Research Targeting Prostate Cancer Gets Almost $4 Million Support from CIRM

Prostate cancer

A program hoping to supercharge a patient’s own immune system cells to attack and kill a treatment resistant form of prostate cancer was today awarded $3.99 million by the governing Board of the California Institute for Regenerative Medicine (CIRM)

In the U.S., prostate cancer is the second most common cause of cancer deaths in men.  An estimated 170,000 new cases are diagnosed each year and over 29,000 deaths are estimated in 2018.  Early stage prostate cancer is usually managed by surgery, radiation and/or hormone therapy. However, for men diagnosed with castrate-resistant metastatic prostate cancer (CRPC) these treatments often fail to work and the disease eventually proves fatal.

Poseida Therapeutics will be funded by CIRM to develop genetically engineered chimeric antigen receptor T cells (CAR-T) to treat metastatic CRPC. In cancer, there is a breakdown in the natural ability of immune T-cells to survey the body and recognize, bind to and kill cancerous cells. Poseida is engineering T cells and T memory stem cells to express a chimeric antigen receptor that arms these cells to more efficiently target, bind to and destroy the cancer cell. Millions of these cells are then grown in the laboratory and then re-infused into the patient. The CAR-T memory stem cells have the potential to persist long-term and kill residual cancer calls.

“This is a promising approach to an incurable disease where patients have few options,” says Maria T. Millan, M.D., President and CEO of CIRM. “The use of chimeric antigen receptor engineered T cells has led to impressive results in blood malignancies and a natural extension of this promising approach is to tackle currently untreatable solid malignancies, such as castrate resistant metastatic prostate cancer. CIRM is pleased to partner on this program and to add it to its portfolio that involves CAR T memory stem cells.”

Poseida Therapeutics plans to use the funding to complete the late-stage testing needed to apply to the Food and Drug Administration for the go-ahead to start a clinical trial in people.

Quest Awards

The CIRM Board also voted to approve investing $10 million for eight projects under its Discovery Quest Program. The Quest program promotes the discovery of promising new stem cell-based technologies that will be ready to move to the next level, the translational category, within two years, with an ultimate goal of improving patient care.

Among those approved for funding are:

  • Eric Adler at UC San Diego is using genetically modified blood stem cells to treat Danon Disease, a rare and fatal condition that affects the heart
  • Li Gan at the Gladstone Institutes will use induced pluripotent stem cells to develop a therapy for a familial form of dementia
  • Saul Priceman at City of Hope will use CAR-T therapy to develop a treatment for recurrent ovarian cancer

Because the amount of funding for the recommended applications exceeded the money set aside, the Application Subcommittee voted to approve partial funding for two projects, DISC2-11192 and DISC2-11109 and to recommend, at the next full Board meeting in October, that the projects get the remainder of the funds needed to complete their research.

The successful applications are:

 

APPLICATION

 

TITLE

 

INSTITUTION

CIRM COMMITTED FUNDING
DISC2-11131 Genetically Modified Hematopoietic Stem Cells for the

Treatment of Danon Disease

 

 

U.C San Diego

 

$1,393,200

 

DISC2-11157 Preclinical Development of An HSC-Engineered Off-

The-Shelf iNKT Cell Therapy for Cancer

 

 

U.C. Los Angeles

 

$1,404,000

DISC2-11036 Non-viral reprogramming of the endogenous TCRα

locus to direct stem memory T cells against shared

neoantigens in malignant gliomas

 

 

U.C. San Francisco

 

$900,000

DISC2-11175 Therapeutic immune tolerant human islet-like

organoids (HILOs) for Type 1 Diabetes

 

 

Salk Institute

 

$1,637,209

DISC2-11107 Chimeric Antigen Receptor-Engineered Stem/Memory

T Cells for the Treatment of Recurrent Ovarian Cancer

 

 

City of Hope

 

$1,381,104

DISC2-11165 Develop iPSC-derived microglia to treat progranulin-

deficient Frontotemporal Dementia

 

 

Gladstone Institutes

 

$1,553,923

DISC2-11192 Mesenchymal stem cell extracellular vesicles as

therapy for pulmonary fibrosis

 

 

U.C. San Diego

 

$865,282

DISC2-11109 Regenerative Thymic Tissues as Curative Cell

Therapy for Patients with 22q11 Deletion Syndrome

 

 

Stanford University

 

$865,282

 

 

Stem Cell Agency Heads to Inland Empire for Free Patient Advocate Event

UCRiversidePatientAdvocateMtg_EventBrite copy

I am embarrassed to admit that I have never been to the Inland Empire in California, the area that extends from San Bernardino to Riverside counties.  That’s about to change. On Monday, April 16th CIRM is taking a road trip to UC Riverside, and we’re inviting you to join us.

We are holding a special, free, public event at UC Riverside to talk about the work that CIRM does and to highlight the progress being made in stem cell research. We have funded 45 clinical trials in a wide range of conditions from stroke and cancer, leukemia, lymphoma, vision loss, diabetes and sickle cell disease to name just a few. And will talk about how we plan on funding many more clinical trials in the years to come.

We’ll be joined by colleagues from both UC Riverside, and City of Hope, talking about the research they are doing from developing new imaging techniques to see what is happening inside the brain with diseases like Alzheimer’s, to using a patient’s own cells and immune system to attack deadly brain cancers.

It promises to be a fascinating event and of course we want to hear from you, our supporters, friends and patient advocates. We are leaving plenty of time for questions, so we can hear what’s on your mind.

So, join us at UC Riverside on Monday, April 16th from 12.30pm to 2pm. The doors open at 11am so you can enjoy a poster session (highlighting some of the research at UCR) and a light lunch before the event. Parking will be available on site.

Visit the Eventbrite page we have created for all the information you’ll need about the event, including a chance to RSVP and book your place.

The event is free so feel free to share this with anyone and everyone you think might be interested in joining us.

 

 

Gladstone scientists tackle heart failure by repairing the heart from within

Modern medicine often involves the development of a drug or treatment outside the body, which is then given to a patient to fix, improve or even prevent their condition. But what if you could regenerate or heal the body using the cells and tissue already inside a patient?

Scientists at the Gladstone Institutes are pursuing such a strategy for heart disease. In a CIRM-funded study published today in the journal Cell, the team identified four genes that can stimulate adult heart muscle cells, called cardiomyocytes, to divide and proliferate within the hearts of living mice. This discovery could be further developed as a strategy to repair cardiac tissue damage caused by heart disease and heart attacks.

Regenerating the Heart

Heart disease is the leading cause of death in the US and affects over 24 million people around the world. When patients experience a heart attack, blood flow is restricted to the heart, and parts of the heart muscle are damaged or die due to the lack of oxygen. The heart is unable to regenerate new healthy heart muscle, and instead, cardiac fibroblasts generate fibrous scar tissue to heal the injury. This scar tissue impairs the heart’s ability to pump blood, causing it to work harder and putting patients at risk for future heart failure.

Deepak Srivastava, President of the Gladstone Institutes and a senior investigator there, has dedicated his life’s research to finding new ways to regenerate heart tissue. Previously, his team developed methods to reprogram mouse and human cardiac fibroblasts into beating cardiomyocytes in hopes of one day restoring heart function in patients. The team is advancing this research with the help of a CIRM Discovery Stage research grant, which will aid them in developing a gene therapy product that delivers reprogramming factors into scar tissue cells to regenerate new heart muscle.

In this new study, Srivastava took a slightly different approach and attempted to coax cardiomyocytes, rather than cardiac fibroblasts, to divide and regenerate the heart. During development, fetal cardiomyocytes rapidly divide to create heart tissue. This regenerative ability is lost in adult cardiomyocytes, which are unable to divide because they’ve already exited the cell cycle (a series of phases that a cell goes through that ultimately results in its division).

Deepak Srivastava (left) and first author Tamer Mohamed (right). Photo credits: Diana Rothery.

Unlocking proliferative potential

Srivastava had a hunch that genes specifically involved in the cell division could be used to jump-start an adult cardiomyocyte’s re-entry into the cell cycle. After some research, they identified four genes (referred to as 4F) involved in controlling cell division. When these genes were turned on in adult cardiomyocytes, the cells started to divide and create new heart tissue.

This 4F strategy worked in mouse and rat cardiomyocytes and also was successful in stimulating cell division in 15%-20% of human cardiomyocytes. When they injected 4F into the hearts of mice that had suffered heart attacks, they observed an improvement in their heart function after three months and a reduction in the size of the scar tissue compared to mice that did not receive the injection.

The team was able to further refine their method by replacing two of the four genes with chemical inhibitors that had similar functions. Throughout the process, the team did not observe the development of heart tumors caused by the 4F treatment. They attributed this fact to the short-term expression of 4F in the cardiomyocytes. However, Srivastava expressed caution towards using this method in a Gladstone news release:

“In human organs, the delivery of genes would have to be controlled carefully, since excessive or unwanted cell division could cause tumors.”

First stop heart, next stop …

This study suggests that it’s possible to regenerate our tissues and organs from within by triggering adult cells to re-enter the cell cycle. While more research is needed to ensure this method is safe and worthy of clinical development, it could lead to a regenerative treatment strategy for heart failure.

Srivastava will continue to unravel the secrets to the proliferative potential of cardiomyocytes but predicts that other labs will pursue similar methods to test the regenerative potential of adult cells in other tissues and organs.

“Heart cells were particularly challenging because when they exit the cell cycle after birth, their state is really locked down—which might explain why we don’t get heart tumors. Now that we know our method is successful with this difficult cell type, we think it could be used to unlock other cells’ potential to divide, including nerve cells, pancreatic cells, hair cells in the ear, and retinal cells.”


Related Links:

Creating a platform to help transplanted stem cells survive after a heart attack

heart

Developing new tools to repair damaged hearts

Repairing, even reversing, the damage caused by a heart attack is the Holy Grail of stem cell researchers. For years the Grail seemed out of reach because the cells that researchers transplanted into heart attack patients didn’t stick around long enough to do much good. Now researchers at Stanford may have found a way around that problem.

In a heart attack, a blockage cuts off the oxygen supply to muscle cells. Like any part of our body starved off oxygen the muscle cells start to die, and as they do the body responds by creating a layer of scars, effectively walling off the dead tissue from the surviving healthy tissue.  But that scar tissue makes it harder for the heart to effectively and efficiently pump blood around the body. That reduced blood flow has a big impact on a person’s ability to return to a normal life.

In the past, efforts to transplant stem cells into the heart had limited success. Researchers tried pairing the cells with factors called peptides to help boost their odds of surviving. That worked a little better but most of the peptides were also short-lived and weren’t able to make a big difference in the ability of transplanted cells to stick around long enough to help the heart heal.

Slow and steady approach

Now, in a CIRM-funded study published in the journal Nature Biomedical Engineering, a team at Stanford – led by Dr. Joseph Wu – believe they have managed to create a new way of delivering these cells, one that combines them with a slow-release delivery mechanism to increase their chances of success.

The team began by working with a subset of bone marrow cells that had been shown in previous studies to have what are called “pro-survival factors.” Then, working in mice, they identified three peptides that lived longer than other peptides. That was step one.

Step two involved creating a matrix, a kind of supporting scaffold, that would enable the researchers to link the three peptides and combine them with a delivery system they hoped would produce a slow release of pro-survival factors.

Step three was seeing if it worked. Using fluorescent markers, they were able to show, in laboratory tests, that unlinked peptides were rapidly released over two or three days. However, the linked peptides had a much slower release, lasting more than 15 days.

Out of the lab and into animals

While these petri dish experiments looked promising the big question was could this approach work in an animal model and, ultimately, in people. So, the team focused on cardiac progenitor cells (CPCs) which have shown potential to help repair damaged hearts, but which also have a low survival rate when transplanted into hearts that have experienced a heart attack.

The team delivered CPCs to the hearts of mice and found the cells without the pro-survival matrix didn’t last long – 80 percent of the cells were gone four days after they were injected, 90 percent were gone by day ten. In contrast the cells on the peptide-infused matrix were found in large numbers up to eight weeks after injection. And the cells didn’t just survive, they also engrafted and activated the heart’s own survival pathways.

Impact on heart

The team then tested to see if the treatment was helping improve heart function. They did echocardiograms and magnetic resonance imaging up to 8 weeks after the transplant surgery and found that the mice treated with the matrix combination had a statistically improved left ventricular function compared to the other mice.

Jayakumar Rajadas, one of the authors on the paper told CIRM that, because the matrix was partly made out of collagen, a substance the FDA has already approved for use in people, this could help in applying for approval to test it in people in the future:

“This paper is the first comprehensive report to demonstrate an FDA-compliant biomaterial to improve stem cell engraftment in the ischemic heart. Importantly, the biomaterial is collagen-based and can be readily tested in humans once regulatory approval is obtained.”

 

Comparing two cellular reprogramming methods from one donor’s cells yields good news for iPSCs

In 2012, a mere six years after his discovery of induced pluripotent stem cells (iPSCs), Shinya Yamanaka was awarded the Nobel Prize in Medicine. Many Nobel winners aren’t recognized until decades after their initial groundbreaking studies. That goes to show you the importance of Yamanaka’s technique, which can reprogram a person’s cells, for example skin or blood, into embryonic stem cell-like iPSCs by just adding a small set of reprogramming factors.

These iPSCs are pluripotent, meaning they can be specialized, or differentiated, into virtually any cell type in the body. With these cells in hand, researchers have a powerful tool to study human disease and to develop treatments using human cells directly from patients. And at the same time, this cell source helps avoid the ethical concerns related to embryonic stem cells.

iPSC_Wu

Induced pluripotent stem cell (iPSC) colonies.
Image Credit: Joseph Wu

Still, there has been lingering uneasiness about how well iPSCs match up to embryonic stem cells (ESCs), considered the gold-standard of pluripotent stem cells. One source of those concerns is that the iPSC method doesn’t completely reprogram cells and they retain memory of their original cell source, in the form of chemical – also called epigenetic – modifications of the cells’ DNA structure. So, if a researcher were to make, say, heart muscle cells from iPSCs that have an epigenetic memory of its skin cell origins, any resulting conclusions about a given disease study or cell therapy could be less accurate than ESC-related results. But a report published yesterday in PNAS should help relieve these worries.

The CIRM-funded study – a collaboration between the labs of Joseph Wu and Michael Synder at Stanford University and Shoukhrat Mitalipov at Oregon Health & Science University – carried out an exhaustive series of experiments that carefully compared the gene activity and cell functions of iPSC-derived cells with cells derived from embryonic stem cells. The teams sought to compare cells generated from the same person to be sure any differences were not the result of genetics. To make this “apples-to-apples” comparison, they generated embryonic stem cells using another reprogramming technique called somatic cell nuclear transfer (SCNT).

With SCNT, a nucleus from an adult cell is transferred to an egg which has its own nucleus removed. The resulting cell becomes reprogrammed back into an embryo from which embryonic stem cells are generated – the researchers call them NT-ESCs for short. In this study, the skin cell sample used for making the iPSCs and the cell nucleus used for making the NT-ESCs came from the same person. In scientific lingo, the iPSCs and SCNT stem cells are considered isogenic.

Now, it turns out the NT-ESC reprogramming process is more complete and eliminates epigenetic memory of the original cell source. So why even bother with iPSCs if you have NT-ESCs? There are big disadvantages with SCNT: it’s a complex technique – only a limited number of labs pull it off – and it requires donated human eggs which carries ethical issues. So, if a direct comparison iPSCs and SNCT stem cells shows little difference then it would be fair to argue that iPSCs can replace NT-ESCs for deriving patient-specific stem cells.

And that’s exactly what the teams found, as Dr. Wu summarized it to me in an interview:

“Direct comparison between differentiated cells derived from iPSCs and SCNT had never been performed because it had been difficult to generate patient-specific ESCs by the SCNT method. Collaborating with Dr. Shoukhrat Mitalipov at Oregon Health & Science University and Dr. Michael Snyder at Stanford University, we compared patient-specific cardiomocytes (heart muscle cells) and endothelial (blood vessel) cells derived by these two reprogramming methods (SCNT and iPSCs) and found they were relatively equivalent regarding molecular and functional features.”

PSC-ECs2 copy

Blood vessel cells derived by iPSC (left) and SCNT (right) reprogramming methods.
Image credit: Joseph Wu

Because the heart muscle and blood vessel cells were similar regardless of reprogramming method, it suggests that the epigenetic memory that remained in the iPSCs is less of a worry. Dr. Wu explained to me this way:

joewu

Joseph Wu

“If iPSCs carry substantial epigenetic memory of the cell-of-origin, it is unlikely these iPSCs can differentiate to a functional cardiac cell or blood vessel cell. Only the stem cells free of significant epigenetic memory can differentiate into functional cells.”

 

Hopefully these results hold up over time because it will bode well for the countless iPSC-related disease studies as well as the growing number of iPSC-related projects that are nearing clinical trials.

CIRM-Funded Clinical Trials Targeting the Heart, Pancreas, and Kidneys

This blog is part of our Month of CIRM series, which features our Agency’s progress towards achieving our mission to accelerate stem cell treatments to patients with unmet medical needs.

This week, we’re highlighting CIRM-funded clinical trials to address the growing interest in our rapidly expanding clinical portfolio. Today we are featuring trials in our organ systems portfolio, specifically focusing on diseases of the heart/vasculature system, the pancreas and the kidneys.

CIRM has funded a total of nine trials targeting these disease areas, and eight of these trials are currently active. Check out the infographic below for a list of our currently active trials.

For more details about all CIRM-funded clinical trials, visit our clinical trials page and read our clinical trials brochure which provides brief overviews of each trial.

Attractive new regenerative medicine tool uses magnets to shape and stimulate stem cells

The ultimate goal of tissue engineers who work in the regenerative medicine field is to replace damaged or diseased organs with new ones built from stem cells. To accomplish the feat, these researchers are developing new tools and techniques to manipulate and specialize stem cells into three dimensional structures. Some popular methods – which we’ve blogged about often – include the use of bioscaffolds as well as 3D bioprinting . This week, a research team at the Laboratoire Matière et Systèmes Complexes in France has developed an attractive (pun intended!) new tool that uses magnetized stem cells to both manipulate and stimulate the cells into 3D shapes.

The magnetic stretcher: this all-in-one system can both form and mechanically stimulate an aggregate of magnetized embryonic stem cells. Image: © Claire Wilhelm / Laboratoire Matière et systèmes complexes (CNRS/Université Paris Diderot).

The study, reported on Monday in Nature Communications, used embryonic stem cells which were incubated with magnetic nanoparticles. The cells readily take up the nanoparticles which allowed the scientists to group the individual cells using magnets. But first the team needed to show that the nanoparticles had no negative effects on the cells. Comparing the iron nanoparticle-laden stem cells to iron-free cells showed no difference in the cells’ survival and their ability to divide.

It was also important to make sure the introduction of nanoparticles had no impact on the stem cell’s pluripotency; that is, its ability to maintain its unspecialized state. A visual check of the cells through a microscope showed that they grew together in rounded clumps, a hallmark of undifferentiated, pluripotent cells. In addition, the key genes that bestow pluripotency onto embryonic stem cells were still active after the addition of the nanoparticles.

The stem cells’ ability to mature into various cell types, like heart muscle or nerve, is key to any successful tissue engineering project. So, the next important assessment of these magnetized cells was to make sure their ability to differentiate, or specialize, was still intact. The typical first step to differentiating embryonic stem cells is to form so-called embryoid bodies (EBs), which are 3D groups of pluripotent stem cells which begin differentiating into the three fundamental tissues types: mesoderm (gives rise to muscle, bone, fat), ectoderm (gives rise to nerve, hair, eyes), endoderm (gives rise to intestines, liver). Using a popular technique, called the hanging drop method, the team showed that the presence of the nanoparticles did not negatively affect embryoid body formation.

In fact, the use of magnets to form embryoid bodies provided several advantages over the hanging drop method. The hanging drop technique requires multiple, time-consuming steps and the resulting embryoid bodies tend to be inconsistent in size and shape. Use of the magnets, on the other hand, instantaneously assembled the stem cells into consistently round aggregates. And by precisely adjusting the magnetic force used, the scientists could also vary the size of the embyroid body, which is an important variable to control since the embryoid size can impact its ability to differentiate.

While the magnet used to form the embryoid bodies was kept stable, the researchers included another magnet which they could move. With this setup, the team was able to stretch and shape the group of cells without the need of scaffolds or the need to physically contact the cells. Several previous studies, using flat, 2-dimensional petri dishes, have shown that the stiffness and flexibility of the dish can stimulate gene activity by affecting cell shape. In this study, the researchers found that when the magnet was moved in a cyclical pattern that imitates the rhythm of a heart beat, the embryoid bodies were, if you can believe it, nudged toward a heart muscle fate. A press release by France’s National Center of Scientific Research (CNRS), which funded the study, explained the big picture implications of this new technique:

“This “all-in-one” approach, which makes it possible to build and manipulate tissue within the same system, could thus prove to be a powerful tool both for biophysical studies and tissue engineering.”

Hearts and brains are center stage at CIRM Patient Advocate event

Describing the work of a government agency is not the most exciting of topics. Books on the subject would probably be found in the “Self-help for Insomniacs” section of a good bookstore (there are still some around). But at CIRM we are fortunate. When we talk about what we do, we don’t talk about the mechanics of our work, we talk about our mission: accelerating stem cell therapies to people with unmet medical needs.

Yesterday at the Gladstone Institutes in San Francisco we did just that, talking about the progress being made in stem cell research to an audience of friends, supporters and patient advocates. We had a lot to talk about, including the 35 clinical trials we have funded so far, and our goals and hopes for the future.

We were lucky to have Dr. Deepak Srivastava and Dr. Steve Finkbeiner from Gladstone join us to talk about their work. Some people are good scientists, some are good communicators. Deepak and Steve are great scientists and equally great communicators.

Deepak Srivastava highlighted ongoing stem cell research at the Gladstone
(Photo: Todd Dubnicoff/CIRM)

Deepak is the Director of the Roddenberry Stem Cell Center at Gladstone (and yes, it’s named after Gene Roddenberry of Star Trek fame) and an expert on heart disease. He talked about how advances in research have enabled us to turn heart scar tissue cells into new heart muscle cells, creating the potential to use a person’s own cells to help them recover from a heart attack.

“If you have a heart attack, your heart turns that muscle into scar tissue which affects the heart’s ability to pump blood around the body. We identified a combination of factors that support cells that are already in your heart and we have found a way of converting those scar cells into muscle. This could help repair the heart enough so you may not need a transplant, but you can lead a much more normal life.”

He said this research is now advancing to the point where they hope it could be ready for testing in people in the not too distant future and joked that his father, who has had a heart attack, volunteered to be the second person to try it. “Not the first but definitely the second.”

Steve, who is the Director of the Taube/Koret Center for Neurodegenerative Disease Research, specializes in problems in the brain; everything from Alzheimer’s and Parkinson’s to schizophrenia and ALS (also known as Lou Gehrig’s disease.

He talked about his uncle, who has end stage Parkinson’s disease, and how he sees first-hand how devastating this neurodegenerative disease is, and how that personal connection helps motivate him to work ever harder.

He talked about how so many therapies that look promising in mice fail when they are tested in people:

“A huge motivation for me has been to try and figure out a more reliable way to test these potential therapies and to move discoveries from the lab and into clinical trials in patients.”

Steve is using ordinary skin cells or tissue samples, taken from people with Parkinson’s and Alzheimer’s and other neurological conditions, and using the iPSC technique developed by Shinya Yamanaka (who is a researcher at Gladstone and also Director of CIRA in Japan) turns them into the kinds of cells found in the brain. These cells then enable him to study how these different diseases affect the brain, and come up with ways that might stop their progress.

Steve Finkbeiner is using human stem cells to model brain diseases
(Photo: Todd Dubnicoff/CIRM)

He uses a robotic microscope – developed at Gladstone – that allows his team to study these cells and test different potential therapies 24 hours a day, seven days a week. This round-the-clock approach will hopefully help speed up his ability to find something that help patients.

The CIRM speakers – Dr. Maria Millan, our interim President and CEO – and Sen. Art Torres (ret.) the Vice Chair of our Board and a patient advocate for colorectal cancer – talked about the progress we are making in helping push stem cell research forward.

Dr. Millan focused on our clinical trial work and how our goal is to create a pipeline of promising projects from the work being done by researchers like Deepak and Steve, and move those out of the lab and into clinical trials in people as quickly as possible.

Sen. Art Torres (Ret.)
(Photo: Todd Dubnicoff/CIRM)

Sen. Torres focused on the role of the patient advocate at CIRM and how they help shape and influence everything we do, from the Board’s deciding what projects to support and fund, to our creating Clinical Advisory Panels which involve a patient advocate helping guide clinical trial teams.

The event is one of a series that we hold around the state every year, reporting back to our friends and supporters on the progress being made. We feel, as a state agency, that we owe it to the people of California to let them know how their money is being spent.

We are holding two more of these events in the near future, one at UC Davis in Sacramento on October 10th, and one at Cedars-Sinai Medical Center in Los Angeles on October 30th.

Stem cell stories that caught our eye: bubble baby therapy a go in UK, in-utero stem cell trial and novel heart disease target

There were lots of CIRM mentions in the news this week. Here are two brief recaps written by Karen Ring to get you up to speed. A third story by Todd Dubnicoff summarizes an promising finding related to heart disease by researchers in Singapore.  

CIRM-funded “bubble baby” disease therapy gets special designation by UK.
Orchard Therapeutics, a company based in the UK and the US, is developing a stem cell-based gene therapy called OTL-101 to treat a primary immune disease called adenosine-deaminase deficient severe combined immunodeficiency (ADA-SCID), also known as “bubble baby disease”. CIRM is funding a Phase 1/2 clinical trial led by Don Kohn of UCLA in collaboration with Orchard and the University College in London.

In July, the US Food and Drug Administration (FDA) awarded OTL-101 Rare Pediatric Disease Designation (read more about it here), which makes the therapy eligible for priority review by the FDA, and could give it a faster route to being made more widely available to children in need.

On Tuesday, Orchard announced further good news that OTL-101 received “Promising Innovative Medicine Designation” by the UK’s Medicines and Healthcare Products Regulatory Agency (MHRA). In a news release, the company explained how this designation bodes well for advancing OTL-101 from clinical trials into patients,

“The designation as Promising Innovative Medicine is the first step of a two-step process under which OTL-101 can benefit from the Early Access to Medicine Scheme (“EAMS”). Nicolas Koebel, Senior Vice President for Business Operations at Orchard, added: “With this PIM designation we can potentially make OTL-101 available to UK patients sooner under the Early Access to Medicine Scheme”.

CIRM funded UCSF clinical trial mentioned in SF Business Times
Ron Leuty, reporter at the San Francisco Business Times, published an article about a CIRM-funded trial out of UCSF that is targeting a rare genetic blood disease called alpha thalassemia major, describing it as, “The world’s first in-utero blood stem cell transplant, soon to be performed at the University of California, San Francisco, could point the way toward pre-birth cures for a range of blood diseases, such as sickle cell disease.”

Alpha Thalassemia affects the ability of red blood cells to carry oxygen because of a reduction in a protein called hemoglobin. The UCSF trial, spearheaded by UCSF Pediatric surgeon Dr. Tippi MacKenzie, is hoping to use stem cells from the mother to treat babies in the womb to give them a better chance at surviving after birth.

In an interview with Leuty, Tippi explained,

“Our goal is to put in enough cells so the baby won’t need another transplant. But even if we fall short, if we can just establish 1 percent maternal cells circulating in the child, it will establish tolerance and then they can get the booster transplant.”

She also emphasized the key role that CIRM funded played in the development and launch of this clinical trial.

“CIRM is about more than funding for studies, MacKenzie said. Agency staff has provided advice about how to translate animal studies into work in humans, she said, as well as hiring an FDA consultant, writing an investigational new drug application and setting up a clinical protocol.”

“I’m a clinician, but running a clinical trial is different,” MacKenzie said. “CIRM’s been incredibly helpful in helping me navigate that.”

Heart, heal thyself: the story of Singheart
When you cut your finger or scrape a knee, a scab forms, allowing the skin underneath to regenerate and repair itself. The heart is not so lucky – it has very limited self-healing abilities. Instead, heart muscle cells damaged after a heart attack form scar tissue, making each heart beat less efficient. This condition can lead to chronic heart disease, the number one killer of both men and women in the US.

A mouse heart cell with 2 nuclei (blue) and Singheart RNA labelled by red fluorescent dyes.
Credit: A*STAR’s Genome Institute of Singapore

Research has shown that newborn mice retain the ability to completely regenerate and repair injuries to the heart because their heart muscle cells, or cardiomyocytes, are still able to divide and replenish damaged cells. But by adulthood, the mouse cardiomyocytes lose the ability to stimulate the necessary cell division processes. A research team in Singapore wondered what was preventing cardiomyocytes cell division in adult mice and if there was some way to lift that block.

This week in Nature Communications, they describe the identification of a molecule they call Singheart that may be the answer to their questions. Using tools that allow the analysis of gene activity in single cells revealed that a rare population of diseased cardiomyocytes are able to crank up genes related to cell division. And further analysis showed Singheart, a specialized genetic molecule called a long non-coding RNA, played a role in blocking this cell division gene.

As lead author Dr. Roger Foo, a principal investigator at Genome Institute of Singapore (GIS) and the National University Health System (NUHS), explained in a press release, these findings may lead to new self-healing strategies for heart disease,

“There has always been a suspicion that the heart holds the key to its own healing, regenerative and repair capability. But that ability seems to become blocked as soon as the heart is past its developmental stage. Our findings point to this potential block that when lifted, may allow the heart to heal itself.”

Treatments, cures and clinical trials: an in-person update on CIRM’s progress

Patients and Patient Advocates are at the heart of everything we do at CIRM. That’s why we are holding three free public events in the next few months focused on updating you on the stem cell research we are funding, and our plans for the future.

Right now we have 33 projects that we have funded in clinical trials. Those range from heart disease and stroke, to cancer, diabetes, ALS (Lou Gehrig’s disease), two different forms of vision loss, spinal cord injury and HIV/AIDS. We have also helped cure dozens of children battling deadly immune disorders. But as far as we are concerned we are only just getting started.

Over the course of the next few years, we have a goal of adding dozens more clinical trials to that list, and creating a pipeline of promising therapies for a wide range of diseases and disorders.

That’s why we are holding these free public events – something we try and do every year. We want to let you know what we are doing, what we are funding, how that research is progressing, and to get your thoughts on how we can improve, what else we can do to help meet the needs of the Patient Advocate community. Your voice is important in helping shape everything we do.

The first event is at the Gladstone Institutes in San Francisco on Wednesday, September 6th from noon till 1pm. The doors open at 11am for registration and a light lunch.

Gladstone Institutes

Here’s a link to an Eventbrite page that has all the information about the event, including how you can RSVP to let us know you are coming.

We are fortunate to be joined by two great scientists, and speakers – as well as being CIRM grantees-  from the Gladstone Institutes, Dr. Deepak Srivastava and Dr. Steve Finkbeiner.

Dr. Srivastava is working on regenerating heart muscle after it has been damaged. This research could not only help people recover from a heart attack, but the same principles might also enable us to regenerate other organs damaged by disease. Dr. Finkbeiner is a pioneer in diseases of the brain and has done ground breaking work in both Alzheimer’s and Huntington’s disease.

We have two other free public events coming up in October. The first is at UC Davis in Sacramento on October 10th (noon till 1pm) and the second at Cedars-Sinai in Los Angeles on October 30th (noon till 1pm). We will have more details on these events in the coming weeks.

We look forward to seeing you at one of these events and please feel free to share this information with anyone you think might be interested in attending.