Explaining COVID can be a pitch

When people ask me what I do at CIRM I sometimes half-jokingly tell them that I’m the official translator: I take complex science and turn it into everyday English. That’s important. The taxpayers of California have a right to know how their money is being spent and how it might benefit them. But that message can be even more effective when it comes from the scientists themselves.

Recently we asked some of the scientists we are funding to do research into COVID-19 to record what’s called an “elevator pitch”. This is where they prepare an explanation of their work that is in ordinary English and is quite short, short enough to say it to someone as you ride in an elevator. Hence the name.

It sounds easy enough. But it’s not. When you are used to talking in the language of science day in and day out, suddenly switching codes to talk about your work in plain English can take some practice. Also, you have spent years, often decades, on this work and to have to explain it in around one minute is no easy thing.

But our researchers rose to the challenge. Here’s some examples of just how well they did.

Charting a new course for stem cell research

What are the latest advances in stem cell research targeting cancer? Can stem cells help people battling COVID-19 or even help develop a vaccine to stop the virus? What are researchers and the scientific community doing to help address the unmet medical needs of underserved communities? Those are just a few of the topics being discussed at the Annual CIRM Alpha Stem Cell Clinic Network Symposium on Thursday, October 8th from 9am to 1.30pm PDT.

Like pretty nearly everything these days the symposium is going to be a virtual event, so you can watch it from the comfort of your own home on a phone or laptop. And it’s free.

The CIRM Alpha Clinics are a network of leading medical centers here in California. They specialize in delivering stem cell and gene therapies to patients. So, while many conferences look at the promise of stem cell therapies, here we deal with the reality; what’s in the clinic, what’s working, what do we need to do to help get these therapies to patients in need?

It’s a relatively short meeting, with short presentations, but that doesn’t mean it will be short on content. Some of the best stem cell researchers in the U.S. are taking part so you’ll learn an awful lot in a short time.

We’ll hear what’s being done to find therapies for

  • Rare diseases that affect children
  • Type 1 diabetes
  • HIV/AIDS
  • Glioblastoma
  • Multiple myeloma

We’ll discuss how to create a patient navigation system that can address social and economic determinants that impact patient participation? And we’ll look at ways that the Alpha Clinic Network can partner with community care givers around California to increase patient access to the latest therapies.

It’s going to be a fascinating day. And did I mention it’s free!

All you have to do is go to this Eventbrite page to register.

And feel free to share this with your family, friends or anyone you think might be interested.

We look forward to seeing you there.

CIRM & CZI & MOU for COVID-19

Too many acronyms? Not to worry. It is all perfectly clear in the news release we just sent out about this.

A new collaboration between the California Institute for Regenerative Medicine (CIRM) and the Chan Zuckerberg Initiative (CZI) will advance scientific efforts to respond to the COVID-19 pandemic by collaborating on disseminating single-cell research that scientists can use to better understand the SARS-CoV-2 virus and help develop treatments and cures.

CIRM and CZI have signed a Memorandum of Understanding (MOU) that will combine CIRM’s infrastructure and data collection and analysis tools with CZI’s technology expertise. It will enable CIRM researchers studying COVID-19 to easily share their data with the broader research community via CZI’s cellxgene tool, which allows scientists to explore and visualize measurements of how the virus impacts cell function at a single-cell level. CZI recently launched a new version of cellxgene and is supporting the single-cell biology community by sharing COVID-19 data, compiled by the global Human Cell Atlas effort and other related efforts, in an interactive and scalable way.

“We are pleased to be able to enter into this partnership with CZI,” said Dr. Maria T. Millan, CIRM’s President & CEO. “This MOU will allow us to leverage our respective investments in genomics science in the fight against COVID-19. CIRM has a long-standing commitment to generation and sharing of sequencing and genomic data from a wide variety of projects. That’s why we created the CIRM genomics award and invested in the Stem Cell Hub at the University of California, Santa Cruz, which will process the large complex datasets in this collaboration.”  

“Quickly sharing scientific data about COVID-19 is vital for researchers to build on each other’s work and accelerate progress towards understanding and treating a complex disease,” said CZI Single-Cell Biology Program Officer Jonah Cool. “We’re excited to partner with CIRM to help more researchers efficiently share and analyze single-cell data through CZI’s cellxgene platform.”

In March 2020, the CIRM Board approved $5 million in emergency funding to target COVID-19. To date, CIRM has funded 17 projects, some of which are studying how the SARS-CoV-2 virus impacts cell function at the single-cell level.

Three of CIRM’s early-stage COVID-19 research projects will plan to participate in this collaborative partnership by sharing data and analysis on cellxgene.   

  • Dr. Evan Snyder and his team at Sanford Burnham Prebys Medical Discovery Institute are using induced pluripotent stem cells (iPSCs), a type of stem cell that can be created by reprogramming skin or blood cells, to create lung organoids. These lung organoids will then be infected with the novel coronavirus in order to test two drug candidates for treating the virus.
  • Dr. Brigitte Gomperts at UCLA is studying a lung organoid model made from human stem cells in order to identify drugs that can reduce the number of infected cells and prevent damage in the lungs of patients with COVID-19.
  • Dr. Justin Ichida at the University of Southern California is trying to determine if a drug called a kinase inhibitor can protect stem cells in the lungs and other organs, which the novel coronavirus selectively infects and kills.

“Cumulative data into how SARS-CoV-2 affects people is so powerful to fight the COVID-19 pandemic,” said Stephen Lin, PhD, the Senior CIRM Science Officer who helped develop the MOU. “We are grateful that the researchers are committed to sharing their genomic data with other researchers to help advance the field and improve our understanding of the virus.”

CZI also supports five distinct projects studying how COVID-19 progresses in patients at the level of individual cells and tissues. This work will generate some of the first single-cell biology datasets from donors infected by SARS-CoV-2 and provide critical insights into how the virus infects humans, which cell types are involved, and how the disease progresses. All data generated by these grants will quickly be made available to the scientific community via open access datasets and portals, including CZI’s cellxgene tool.

CIRM partners with UCLA scientists to take on COVID-19

Don’t you love it when someone does your job for you and does it so well you have no need to add anything to it! Doesn’t happen very often – sad to say – but this week our friends at UCLA wrote a great article describing the work they are doing to target COVID-19. Best of all, all the work described is funded by CIRM. So read, and enjoy.

Two scientists in a lab at the UCLA Broad Stem Cell Research Center

By Tiare Dunlap, UCLA

As the COVID-19 pandemic rages on, UCLA researchers are rising to the occasion by channeling their specialized expertise to seek new and creative ways to reduce the spread of the virus and save lives. Using years’ — or even decades’ — worth of knowledge they’ve acquired studying other diseases and biological processes, many of them have shifted their focus to the novel coronavirus, and they’re collaborating across disciplines as they work toward new diagnostic tests, treatments and vaccines.

At UCLA, more than 230 research projects, including several being led by members of the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA, are contributing to that mission.

Dr. Brititte Gomperts, Photo courtesy UCLA

“As a result of the pandemic, everyone on campus is committed to finding ways that their unique expertise can help out,” said Dr. Brigitte Gomperts, professor and vice chair of research in pediatric hematology-oncology and pulmonary medicine at the David Geffen School of Medicine at UCLA and a member of the UCLA Children’s Discovery and Innovation Institute. “So many of my colleagues have repurposed their labs to work on the virus. It’s very seldom that you have one thing that everybody’s working on, and it has been truly inspiring to see how everyone has come together to try and solve this.”

Here’s a look at five projects in which UCLA scientists are using stem cells — which can self-replicate and give rise to all cell types — to take on COVID-19.

Using lung organoids as models to test possible treatments 

Dr. Brigitte Gomperts

Gomperts has spent years perfecting methods for creating stem cell–derived three-dimensional lung organoids. Now, she’s using those organoids to study how SARS-CoV-2, the virus that causes COVID-19, affects lung tissue and to rapidly screen thousands of prospective treatments. Because the organoids are grown from human cells and reflect the cell types and architecture of the lungs, they can offer unprecedented insights into how the virus infects and damages the organ.  

Gomperts is collaborating with UCLA colleagues Vaithilingaraja Arumugaswami, a virologist, and Robert Damoiseaux, an expert in molecular screening. Their goal is to find an existing therapy that could be used to reduce the spread of infection and associated damage in the lungs.

“We’re starting with drugs that have already been tested in humans because our goal is to find a therapy that can treat patients with COVID-19 as soon as possible,” Gomperts said. Read more.

Repurposing a cancer therapy

Dr. Vaithi Arumugaswami: Photo courtesy UCLA

Vaithilingaraja Arumugaswami, associate professor of molecular and medical pharmacology at the Geffen School of Medicine

In addition to collaborating with Gomperts, Arumugaswami and Damoiseaux identified the cancer drug Berzosertib as a possible treatment for COVID-19 after screening 430 drug candidates. The drug, which is currently being tested in clinical trials for cancer, works by blocking a DNA repair process that is exploited by solid cancers and the SARS-CoV-2 virus, and the UCLA scientists found that it is very effective at limiting viral replication and cell death. 

“Clinical trials have shown that Berzosertib blocks the DNA repair pathway in cancer cells, but has no effects on normal, healthy cells,” Arumugaswami said.

Now, Arumugaswami and Gustavo Garcia Jr., a staff research associate, are testing Berzosertib and additional drug combinations on lung organoids developed in Gomperts’ lab and stem cell–derived heart cells infected with SARS-CoV-2. They suspect that if the drug is administered soon after diagnosis, it could limit the spread of infection and prevent complications. Read more.

Studying the immune response to the virus

Dr. Gay Crooks

Dr. Gay Crooks, professor of pathology and laboratory medicine and of pediatrics at the Geffen School of Medicine, and co-director of the Broad Stem Cell Research Center; and Dr. Christopher Seet,  

assistant professor of hematology-oncology at the Geffen School of Medicine

Crooks and Seet are using stem cells to model how immune cells recognize and fight the virus in a lab dish. To do that, they’re infecting blood-forming stem cells — which can give rise to all blood and immune cells — from healthy donors with parts of the SARS-CoV-2 virus and then coaxing the stem cells to produce immune cells called dendritic cells. Dendritic cells devour viral proteins, chop them up into pieces and then present those pieces to other immune cells called T cells to provoke a response.

By studying that process, Crooks and Seet hope to identify which parts of the virus provoke the strongest T-cell responses. Developing an effective vaccine for SARS-CoV-2 will require a deep understanding of how the immune system responds to the virus, and this work could be an important step in that direction, giving researchers and clinicians a way to gauge the effectiveness of possible vaccines.

“When we started developing this project some years ago, we had no idea it would be so useful for studying a viral infection — any viral infection,” Crooks said. “It was only because we already had these tools in place that we could spring into action so fast.” Read more.

Developing a booster that could help a vaccine last longer

Song Li, chair and professor of bioengineering at the UCLA Samueli School of Engineering

A COVID-19 vaccine will need to provide long-term protection from infection. But how long a vaccine protects from infection isn’t solely dependent on the vaccine.

The human body relies on long-living immune cells called T memory stem cells that guard against pathogens such as viruses and bacteria that the body has encountered before. Unfortunately, the body’s capacity to form T memory stem cells decreases with age. So no matter how well designed a vaccine is, older adults who don’t have enough of a response from T memory stem cells will not be protected long-term.

To address that issue, Li is developing an injectable biomaterial vaccine booster that will stimulate the formation of T memory stem cells. The booster is made up of engineered materials that release chemical messengers to stimulate the production of T memory stem cells. When combined with an eventual SARS-CoV-2 vaccine, they would prompt the body to produce immune cells primed to recognize and eliminate the virus over the long term.

“I consider it my responsibility as a scientist and an engineer to translate scientific findings into applications to help people and the community,” Li said. Read more.

Creating an off-the-shelf cell therapy

Lili Yang, associate professor of microbiology, immunology and molecular genetics in the UCLA College

Invariant natural killer T cells, or iNKT cells, are the special forces of the immune system. They’re extremely powerful and can immediately recognize and respond to many different intruders, from infections to cancer.

Yang is testing whether iNKT cells would make a particularly effective treatment for COVID-19 because they have the capacity to kill virally infected cells, offer protection from reinfection and rein in the excessive inflammation caused by a hyperactive immune response to the virus, which is thought to be a major cause of tissue damage and death in people with the disease.

One catch, though, is that iNKT cells are incredibly scarce: One drop of human blood contains around 10 million blood cells but only around 10 iNKT cells. That’s where Yang’s research comes in. Over the past several years, she has developed a method for generating large numbers of iNKT cells from blood-forming stem cells. While that work was aimed at creating a treatment for cancer, Yang’s lab has adapted its work over the past few months to test how effective stem cell–derived iNKT cells could be in fighting COVID-19. With her colleagues, she has been studying how the cells work in fighting the disease in models of SARS-CoV-2 infection that are grown from human kidney and lung cells.

“My lab has been developing an iNKT cell therapy for cancer for years,” Yang said. “This means a big part of the work is already done. We are repurposing a potential therapy that is very far along in development to treat COVID-19.” Read more.

“Our center is proud to join CIRM in supporting these researchers as they adapt projects that have spent years in development to meet the urgent need for therapies and vaccines for COVID-19,” said Dr. Owen Witte, founding director of the UCLA Broad Stem Cell Research Center. “This moment highlights the importance of funding scientific research so that we may have the foundational knowledge to meet new challenges as they arise.” Crooks, Gomperts, Seet and Yang are all members of the UCLA Jonsson Comprehensive Cancer Center. Damoiseaux is a professor of molecular and medical pharmacology and director of the Molecular Shared Resource Center at the California NanoSystems Institute at UCLA

Stem cells used to look at how COVID-19 attacks heart muscle

Human induced pluripotent stem cell-derived cardiomyocytes (heart cells) shown in green and blue, are infected by the novel coronavirus SARS-CoV-2 (red). Image provided by Cedars-Sinai Board of Governors Regenerative Medicine Institute.

There is still a lot that we don’t understand about SARS-CoV-2 (COVID-19), the new coronavirus that has caused a worldwide pandemic. Some patients that contract the virus experiences heart problems, but the reasons are not entirely clear. Pre-existing heart conditions or inflammation and oxygen deprivation that result from COVID-19 have all been implicated but more evidence needs to be collected.

To evaluate this, a joint study between Cedars-Sinai Board of Governors Regenerative Medicine Institute and the UCLA Broad Stem Cell Research Center used human induced pluripotent stem cells (iPSCs), a kind of stem cell that can become any kind of cell in the body and is usually made from skin cells. The iPSCS were converted into heart cells and infected with COVID-19 in order to study the effects of the virus.

The results of this study showed that the iPSC-derived heart cells are susceptible to COVID-19 infection and that the virus can quickly divide inside the heart cells. Furthermore, the infected heart cells showed changes in their ability to beat 72 hours after infection.

In a press release, Dr. Clive Svendsen, senior and co-corresponding author of the study and director of the Cedars-Sinai Board of Governors Regenerative Medicine Institute, elaborated on the results.

“This viral pandemic is predominately defined by respiratory symptoms, but there are also cardiac complications, including arrhythmias, heart failure and viral myocarditis. While this could be the result of massive inflammation in response to the virus, our data suggest that the heart could also be directly affected by the virus in COVID-19.”

Although this study does not perfectly replicate the conditions inside the human body, the iPSC heart cells may also help identify and screen new potential drugs that could alleviate viral infection of the heart.

The research team has already found that treatment with an antibody called ACE2 was able to decrease viral replication on the iPSC heart cells.

In the same press release Dr. Arun Sharma, first author and another co-corresponding author of the study and a research fellow at the Cedars-Sinai Board of Governors Regenerative Medicine Institute, had this to say about the ACE2 antibody.

“By blocking the ACE2 protein with an antibody, the virus is not as easily able to bind to the ACE2 protein, and thus cannot easily enter the cell. This not only helps us understand the mechanisms of how this virus functions, but also suggests therapeutic approaches that could be used as a potential treatment for SARS-CoV-2 infection.”

The study’s third co-corresponding author was Dr. Vaithilingaraja Arumugaswami, an associate professor of molecular and medical pharmacology at the David Geffen School of Medicine at UCLA and member of the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research.

The full results of this study were published in Cell Reports Medicine.

A ready-made approach to tackling COVID-19

Coronavirus particles, illustration.

In late March the CIRM Board approved $5 million in emergency funding for COVID-19 research. The idea was to support great ideas from California’s researchers, some of which had already been tested for different conditions, and see if they could help in finding treatments or a vaccine for the coronavirus.

Less than a month later we were funding a clinical trial and two other projects, one that targeted a special kind of immune system cell that has the potential to fight the virus.

Our friends at UCLA have just written a terrific piece on this project and the team that came up with the idea. Here is that article.

Researchers use stem cells to model the immune response to COVID-19

By Tiare Dunlap

Cities across the United States are opening back up, but we’re still a long way from making the COVID-19 pandemic history. To truly accomplish that, we need to have a vaccine that can stop the spread of infection.

But to develop an effective vaccine, we need to understand how the immune system responds to SARS-CoV-2, the virus that causes COVID-19.

Vaccines work by imitating infection. They expose a person’s immune system to a weakened version or component of the virus they are intended to protect against. This essentially prepares the immune system to fight the virus ahead of time, so that if a person is exposed to the real virus, their immune system can quickly recognize the enemy and fight the infection. Vaccines need to contain the right parts of the virus to provoke a strong immune response and create long-term protection.

Most of the vaccines in development for SARS CoV-2 are using part of the virus to provoke the immune system to produce proteins called antibodies that neutralize the virus. Another way a vaccine could create protection against the virus is by activating the T cells of the immune system.

T cells specifically “recognize” virus-infected cells, and these kinds of responses may be especially important for providing long-term protection against the virus. One challenge for researchers is that they have only had a few months to study how the immune system protects against SARS CoV-2, and in particular, which parts of the virus provoke the best T-cell responses.

This is where immunotherapy researchers and UCLA Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research members Dr. Gay Crooks and Dr. Christopher Seet come in.

Dr. Gay Crooks: Photo courtesy UCLA

For years, they have been perfecting an innovative technology that uses blood-forming stem cells — which can give rise to all types of blood and immune cells — to produce a rare and powerful subset of immune cells called type 1 dendritic cells. Type 1 dendritic cells play an essential role in the immune response by devouring foreign proteins, termed antigens, from virus-infected cells and then chopping them into fragments. Dendritic cells then use these protein fragments to trigger T cells to mount an immune response.

Dr. Christopher Seet: Photo courtesy UCLA

Using this technology, Crooks and Seet are working to pinpoint which specific parts of the SARS-CoV-2 virus provoke the strongest T-cell responses.

Building long-lasting immunity

“We know from a lot of research into other viral infections and also in cancer immunotherapy, that T-cell responses are really important for long-lasting immunity,” said Seet, an assistant professor of hematology-oncology at the David Geffen School of Medicine at UCLA. “And so this approach will allow us to better characterize the T-cell response to SARS-CoV-2 and focus vaccine and therapeutic development on those parts of the virus that induce strong T-cell immunity.”

This project was recently awarded $150,000 from the California Institute for Regenerative Medicine, the state’s stem cell agency. The award was matched by the UCLA Broad Stem Cell Research Center.

Crooks’ and Seet’s project uses blood-forming stem cells taken from healthy donors and infected with a virus containing antigens from SARS-CoV-2. They then direct these stem cells to produce large numbers of type 1 dendritic cells using a new method developed by Seet and Suwen Li, a graduate student in Crooks’ lab. Both Seet and Li are graduates of the UCLA Broad Stem Cell Research Center’s training program.

“The dendritic cells we are able to make using this process are really good at chopping up viral antigens and eliciting strong immune responses from T cells,” said Crooks, a professor of pathology and laboratory medicine and of pediatrics at the medical school and co-director of the UCLA Broad Stem Cell Research Center.

When type 1 dendritic cells chop up viral antigens into fragments, they present these fragments on their cell surfaces to T cells. Our bodies produce millions and millions of T cells each day, each with its own unique antigen receptor, however only a few will have a receptor capable of recognizing a specific antigen from a virus.

When a T cell with the right receptor recognizes a viral antigen on a dendritic cell as foreign and dangerous, it sets off a chain of events that activates multiple parts of the immune system to attack cells infected with the virus. This includes clonal expansion, the process by which each responding T cell produces a large number of identical cells, called clones, which are all capable of recognizing the antigen.

“Most of those T cells will go off and fight the infection by killing cells infected with the virus,” said Seet, who, like Crooks, is also a member of the UCLA Jonsson Comprehensive Cancer Center. “However, a small subset of those cells become memory T cells — long-lived T cells that remain in the body for years and protect from future infection by rapidly generating a robust T-cell response if the virus returns. It’s immune memory.”

Producing extremely rare immune cells

This process has historically been particularly challenging to model in the lab, because type 1 dendritic cells are extremely rare — they make up less than 0.1% of cells found in the blood. Now, with this new stem cell technology, Crooks and Seet can produce large numbers of these dendritic cells from blood stem cells donated by healthy people, introduce them to parts of the virus, then see how T cells  taken from the blood can respond in the lab. This process can be repeated over and over using cells taken from a wide range of healthy people.

“The benefit is we can do this very quickly without the need for an actual vaccine trial, so we can very rapidly figure out in the lab which parts of the virus induce the best T-cell responses across many individuals,” Seet said.

The resulting data could be used to inform the development of new vaccines for COVID-19 that improve T-cell responses. And the data about which viral antigens are most important to the T cells could also be used to monitor the effectiveness of existing vaccine candidates, and an individual’s immune status to the virus.

“There are dozens of vaccine candidates in development right now, with three or four of them already in clinical trials,” Seet said. “We all hope one or more will be effective at producing immediate and long-lasting immunity. But as there is so much we don’t know about this new virus, we’re still going to need to really dig in to understand how our immune systems can best protect us from infection.”

Supporting basic research into our body’s own processes that can inform new strategies to fight disease is central to the mission of the Broad Stem Cell Research Center.

“When we started developing this project some years ago, we had no idea it would be so useful for studying a viral infection, any viral infection,” Crooks said. “And it was only because we already had these tools in place that we could spring into action so fast.”

Scientists Engineer Stem Cells to Fight HIV

Image of the virus that causes AIDS – courtesy NIH

If that headline seems familiar it should. It came from an article in MIT Technology Review back in 2009. There have been many other headlines since then, all on the same subject, and yet here we are, in 2020, and still no cure for HIV/AIDS. So what’s the problem, what’s holding us back?

First, the virus is incredibly tough and wily. It is constantly mutating so trying to target it is like playing a game of ‘whack a mole’. Secondly not only can the virus evade our immune system, it actually hijacks it and uses it to help spread itself throughout the body. Even new generations of anti-HIV medications, which are effective at controlling the virus, can’t eradicate it. But now researchers are using new tools to try and overcome those obstacles and tame the virus once and for all.

Dr. Scott Kitchen: Photo David Geffen School of Medicine, UCLA

UCLA researchers Scott Kitchen and Irvin Chen have been awarded $13.65 million by the National Institutes of Health (NIH) to see if they can use the patient’s own immune system to fight back against HIV.

Dr. Irvin Chen: Photo UCLA

Dr. Kitchen and Dr. Chen take the patient’s own blood-forming stem cells and then, in the lab, they genetically engineer them to carry proteins called chimeric antigen receptors or CARs. Once these blood cells are transplanted back into the body, they combine with the patient’s own immune system T cells (CAR T). These T cells now have a newly enhanced ability to target and destroy HIV.

That’s the theory anyway. Lots of research in the lab shows it can work. For example, the UCLA team recently showed that these engineered CAR T cells not only destroyed HIV-infected cells but also lived for more than two years. Now the team at UCLA want to take the lessons learned in the lab and apply them to people.

In a news release Dr. Kitchen says the NIH grant will give them a terrific opportunity to do that: “The overarching goal of our proposed studies is to identify a new gene therapy strategy to safely and effectively modify a patient’s own stem cells to resist HIV infection and simultaneously enhance their ability to recognize and destroy infected cells in the body in hopes of curing HIV infection. It is a huge boost to our efforts at UCLA and elsewhere to find a creative strategy to defeat HIV.”

By the way, CIRM helped get this work off the ground with an early-stage grant. That enabled Dr. Kitchen and his team to get the data they needed to be able to apply to the NIH for this funding. It’s a great example of how we can kick-start projects that no one else is funding. You can read a blog about that early stage research here.

CIRM has already funded three clinical trials targeting HIV/AIDS. Two of these are still active; Dr. Mehrdad Abedi at UC Davis and Dr. John Zaia at City of Hope.

Promising results from CIRM-funded projects

Severe Leukocyte Adhesion Deficiency-1 (LAD-1) is a rare condition that causes the immune system to malfunction and reduces its ability to fight off viruses and bacteria. Over time the repeated infections can take a heavy toll on the body and dramatically shorten a person’s life. But now a therapy, developed by Rocket Pharmaceuticals, is showing promise in helping people with this disorder.

The therapy, called RP-L201, targets white blood cells called neutrophils which ordinarily attack and destroy invading particles. In people with LAD-1 their neutrophils are dangerously low. That’s why the new data about this treatment is so encouraging.

In a news release, Jonathan Schwartz, M.D., Chief Medical Officer of Rocket, says early results in the CIRM-funded clinical trial, show great promise:

“Patients with severe LAD-I have neutrophil CD18 expression of less than 2% of normal, with extremely high mortality in early childhood. In this first patient, an increase to 47% CD18 expression sustained over six months demonstrates that RP-L201 has the potential to correct the neutrophil deficiency that is the hallmark of LAD-I. We are also pleased with the continued visible improvement of multiple disease-related skin lesions. The second patient has recently been treated, and we look forward to completing the Phase 1 portion of the registrational trial for this program.”

The results were released at the 23rd Annual Meeting of the American Society of Gene and Cell Therapy.

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These microscopic images show gene expression in muscle stem and progenitor cells as they mature from early development to adulthood (left to right). As part of this process, the cells switch from actively expressing one key gene (green) to another (violet); this is accompanied by the growth of muscle fibers (red).
Photo courtesy: Cell Stem Cell/UCLA Broad Stem Cell Research Center

When you are going on a road-trip you need a map to help you find your way. It’s the same with stem cell research. If you are going to develop a new way to treat devastating muscle diseases, you need to have a map to show you how to build new muscle stem cells. And that’s what researchers at the Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at UCLA – with help from CIRM funding – have done.

The team took muscle progenitor cells – which show what’s happening in development before a baby is born – and compared them to muscle stem cells – which control muscle development after a baby is born. That enabled them to identify which genes are active at what stage of development.

In a news release, April Pyle, senior author of the paper, says this could open the door to new therapies for a variety of conditions:

“Muscle loss due to aging or disease is often the result of dysfunctional muscle stem cells. This map identifies the precise gene networks present in muscle progenitor and stem cells across development, which is essential to developing methods to generate these cells in a dish to treat muscle disorders.”

The study is published in the journal Cell Stem Cell.

Can stem cells help people who have had a stroke? Ask the experts.

Stroke is the third leading cause of death and disability in the US. Every 45 seconds someone in the US has a stroke. Every year around 275,000 people die from a stroke many more survive but are often impaired by the brain attack. The impact is not just physical, but psychological and emotional. It takes an enormous toll on individuals and their families. So, it’s not surprising that there is a lot of research underway to try and find treatments to help people, including using stem cells.

That’s why CIRM is hosting a special Facebook Live ‘Ask the Stem Cell Team About Stroke event on Wednesday, March 25th at noon PDT. Just head over to our Facebook Page on the 25th at noon to hear from two great guests.

We will be joined by Dr. Tom Carmichael, a Professor of Neurology and the Co-Director of the UCLA Broad Stem Cell Center. He has a number of CIRM grants focused on helping repair the damage caused by strokes.

CIRM Senior Science Officer, Dr. Lila Collins, will also join us to talk about other stem cell research targeting stroke, its promise and some of the problems that still need to be overcome.

You will have a chance to ask questions of both our experts, either live on the day or by sending us questions in advance at info@cirm.ca.gov.

CIRM supported study finds that a gene associated with autism influences brain stem cells

Dr. Bennett Novitch, UCLA Broad Stem Cell Research Center
Image Credit: UCLA Broad Stem Cell Research Center

In a previous blog post, we discussed new findings in a CIRM supported study at the Salk Institute for Autism Spectrum Disorder (ASD), a developmental disorder that comes in broad ranges and primarily affects communication and behavior.

This week, a new study, also supported by CIRM, finds that a gene associated with ASD, intellectual disability, and language impairment can affect brain stem cells, which in turn, influence early brain development. Dr. Bennett Novitch and his team at UCLA evaluated a gene, called Foxp1, which has been previously studied for its function in the neurons in the developing brain.

Image showing brain cells with lower levels of Foxp1 function (left) and higher levels (right). neural stem cells are stained in green; secondary progenitors and neurons in red.
Image Credit: UCLA Broad Stem Cell Research Center

In this study, Dr. Novitch and his team looked at Foxp1 levels in the brains of developing mouse embryos. What they discovered is that, in normal developing mice the gene was active much earlier than previous studies had indicated. It turns out that the gene was active during the period when neural stem cells are just beginning to expand in numbers and generate a subset of brain cells found deep within the developing brain.

When mice lacked the gene entirely, there were fewer neural stem cells at early stages of brain development, as well as fewer brain cells deep within the developing brain. Alternatively, when the levels of the gene were above normal, the researchers found significantly more neural stem cells and brain cells deep within the developing brain. Additionally, higher levels of the neural stem cells were observed in mice with high levels of the gene even after they were born.

In a press release from UCLA, Dr. Novitch explains how the different levels of the gene can be tied to the variation of Foxp1 levels seen in ASD patients.

“What we saw was that both too much and too little Foxp1 affects the ability of neural stem cells to replicate and form certain neurons in a specific sequence in mice. And this fits with the structural and behavioral abnormalities that have been seen in human patients.”

The full study was published in Cell Reports.