Saying farewell to an old friend

There are some people who, when you think of them, always bring a smile to your face. Dr. Bert Lubin was one of those people. Sadly, we lost Bert to brain cancer two days ago. But the impact he had, not just as an advocate for stem cell research but as a pioneer in sickle cell disease research and a champion for children’s health, will live on.

Bert had a number of official titles but probably the one he was most proud of was President & CEO of Children’s Hospital Oakland (now UCSF Benioff Children’s Hospital Oakland). But it wasn’t the title that he cared about, it was the opportunity it gave him to make a difference in the life of children in Oakland, to create a program to find new treatments and cures for a life-threatening disease. And he has made a difference.

As I started to write this tribute to Bert, I thought about who I should ask for a quote. And then I realized I had the perfect person. Bert himself. I was fortunate enough to interview him in December 2018, when he decided to step down after eight years on the CIRM Board.  As always, he had his own positive spin on that, saying: “I don’t see myself leaving. I’m just repurposing what is my role in CIRM. I’m recycling and reinventing.”

And Bert was always full of invention.

He grew up in Bellevue, a small town outside Pittsburgh, PA. His parents ran a fruit and vegetable market there and, growing up, Bert often worked in the store. It wasn’t something he enjoyed but he said he learned some valuable lessons.

“I think what happened in my childhood is that I learned how to sell. I am a salesman. I hated working in that store, I hated it, but I liked the communication with people, they trusted me, I could sell things and they were good things. Like Christmas. I’m Jewish, we were the only Jews in that community, and at Christmas we sold Christmas trees, but the trees were sometimes crooked and they were $2.99 a tree so I convinced families that I could go to their house and set the tree so it looked straight and I helped them decorate it and they loved it.”

He said, thinking back on his life it’s almost as if there were a plan, even if he wasn’t aware of it.

“I started thinking about that more recently, I started wondering how did this even happen? I’m not a religious person but it’s almost like there’s some fate. How did I get there? It’s not that I planned it that way and it’s certainly not that my parents planned it because I was the first in my family to go to high school let alone college. My parents, when I went to medical school and then decided I wanted to spend more time in an academic direction, they were upset. They wanted me to go into practice in a community that I grew up in and be economically secure and not be on the fringe in what an academic life is like.”

And then, fate stepped in and brought him to the San Francisco Bay Area.

“What happened was, I was at the University of Pennsylvania having trained at Boston Children’s and Philadelphia Children’s, where I had started a sickle cell disease program, and was asked to look at a job in southern California to start a sickle cell program there. So, I flew to San Francisco because a lot of people I’d studied with were now working at UCSF and I thought it would be fun to see them before going down to southern California. They took me out to dinner and showed me around and I said this place is beautiful, I can play tennis out here all year round, there’s lots of music – I love jazz – and they said ‘you know Bert, have you looked at Oakland Children’s hospital? We want to start a sickle cell program center, but the patients are all in Oakland and the patient population that would be served is in Oakland. But if you came out to the Bay Area we could partner with you to start that program. 

“So, when I walked in the door here (at Oakland) and said ‘I want to create this northern California sickle cell center with UC’ the staff that was here said ‘you know we’re not a research hospital, we are a community based hospital’. I said, ‘I’m not saying you shouldn’t be that but I’m trying to create an opportunity here’ and they said to me ‘as long as you don’t ask for any money you can go and do whatever you want’.

‘They recognized that I had this fire in me to really create something that was novel. And the warmth and community commitment from this place is something that attracted me and then allowed me to build on that.

“For example, when I became the director of the research program we had $500,000 in NIH grants and when I left we had $60 million. We just grew. Why did we grow? Because we cared about the faculty and the community. We had a lovely facility, which was actually the home of the Black Panther party. It was the Black Panthers who started screening for sickle cell on street corners here in Oakland, and they were the start of the national sickle cell act so there’s a history here and I like that history.

“Then I got a sense of the opportunities that stem cell therapies would have for a variety of things, certainly including sickle cell disease, and I thought if there’s a chance to be on the CIRM Board, as an advocate for that sickle cell community, I think I’d be a good spokesperson. So, I applied. I just thought this was an exciting opportunity.

“I thought it was a natural fit for me to add some value, I only want to be on something where I think I add value.”

Bert added value to everything he did. And everyone he met felt valued by him. He was a mentor to so many people, young physicians and nurses, students starting out on their careers. And he was a friend to those in need.

He was an extraordinary man and we are grateful that we were able to call him a colleague, and a friend, for as long as we did.

When Burt stepped down from Children’s his colleagues put together this video about his life and times. It seems appropriate to share it again and remind ourselves of the gift that he was to everyone fortunate enough to know him.

CIRM Board Approves Clinical Trials Targeting COVID-19 and Sickle Cell Disease

Coronavirus particles, illustration.

Today the governing Board of the California Institute for Regenerative Medicine (CIRM) approved new clinical trials for COVID-19 and sickle cell disease (SCD) and two earlier stage projects to develop therapies for COVID-19.

Dr. Michael Mathay, of the University of California at San Francisco, was awarded $750,000 for a clinical trial testing the use of Mesenchymal Stromal Cells for respiratory failure from Acute Respiratory Distress Syndrome (ARDS). In ARDS, patients’ lungs fill up with fluid and are unable to supply their body with adequate amounts of oxygen. It is a life-threatening condition and a major cause of acute respiratory failure. This will be a double-blind, randomized, placebo-controlled trial with an emphasis on treating patients from under-served communities.

This award will allow Dr. Matthay to expand his current Phase 2 trial to additional underserved communities through the UC Davis site.

“Dr. Matthay indicated in his public comments that 12 patients with COVID-related ARDS have already been enrolled in San Francisco and this funding will allow him to enroll more patients suffering from COVID- associated severe lung injury,” says Dr. Maria T. Millan, CIRM’s President & CEO. “CIRM, in addition to the NIH and the Department of Defense, has supported Dr. Matthay’s work in ARDS and this additional funding will allow him to enroll more COVID-19 patients into this Phase 2 blinded randomized controlled trial and expand the trial to 120 patients.”

The Board also approved two early stage research projects targeting COVID-19.

  • Dr. Stuart Lipton at Scripps Research Institute was awarded $150,000 to develop a drug that is both anti-viral and protects the brain against coronavirus-related damage.
  • Justin Ichida at the University of Southern California was also awarded $150,00 to determine if a drug called a kinase inhibitor can protect stem cells in the lungs, which are selectively infected and killed by the novel coronavirus.

“COVID-19 attacks so many parts of the body, including the lungs and the brain, that it is important for us to develop approaches that help protect and repair these vital organs,” says Dr. Millan. “These teams are extremely experienced and highly renowned, and we are hopeful the work they do will provide answers that will help patients battling the virus.”

The Board also awarded Dr. Pierre Caudrelier from ExcellThera $2 million to conduct a clinical trial to treat sickle cell disease patients

SCD is an inherited blood disorder caused by a single gene mutation that results in the production of “sickle” shaped red blood cells. It affects an estimated 100,000 people, mostly African American, in the US and can lead to multiple organ damage as well as reduced quality of life and life expectancy.  Although blood stem cell transplantation can cure SCD fewer than 20% of patients have access to this option due to issues with donor matching and availability.

Dr. Caudrelier is using umbilical cord stem cells from healthy donors, which could help solve the issue of matching and availability. In order to generate enough blood stem cells for transplantation, Dr. Caudrelier will be using a small molecule to expand these blood stem cells. These cells would then be transplanted into twelve children and young adults with SCD and the treatment would be monitored for safety and to see if it is helping the patients.

“CIRM is committed to finding a cure for sickle cell disease, the most common inherited blood disorder in the U.S. that results in unpredictable pain crisis, end organ damage, shortened life expectancy and financial hardship for our often-underserved black community” says Dr. Millan. “That’s why we have committed tens of millions of dollars to fund scientifically sound, innovative approaches to treat sickle cell disease. We are pleased to be able to support this cell therapy program in addition to the gene therapy approaches we are supporting in partnership with the National Heart, Lung and Blood Institute of the NIH.”

Scientists at Gladstone and UCSF form two new research institutes

Dr. Melanie Ott (left) and Dr. Alexander Marson (right)
Image Credit: Gladstone Institutes

In a previous blog post, we talked about how scientists at the Gladstone Institutes have shifted their current operations towards helping with the current coronavirus pandemic. Now scientists at Gladstone and U.C. San Francisco have formed two new research institutes to broaden its impact on unsolved diseases such as COVID-19.

One of these institutes is the Gladstone Institute of Virology and will be lead by Dr. Melanie Ott. The immediate focus of this newly formed institution will be the current coronavirus pandemic. Additionally, it will focus on searching for new therapies against future infectious diseases. The Gladstone Institute of Virology will focus on how viruses interact with human cells to cause disease and how to intervene in that process. Dr. Ott’s goal is to identify pathways these viruses use to infect human cells as a way to develop innovative treatments.

In a press release from Gladstone Institutes, Dr. Ott talks about the goal of her work in more detail.

“Contrary to the current strategy of combining several drugs to treat one virus, we want to develop one drug against multiple viruses. As antibiotic resistance becomes an increasingly urgent problem, we will also delve into how we can use viruses as therapeutics, which involves using viruses against themselves or to fight bacteria.”

The second institute is a collaboration between UCSF and Gladstone Institutes and is called the Gladstone-UCSF Institute of Genomic Immunology. It will be lead by Dr. Alexander Marson and will combine the study of genomics and immunology to develop new therapies. One of the primary goals will be to understand the role that genetics play in human immune cells. By manipulating these cells, the immune system could potentially be altered to treat cancer, infectious diseases, autoimmune diseases, and even neurological conditions such as Alzheimer’s.

In the same press release from Gladstone Institutes, Dr. Marson discusses the importance these collaborations hold for pushing scientific innovation.

“These rapidly advancing fields are starting to converge in ways that are too big for any single lab to take on. The impetus to start a new institute was the realization that we need to create an ecosystem to bring together people with different perspectives to think about transformative opportunities for how patients can be treated in the future.”

Stem Cells for Parkinson’s Disease

While the world has been turned upside down by the coronavirus pandemic, the virus poses an increased threat to people with Parkinson’s disease (PD). Having a compromised immune system, particularly involving the lungs, means people with PD are at higher risk of some of the more dangerous complications of COVID-19. So, this seems like an appropriate time for CIRM to hold a special Facebook Live “Ask the Stem Cell Team” About Parkinson’s disease.

We are holding the event on Tuesday, May 5th at noon PDT.

The initial reason for the Facebook Live was the CIRM Board approving almost $8 million for Dr. Krystof Bankiewicz at Brain Neurotherapy Bio, Inc. to run a Phase 1 clinical trial targeting PD. Dr. Bankiewicz is using a gene therapy approach to promote the production of a protein called GDNF, which is best known for its ability to protect dopaminergic neurons, the kind of cell damaged by Parkinson’s. The approach seeks to increase dopamine production in the brain, alleviating PD symptoms and potentially slowing down the disease progress.

Dr. Bankiewicz will be joined by two of CIRM’s fine Science Officers, Dr. Lila Collins and Dr. Kent Fitzgerald. They’ll talk about the research targeting Parkinson’s that CIRM is funding plus other promising research taking place.

And we are delighted to have a late addition to the team. Our CIRM Board member and patient advocate for Parkinson’s disease, Dr. David Higgins. David has a long history of advocacy for PD and adds the invaluable perspective of someone living with PD.

As always, we want this to be as interactive as possible, so we want to get your questions. You can do this on the day, posting them alongside the live feed, or you can send them to us ahead of time at info@cirm.ca.gov. We’ll do our best to answer as many as we can on the day, and those we don’t get to during the broadcast we’ll answer in a later blog.

We look forward to seeing you there.

How developing a treatment for a rare disease could lead to therapies for other, not-so-rare conditions

Logan Lacy, a child with AADC Deficiency: Photo courtesy Chambersburg Public Opinion

Tomorrow, the last day in February, is Rare Disease Day. It’s a day dedicated to raising awareness about rare diseases and the impact they have on patients and their families.

But the truth is rare diseases are not so rare. There are around 7,000 diseases that affect fewer than 200,000 Americans at any given time. In fact, it’s estimated that around one in 20 people will live with a rare disease at some point in their lives. Many may die from it.

This blog is about one man’s work to find a cure for one of those rare diseases, and how that could lead to a therapy for something that affects many millions of people around the world.

Dr. Krystof Bankiewicz; Photo courtesy Ohio State Medical Center

Dr. Krystof Bankiewicz is a brain surgeon at U.C. San Francisco and The Ohio State University. He is also the President and CEO at Brain Neurotherapy Bio and a world expert in delivering gene and other therapies to the brain. More than 20 years ago, he began trying to develop a treatment for Parkinson’s disease by looking at a gene responsible for AADC enzyme production, which plays an important role in the brain and central nervous system.  AADC is critical for the formation of serotonin and dopamine, chemicals that transmit signals between nerve cells, the latter of which plays a role in the development of Parkinson’s disease.

While studying the AADC enzyme, Dr. Bankiewicz learned of an extremely rare disorder where children lack the AADC enzyme that is critical for their development.  This condition significantly inhibits communication between the brain and the rest of the body, leading to extremely limited mobility, muscle spasms, and problems with overall bodily functions.  As a result of this, AADC deficient children require lifelong care, and particularly severe cases can lead to death in the first ten years of life.

“These children can’t speak. They have no muscle control, so they can’t do fundamental things such as walking, supporting their neck or lifting their arms,” says Dr. Bankiewicz. “They have involuntary movements, experience tremendously painful spasms almost like epileptic seizures. They can’t feed themselves and have to be fed through a tube in their stomach.”

So, Dr. Bankiewicz, building on his understanding of the gene that encodes AADC, developed an experimental approach to deliver a normal copy, injected directly into the midbrain, the area responsible for dopamine production. The DDC gene was inserted into a virus that acted as a kind of transport, carrying the gene into neurons, the brain cells affected by the condition. It was hoped that once inside, the gene would allow the body to produce the AADC enzyme and, in turn, enable it to produce its own dopamine .

And that’s exactly what happened.

“It’s unbelievable. In the first treated patients their motor system is dramatically improved, they are able to better control their movements, they can eat, they can sleep well. These are tremendous benefits. We have been following these children for almost three years post-treatment, and the progression we see doesn’t stop, it keeps going and we see these children keep on improving. Now they are able to get physical therapy to help them. Some are even able to go to school.”

For Dr. Bankiewicz this has been decades in the making, but that only makes it all the more gratifying: “This doesn’t happen very often in your lifetime, to be able to use all your professional experience and education to help people and see the impact it has on people’s lives.”

So far he has treated 20 patients from the US, UK and all over the world.

But he is far from finished.

Already the therapy has been given Orphan Drug Designation and Regenerative Medicine Advanced Therapy designation by the US Food and Drug Administration. The former is a kind of financial incentive to companies to develop drugs for rare diseases. The latter gives therapies that are proving to be both safe and effective, an accelerated path to approval for wider use. Dr. Bankiewicz hopes that will help them raise the funds needed to treat children with this rare condition.  “We want to make this affordable for families. We are not in this to make a profit; we want to get foundations and maybe even pharmaceutical companies to help us treat the kids, so they don’t have to cover the full costs themselves.”

CIRM has not funded any of this work, but the data and results from this research were important factors in our Board awarding Dr. Bankiewicz more than $5.5 million to begin a clinical trial for Parkinson’s disease. Dr. Bankiewicz is using a similar approach in that work to the one he has shown can help children with AADC deficiency.

While AADC deficiency may only affect a few hundred children worldwide, it’s estimated that Parkinson’s affects more than ten million people; one million of those in the US alone.  Developing this gene therapy technique in a rare disease, therefore, may ultimately benefit large populations of patients.

So, on this Rare Disease Day, we celebrate Dr. Bankiewicz and others whose compassion and commitment to finding treatments to help those battling rare conditions are helping change the world, one patient at a time.

You can follow the story of one child treated by Dr. Bankiewicz here.

The Top CIRM Blogs of 2019

This year the most widely read blog was actually one we wrote back in 2018. It’s the transcript of a Facebook Live: “Ask the Stem Cell Team” event about strokes and stroke recovery. Because stroke is the third leading cause of death and disability in the US it’s probably no surprise this blog has lasting power. So many people are hoping that stem cells will help them recover from a stroke.

But of the blogs that we wrote and posted this year there’s a really interesting mix of topics.

The most read 2019 blog was about a potential breakthrough in the search for a treatment for type 1 diabetes (T1D).  Two researchers at UC San Francisco, Dr. Matthias Hebrok and Dr. Gopika Nair developed a new method of replacing the insulin-producing cells in the pancreas that are destroyed by type 1 diabetes. 

Dr. Matthias Hebrok
Dr. Gopika Nair

Dr. Hebrok described it as a big advance saying: “We can now generate insulin-producing cells that look and act a lot like the pancreatic beta cells you and I have in our bodies. This is a critical step towards our goal of creating cells that could be transplanted into patients with diabetes.”

It’s not too surprising a blog about type 1 diabetes was at the top. This condition affects around 1.25 million Americans, a huge audience for any potential breakthrough. However, the blog that was the second most read is the exact opposite. It is about a rare disease called cystinosis. How rare? Well, there are only around 500 children and young adults in the US, and just 2,000 worldwide diagnosed with this condition.  

It might be rare but its impact is devastating. A genetic mutation means children with this condition lack the ability to clear an amino acid – cysteine – from their body. The buildup of cysteine leads to damage to the kidneys, eyes, liver, muscles, pancreas and brain.

Dr. Stephanie Cherqui

UC San Diego researcher Dr. Stephanie Cherqui and her team are taking the patient’s own blood stem cells and, in the lab, genetically re-engineering them to correct the mutation, then returning the cells to the patient. It’s hoped this will create a new, healthy blood system free of the disease.

Dr. Cherqui says if it works, this could help not just people with cystinosis but a wide array of other disorders: “We were thrilled that the stem cells and gene therapy worked so well to prevent tissue degeneration in the mouse model of cystinosis. This discovery opened new perspectives in regenerative medicine and in the application to other genetic disorders. Our findings may deliver a completely new paradigm for the treatment of a wide assortment of diseases including kidney and other genetic disorders.”

Sickled cells

The third most read blog was about another rare disease, but one that has been getting a lot of media attention this past year. Sickle cell disease affects around 100,000 Americans, mostly African Americans. In November the Food and Drug Administration (FDA) approved Oxbryta, a new therapy that reduces the likelihood of blood cells becoming sickle shaped and clumping together – causing blockages in blood vessels.

But our blog focused on a stem cell approach that aims to cure the disease altogether. In many ways the researchers in this story are using a very similar approach to the one Dr. Cherqui is using for cystinosis. Genetically correcting the mutation that causes the problem, creating a new, healthy blood system free of the sickle shaped blood cells.

Two other blogs deserve honorable mentions here as well. The first is the story of James O’Brien who lost the sight in his right eye when he was 18 years old and now, 25 years later, has had it restored thanks to stem cells.

The fifth most popular blog of the year was another one about type 1 diabetes. This piece focused on the news that the CIRM Board had awarded more than $11 million to Dr. Peter Stock at UC San Francisco for a clinical trial for T1D. His approach is transplanting donor pancreatic islets and parathyroid glands into patients, hoping this will restore the person’s ability to create their own insulin and control the disease.

2019 was certainly a busy year for CIRM. We are hoping that 2020 will prove equally busy and give us many new advances to write about. You will find them all here, on The Stem Cellar.

The Most Important Gift of All

Photo courtesy American Hospital Association

There are many players who have a key role in helping make a stem cell therapy work. The scientists who develop the therapy, the medical team who deliver it and funders like CIRM who provide the money to make this all happen. But vital as they are, in some therapies there is another, even more important group; the people who donate life-saving organs and tissues for transplant and research.

Organ and tissue donation saves lives, increases knowledge of diseases, and allow for the development of novel medications to treat them. When individuals or their families authorize donation for transplant or medical research, they allow their loved ones to build a long-lasting legacy of hope that could not be accomplished in any other way.

Four of CIRM’s clinical trials involve organ donations – three kidney transplant programs (you can read about those here, here and here) and one targeting type 1 diabetes.

Dr. Nikole Neidlinger, the Chief Medical Officer with Donor Network West – the federally designated organ and tissue recovery organization for Northern California and Nevada – says it is important to recognize the critical contribution made in a time of grief and crisis by the families of deceased donors. 

“For many families who donate, a loved one has died, and they are in shock. Even so, they are willing to say yes to giving others a second chance at life and to help others to advance science. Without them, none of this would be possible. It’s the ultimate act of generosity and compassion.”

The latest CIRM-funded clinical trial involving donated tissue is with Dr. Peter Stock and his team at UCSF. They are working on a treatment for type 1 diabetes (T1D), where the body’s immune system destroys its own pancreatic beta cells. These cells are necessary to produce insulin, which regulates blood sugar levels in the body.

In the past people have tried transplanting beta cells, from donated pancreatic islets, into patients with type 1 diabetes to try and reverse the course of the disease. However, this requires islets from multiple donors and the shortage of organ and tissue donors makes this difficult to do.

Dr. Stock’s clinical trial at UCSF aims to address these limitations.  He is going to transplant both pancreatic islets and parathyroid glands, from the same donor, into T1 patients. It’s hoped this combination approach will increase beta cell survival, potentially boosting long-term insulin production and removing the need for multiple donors.  And because the transplant is placed in the patient’s forearm, it makes it easier to monitor the effectiveness and accessibility of the islet transplants. Of equal importance, the development of this site will facilitate the transplantation of stem cell derived beta cells, which are very close to clinical application.

“As a transplant surgeon, it is an absolute privilege to be able to witness the life-saving organ transplants made possible by the selfless generosity of the donor families. It is hard to imagine how families have the will to think about helping others at a time of their greatest grief. It is this willingness to help others that restores my faith in humanity”

Donor Network West plays a vital role in this process. In 2018 alone, the organization recovered 702 donor samples for research. Thanks to the generosity of the donors/donor families, the donor network has been able to provide parathyroid and pancreas tissue essential to make this clinical trial a success”

“One organ donor can save the lives of up to eight people and a tissue donor can heal more than 75 others,” says Dr. Neidlinger. “For families, the knowledge that they are transforming someone’s life, and possibly preventing another family from experiencing this same loss, can serve as a silver lining during their time of sorrow. .”

Organs that can be donated

Kidney (x2), Heart, Lungs (x2), Liver, Pancreas, Intestine

Tissue that can be donated

Corneas, Heart valves, Skin, Bone, Tendons, Cartilage, Veins

Currently, there are over 113,000 people in the U.S. waiting for an organ transplant, of which 84 % are in need of kidneys.  Sadly, 22 people die every day waiting for an organ transplant that does not come in time. The prospect of an effective treatment for type 1 diabetes means hope for thousands of people living with the chronic condition.

Rare Disease, Type 1 Diabetes, and Heart Function: Breakthroughs for Three CIRM-Funded Studies

This past week, there has been a lot of mention of CIRM funded studies that really highlight the importance of the work we support and the different disease areas we make an impact on. This includes important research related to rare disease, Type 1 Diabetes (T1D), and heart function. Below is a summary of the promising CIRM-funded studies released this past week for each one of these areas.

Rare Disease

Comparison of normal (left) and Pelizaeus-Merzbacher disease (PMD) brains (right) at age 2. 

Pelizaeus-Merzbacher disease (PMD) is a rare genetic condition affecting boys. It can be fatal before 10 years of age and symptoms of the disease include weakness and breathing difficulties. PMD is caused by a disruption in the formation of myelin, a type of insulation around nerve fibers that allows electrical signals in the brain to travel quickly. Without proper signaling, the brain has difficulty communicating with the rest of the body. Despite knowing what causes PMD, it has been difficult to understand why there is a disruption of myelin formation in the first place.

However, in a CIRM-funded study, Dr. David Rowitch, alongside a team of researchers at UCSF, Stanford, and the University of Cambridge, has been developing potential stem cell therapies to reverse or prevent myelin loss in PMD patients.

Two new studies, of which Dr. Rowitch is the primary author, published in Cell Stem Cell, and Stem Cell Reports, respectively report promising progress in using stem cells derived from patients to identify novel PMD drugs and in efforts to treat the disease by directly transplanting neural stem cells into patients’ brains. 

In a UCSF press release, Dr. Rowitch talks about the implications of his findings, stating that,

“Together these studies advance the field of stem cell medicine by showing how a drug therapy could benefit myelination and also that neural stem cell transplantation directly into the brains of boys with PMD is safe.”

Type 1 Diabetes

Viacyte, a company that is developing a treatment for Type 1 Diabetes (T1D), announced in a press release that the company presented preliminary data from a CIRM-funded clinical trial that shows promising results. T1D is an autoimmune disease in which the body’s own immune system destroys the cells in the pancreas that make insulin, a hormone that enables our bodies to break down sugar in the blood. CIRM has been funding ViaCyte from it’s very earliest days, investing more than $72 million into the company.

The study uses pancreatic precursor cells, which are derived from stem cells, and implants them into patients in an encapsulation device. The preliminary data showed that the implanted cells, when effectively engrafted, are capable of producing circulating C-peptide, a biomarker for insulin, in patients with T1D. Optimization of the procedure needs to be explored further.

“This is encouraging news,” said Dr. Maria Millan, President and CEO of CIRM. “We are very aware of the major biologic and technical challenges of an implantable cell therapy for Type 1 Diabetes, so this early biologic signal in patients is an important step for the Viacyte program.”

Heart Function

Although various genome studies have uncovered over 500 genetic variants linked to heart function, such as irregular heart rhythms and heart rate, it has been unclear exactly how they influence heart function.

In a CIRM-funded study, Dr. Kelly Frazer and her team at UCSD studied this link further by deriving heart cells from induced pluripotent stem cells. These stem cells were in turn derived from skin samples of seven family members. After conducting extensive genome-wide analysis, the team discovered that many of these genetic variations influence heart function because they affect the binding of a protein called NKX2-5.

In a press release by UCSD, Dr. Frazer elaborated on the important role this protein plays by stating that,

“NKX2-5 binds to many different places in the genome near heart genes, so it makes sense that variation in the factor itself or the DNA to which it binds would affect that function. As a result, we are finding that multiple heart-related traits can share a common mechanism — in this case, differential binding of NKX2-5 due to DNA variants.”

The full results of this study were published in Nature Genetics.

Moving a great idea targeting diabetes out of the lab and into a company

Tejal Desai in her lab at UCSF: Photo courtesy Todd Dubnicoff

It’s always gratifying to see research you have helped support go from being an intriguing idea to something with promise to a product that is now the focus of a company. It’s all the more gratifying if the product in question might one day help millions of people battling diabetes.

That’s the case with a small pouch being developed by a company called Encellin. The pouch is the brainchild of Tejal Desai, Ph.D., a professor of bioengineering at UCSF and a CIRM grantee.

Encellin’s encapsulation device

“It’s a cell encapsulation device, so this material can essentially protect beta cells from the immune system while allowing them to function by secreting insulin. We are placing stem cell-derived beta cells into the pouch which is then implanted under the skin. The cells are then able to respond to changes in sugar or glucose levels in the blood by pumping out insulin.  By placing the device in a place that is accessible we can easily remove it if we have to, but also we can recharge it and put in new cells as well.”

While the pouch was developed in Dr. Desai’s lab, the idea to take it from a promising item and try to turn it into a real-world therapy came from one of Dr. Desai’s former students, Crystal Nyitray, Ph.D.

Crystal Nyitray: Photo courtesy FierceBiotech

After getting her PhD, Nyitray went to work for the pharmaceutical giant Sanofi. In an article in FierceBiotech she says that’s where she realized that the pouch she had been working on at UCSF had real potential.

“During that time, I started to realize we really had something, that everything that pharma or biotech was looking at was something we had been developing from the ground up with those specific questions in mind,”

So Dr. Nyitray went to work for QB3, the institute created by UC San Francisco to help startups develop their ideas and get funding. The experience she gained there gave her the confidence to be the co-founder and CEO of Encellin.

Dr. Desai is a scientific advisor to Encellin. She says trying to create a device that contains insulin-secreting cells is not new. Many previous attempts failed because once the device was placed in the body, the immune system responded by creating fibrosis or scarring around it which blocked the ability of the cells to get out.

But she thinks their approach has an advantage over previous attempts.

“This is not a new idea, the idea has been around for 40 or more years but getting it to work is hard. We have a convergence of getting the right cell types and combining that with our knowledge of immunology and then the material science where we can design materials at this scale to get the kind of function that we need.

Dr. Nyitray ““If we can reduce fibrosis, it really helps the cells get nutrients better, survive better and signal more effectively. It’s really critical to their success.”

Dr. Desai says the device is still in the early stages of being tested, but already it’s showing promise.

“We have done testing in animals. Where the company is taking this is now to see if we can take this to larger animals and then ultimately people.”

She says without CIRM’s support none of this would have happened.

“CIRM has been really instrumental in helping us refine the cell technology piece of it, to get really robust cells and also to support the development to push the materials, to understand the biology, to really understand what was happening with the cell material interface. We know we have a lot of challenges ahead, but we are really excited to see if this could work.”

We are excited too. We are looking forward to seeing what Encellin does in the coming years. It could change the lives of millions of people around the world.

No pressure. 

Getting the inside scoop on the stem cell agency

There’s a wonderful moment at the end of the movie The Candidate (starring Robert Redford, 87% approval on Rotten Tomatoes!) about a modern political campaign for a US Senate seat. Redford (spoiler alert) plays a come-from-behind candidate and at the end when he wins he turns to his campaign manager and says “Now what?”.

I think that’s how a lot of people associated with Proposition 71 felt when it was approved by California voters in 2004, creating CIRM. Now what? During the campaign you are so focused on crossing the finish line that when the campaign is over you have to pause because you just realized it wasn’t the finishing line, it was actually the starting line.

For us “now what” involved hiring a staff, creating oversight groups of scientists and ethics experts, developing strategies and then mechanisms for funding, and then mechanisms for tracking that funding to make sure it was being used properly. It was creating something from scratch and trying to do something that no state agency had done before.

Fifteen years later we are coming to the end of the funding provided by Prop 71 and that question keeps popping up again, “Now what?” And that’s what we are going to be talking about in our next Facebook Live.

We have three great experts on our panel. They are scientists and researchers and leaders in biotech, but also members of our CIRM Board. We rely on their experience and expertise in making key decisions and you can rely on them to pull back the curtain and talk about the things that matter most to them in helping advance our mission, and in helping secure our legacy.

Anne-Marie Duliege MD, has more than 25 years of experience in the medical world, starting out as a pediatrician and then moving into research. She has experience developing new therapies for auto-immune disorders, lung problems and infectious diseases.

Like Anne-Marie, Joe Panetta, has years of experience working in the research field, and is currently President & CEO of Biocom, the California association that advocates for more than 1,200 companies, universities and research institutes working in biotechnology.

Finally, Dave Martin MD, came to CIRM after stints at the National Institutes of Health (NIH), UC San Francisco, Genentech, Chiron and several other highly-regarded organizations. He is also the co-founder, chairman and CEO of AvidBiotics, a privately held biotechnology company in South San Francisco.

Each brings a different perspective to the work that we do at CIRM, and each enriches it not just with their intelligence and experience, but also with their compassion for the patients and commitment to our mission.

So, join us on Thursday, July 25th from noon till 1pm (PDT) for a special Facebook Live “Ask the Stem Cell Team” to understand how we got where we are, how the rest of the field is doing, and what happens next. It promises to be a fascinating hour.