent plasma donors, particularly in underserved communities.
  • A laboratory center that can analyze the anti-SARS-CoV-2 antibodies properties in COVID-19 convalescent plasma.
  • An analysis of the clinical course of the disease in COVID-19 patients to identify whether antibody properties correlate with clinical benefit of COVID-19 convalescent plasma.

There’s reason to believe this approach might work. A study published this week in the New England Journal of Medicine, found that blood plasma from people who have recovered from COVID-19 can help older adults and prevent them from getting seriously ill with the virus if they get the plasma within a few days of becoming infected.

We are used to thinking of blood donations as being used to help people after surgery or who have been in an accident. In this study the donations serve another purpose, but one that is no less important. The World Health Organization describes blood as “the most precious gift that anyone can give to another person — the gift of life. A decision to donate your blood can save a life, or even several if your blood is separated into its components — red cells, platelets and plasma.”

That plasma could help in developing more effective treatments against the virus. Because until we have enough vaccines for everyone, we are still going to need as much help as we can get in fighting COVID-19. The recent surge in cases throughout the US and Europe are a reminder that this virus is far from under control. We have already lost far too many people. So, if you have recently recovered from the virus, or know someone who has, consider donating blood to this study. It could prove to be a lifesaver.

For more information about the study and how you can be part of it, click here.

UCLA scientists discover how SARS-CoV-2 causes multiple organ failure in mice

/ Yimy Villa / Leave a comment
Heart muscle cells in an uninfected mouse (left) and a mouse infected with SARS-CoV-2 (right) with mitochondria seen in pink. The disorganization of the cells and mitochondria in the image at right is associated with irregular heartbeat and death.
Image credit: UCLA Broad Stem Cell Center

As the worldwide coronavirus pandemic rages on, scientists are trying to better understand SARS-CoV-2, the virus that causes COVID-19, and the effects that it may have beyond those most commonly observed in the lungs. A CIRM-funded project at UCLA, co-led by Vaithilingaraja Arumugaswami, Ph.D. and Arjun Deb, M.D. discovered that SARS-CoV-2 can cause organ failure in the heart, kidney, spleen, and other vital organs of mice.

Mouse models are used to better understand the effects that a disease can have on humans. SARS-CoV-2 relies on a protein named ACE2 to infect humans. However, the virus doesn’t recognize the mouse version of the ACE2 protein, so healthy mice exposed to the SARS-CoV-2 virus don’t get sick.

To address this, past experiments by other research teams have genetically engineered mice to have the human version of the ACE2 protein in their lungs. These teams then infected the mice, through the nose, with the SARS-CoV-2 virus. Although this process led to viral infection in the mice and caused pneumonia, they don’t get as broad a range of other symptoms as humans do.

Previous research in humans has suggested that SARS-CoV-2 can circulate through the bloodstream to reach multiple organs. To evaluate this further, the UCLA researchers genetically engineered mice to have the human version of the ACE2 protein in the heart and other vital organs. They then infected half of the mice by injecting SARS-CoV-2 into their bloodstreams and compared them to mice that were not infected. The UCLA team tracked overall health and analyzed how levels of certain genes and proteins in the mice changed.

Within seven days, all of the mice infected with the virus had stopped eating, were completely inactive, and had lost an average of about 20% of their body weight. The genetically engineered mice that had not been infected with the virus did not lose a significant amount of weight. Furthermore, the infected mice had altered levels of immune cells, swelling of the heart tissue, and deterioration of the spleen. All of these are symptoms that have been observed in people who are critically ill with COVID-19.

What’s even more surprising is that the UCLA team also found that genes that help cells generate energy were shut off in the heart, kidney, spleen and lungs of the infected mice. The study also revealed that some changes were long-lasting throughout the organs in mice with SARS-CoV-2. Not only were genes turned off in some cells, the virus made epigenetic changes, which are chemical alterations to the structure of DNA that can cause more lasting effects. This might help explain why some people that have contracted COVID-19 have symptoms for weeks or months after they no longer have traces of the virus in their body.

In a UCLA press release, Dr. Deb discusses the importance and significance of their findings.

“This mouse model is a really powerful tool for studying SARS-CoV-2 in a living system. Understanding how this virus can hijack our cells might eventually lead to new ways to prevent or treat the organ failure that can accompany COVID-19 in humans.”

The full results of this study were published in JCI Insight.

One shot, two benefits!

/ Kevin McCormack / 2 Comments
Doctor preparing an influenza vaccine for a patient.

To try and boost sales during the pandemic many businesses are offering two-for-one deals; buy one product get another free. Well, that might also be the case with a flu shot; get one jab and get protection from two viruses.

A new study offers an intriguing – though not yet certain – suggestion that getting a flu shot could not only reduce your risk of getting the flu, but also help reduce your risk of contracting the coronavirus. If it’s true it would be a wonderful tool for health professionals hoping to head of a twindemic of flu and COVID-19 this winter. It would also be a pretty sweet deal for the rest of us.

Researchers at Radboud University Medical Center in the Netherlands looked through their hospital’s database and compared people who got a flu shot during the previous year with people who didn’t. They found that people who got the vaccine were 39 percent less likely to have tested positive for the coronavirus than people who didn’t get the vaccine.

Now, there are a bunch of caveats about this study (published in the preprint journal MedRxiv) one of which is that it wasn’t peer reviewed. Another is that people who get flu shots might just be more health conscious than people who don’t, which means they might also be more aware of the need to wear a mask, social distance, wash their hands etc.

But that doesn’t mean this study is wrong. Two recent studies (in the journal Vaccines and the Journal of Medical Virology) also found similar findings, that people over the age of 65 who got a flu shot had a lower risk of getting COVID-19. That’s particularly important for that age group as they are the ones most likely to experience life-threatening complications from COVID-19.

But what could explain getting a two-fer from one vaccine? Well, there’s a growing body of research that points to something called “trained innate immunity”. Our bodies have two different kinds of immune system, adaptive and innate. Vaccines activate the adaptive system, causing it to develop antibodies to attack and kill a virus. But there’s also evidence these same vaccines could trigger our innate immune system to help fight off infections. So, a flu vaccine could boost your adaptive immunity against the flu, but also kick in the innate immunity against the coronavirus.

In an article in Scientific American, Ellen Foxman, an immunobiologist and clinical pathologist at the Yale School of Medicine, says that might be the case here: “There is evidence from the literature that trained immunity does exist and can offer broad protection, in unexpected ways, against other pathogens besides what the vaccine was designed against.”

The researchers in the Netherlands wanted to see if there was any evidence that what they saw in their hospital had any basis in fact. So, they devised a simple experiment. They took blood cells from healthy individuals and exposed some of the cells to the flu vaccine. After six days they exposed all the cells to the SARS-CoV-2, the virus that causes COVID-19.

Compared to the untreated cells, the cells that had been exposed to the flu vaccine produced more virus-fighting immune molecules called cytokines. These can attack the virus and help protect people early on, resulting in a milder, less dangerous infection.

All in all it’s encouraging evidence that a flu shot might help protect you against the coronavirus. And at the very least it will reduce your risk of the flu, and if there’s one thing you definitely don’t want this year it’s having to battle two life-threatening viruses at the same time.

Want to help us solve a mystery?

/ Kevin McCormack / 1 Comment
Patient that has recovered from Covid-19 donating blood plasma. Photo courtesy Science Photo

Convalescent plasma has been in the news a lot lately as a potential treatment for people infected with the coronavirus. In August the US Food and Drug Administration (FDA) granted emergency use authorization (EUA) to use these products based on preliminary data that suggested it might help people battling COVID. But there are still a lot of unanswered questions about this approach.

And that’s where you come in.

Plasma is a component of blood that carries proteins called antibodies that are usually involved in defending our bodies against viral infections.  We also know that blood plasma from patients that have recovered from COVID-19, referred to as convalescent plasma, contain antibodies against the virus that can be used as a potential treatment for COVID-19. 

That’s the theory, but the reality is that there are still a lot we don’t know, basic questions such as does it really work, how does it work, does it work for everyone or just some patients? A clinical  grant includes testing the plasma in COVID-19 Positive patients that CIRM is funding with City of Hope, UC Irvine and Translational Genomics Research Institute (TGen) hopes to answer those questions. 

The first step is getting the plasma from people who have recovered from COVID and then testing it to make sure it’s safe and to identify what blood type it is, so you can match that blood type with the person receiving it.

But plasma doesn’t contain just one kind of antibody, there are many antibodies and each one works in a slightly different way. For example, two antibodies, IGM and IGG, target in on the spike protein on the coronavirus. The goal is to block that spike and prevent the virus from spreading throughout the body. IGM has up to 10 ‘arms’ and so has the potential to bind multiple copies of the spike, whereas IGG has only 2 arms, but lasts longer. Both IGM and IGG also come in many different flavors, allowing them to bind to many different parts of the spike, some being more protective than others.

That’s one of the things that this trial is trying to find out. And you can help them do that. The trial needs volunteers, volunteers to donate the plasma and volunteers to try the therapy.

The team is evaluating changes that occur before and after plasma treatment.  Many recipients have no immediate response, a few get dramatically better, and some continue to have symptoms long after discharge from the hospital.  These so-called “long-haulers” can have debilitating problems, months after becoming infected. The study hopes to evaluate these variable responses to plasma treatment.

But more people are needed if we are to truly understand what works best. We need people who are newly infected, those being treated with plasma, and those that have recovered from the virus.

We are particularly interested in recruiting people from the Black and Latinx communities, groups that are often underserved when it comes to access to medical care.

The team has created a website to make it easy to find out more about the clinical trial, and to see if you are a good candidate to be part of it, either as a donor or recipient.

Lives are at stake and time is short so join us, help us find answers to the most pressing medical issue of our times. It’s a chance to do something that might benefit your family, your friends and your community.

Cures, clinical trials and unmet medical needs

/ Kevin McCormack / Leave a comment

When you have a great story to tell there’s no shame in repeating it as often as you can. After all, not everyone gets to hear first time around. Or second or third time. So that’s why we wanted to give you another opportunity to tune into some of the great presentations and discussions at our recent CIRM Alpha Stem Cell Clinic Network Symposium.

It was a day of fascinating science, heart-warming, and heart-breaking, stories. A day to celebrate the progress being made and to discuss the challenges that still lie ahead.

There is a wide selection of topics from “Driving Towards a Cure” – which looks at some pioneering work being done in research targeting type 1 diabetes and HIV/AIDS – to Cancer Clinical Trials, that looks at therapies for multiple myeloma, brain cancer and leukemia.

The COVID-19 pandemic also proved the background for two detailed discussions on our funding for projects targeting the coronavirus, and for how the lessons learned from the pandemic can help us be more responsive to the needs of underserved communities.

Here’s the agenda for the day and with each topic there’s a link to the video of the presentation and conversation.

Thursday October 8, 2020

View Recording: CIRM Fellows Trainees

9:00am Welcome Mehrdad Abedi, MD, UC Davis Health, ASCC Program Director  

Catriona Jamieson, MD,  View Recording: ASCC Network Value Proposition

9:10am Session I:  Cures for Rare Diseases Innovation in Action 

Moderator: Mark Walters, MD, UCSF, ASCC Program Director 

Don Kohn, MD, UCLA – View Recording: Severe combined immunodeficiency (SCID) 

Mark Walters, MD, UCSF, ASCC Program Director – View Recording: Thalassemia 

Pawash Priyank, View Recording: Patient Experience – SCID

Olivia and Stacy Stahl, View Recording: Patient Experience – Thalassemia

10 minute panel discussion/Q&A 

BREAK

9:55am Session II: Addressing Unmet Medical Needs: Driving Towards a Cure 

Moderator: John Zaia, MD, City of Hope, ASCC Program Direction 

Mehrdad Abedi, MD, UC Davis Health, ASCC Program Director – View Recording: HIV

Manasi Jaiman, MD, MPH, ViaCyte, Vice President, Clinical Development – View Recording: Diabetes

Jeff Taylor, Patient Experience – HIV

10 minute panel discussion/Q&A 

BREAK

10:40am Session III: Cancer Clinical Trials: Networking for Impact 

Moderator: Catriona Jamieson, MD, UC San Diego, ASCC Program Director 

Daniela Bota, MD, PhD, UC Irvine, ASCC Program Director – View Recording:  Glioblastoma 

Michael Choi, MD, UC San Diego – View Recording: Cirmtuzimab

Matthew Spear, MD, Poseida Therapeutics, Chief Medical Officer – View Recording: Multiple Myeloma  

John Lapham, Patient Experience –  View Recording: Chronic lymphocytic leukemia (CLL) 

10 minute panel discussion/Q&A 

BREAK

11:30am Session IV: Responding to COVID-19 and Engaging Communities

Two live “roundtable conversation” sessions, 1 hour each.

Roundtable 1: Moderator Maria Millan, MD, CIRM 

CIRM’s / ASCC Network’s response to COVID-19 Convalescent Plasma, Cell Therapy and Novel Vaccine Approaches

Panelists

Michael Matthay, MD, UC San Francisco: ARDS Program

Rachael Callcut, MD, MSPH, FACS, UC Davis: ARDS Program 

John Zaia, MD, City of Hope: Convalescent Plasma Program 

Daniela Bota, MD, PhD, UC Irvine: Natural Killer Cells as a Treatment Strategy 

Key questions for panelists: 

  • Describe your trial or clinical program?
  • What steps did you take to provide access to disproportionately impacted communities?
  • How is it part of the overall scientific response to COVID-19? 
  • How has the ASCC Network infrastructure accelerated this response? 

Brief Break

Roundtable 2: Moderator Ysabel Duron, The Latino Cancer Institute and Latinas Contra Cancer

View Recording: Roundtable 2

Community Engagement and Lessons Learned from the COVID Programs.  

Panelists

Marsha Treadwell, PhD, UC San Francisco: Community Engagement  

Sheila Young, MD, Charles R. Drew University of Medicine and Science: Convalescent Plasma Program in the community

David Lo, MD, PhD,  UC Riverside: Bringing a public health perspective to clinical interventions

Key questions for panelists: 

  • What were important lessons learned from the COVID programs? 
  • How can CIRM and the ASCC Network achieve equipoise among communities and engender trust in clinical research? 
  • How can CIRM and the ASCC Network address structural barriers (e.g. job constrains, geographic access) that limit opportunities to participate in clinical trials?

Partners in health

/ Kevin McCormack / 2 Comments
From left to right: Heather Dahlenburg, Jan Nolta, Jeannine Logan White, Sheng Yang
From left to right: Heather Dahlenburg, staff research associate; Jan Nolta, director of the Stem Cell Program; Jeannine Logan White, advanced cell therapy project manager; Sheng Yang, graduate student, Bridges Program, Humboldt State University, October 18, 2019. (AJ Cheline/UC Davis)

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.

In 2016, led by Fred Meyers, a professor in the School of Medicine, UC Davis launched the Center for Precision Medicine and Data Sciences, bringing together innovations such as genomics and biomedical data sciences to create individualized treatments for patients.

Last year, the university launched the Gene Therapy Center, part of the IMPACT Center program.

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.

Several cell and gene therapies have progressed to the point that ongoing clinical trials are being conducted at UC Davis for diseases, including sickle-cell anemia, retinopathy, muscle injury, dysphasia, advanced cancer, and Duchenne muscular dystrophy, among others.

“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.

.Joseph Anderson

Joseph Anderson

“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

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.

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.

Battling COVID and turning back the clock on stem cell funding

/ Kevin McCormack / 5 Comments
Coronavirus

Battling the virus that causes COVID-19 is something that is top of everyone’s mind right now. That’s why CIRM is funding 17 different projects targeting the virus. But one of the most valuable tools in helping develop vaccines against a wide variety of diseases in the past is now coming under threat. We’ll talk about both issues in a live broadcast we’re holding on Wednesday, October 14th at noon (PDT).

That date is significant because it’s Stem Cell Awareness Day and we thought it appropriate to host a meeting looking at two of the most important issues facing the field.

The first part of the event will focus on the 17 projects that CIRM is funding that target COVID-19. This includes three clinical trials aiming to treat people who have been infected with the virus and are experiencing some of the more severe effects, such as damaged lungs.

We’ll also look at some of the earlier stage research that includes:

  • Work to help develop a vaccine
  • Using muscle stem cells to help repair damage to the diaphragm in patients who have spent an extended period on a ventilator
  • Boosting immune system cells to help fight the virus

The second part of the event will look at ways that funding for stem cell research at the federal level is once again coming into question. The federal government has already imposed new restrictions on funding for fetal tissue research, and now there are efforts in Congress to restrict funding for embryonic stem cell research.

The impacts could be significant. Fetal tissue has been used for decades to help develop some of the most important vaccines used today including rubella, chickenpox, hepatitis A, and shingles. They have also been used to make approved drugs against diseases including hemophilia, rheumatoid arthritis, and cystic fibrosis.

We’ll look at some of the reasons why we are seeing these potential restrictions on the medical research and what impact they could have on the ability to develop new treatments for the coronavirus and other deadly diseases.

You can watch the CIRM Stem Cell Awareness Day live event by going here: https://www.youtube.com/c/CIRMTV/videos at noon on Wednesday, October 14th.

Feel free to share news about this event with anyone you think might be interested.

We look forward to seeing you there.