We were saddened to learn today of the death of Susan Solomon, the CEO and co-founder of the New York Stem Cell Foundation (NYSCF), a non-profit organization that supports stem cell research around the world. As CEO, Ms. Solomon raised over $400M for stem cell research, helping to catalyze the field and transform the future of medical research.
The foundation announced the news on its website, saying she died after a long battle with ovarian cancer.
CIRM’s Chair Jonathan Thomas said she will be greatly missed. “We were so terribly sorry to hear about Susan’s passing. She was a titan in our field who did immeasurable good for patients everywhere. We have so valued our relationship with her and NYSCF through the years.”
Like many patient advocates Ms. Solomon became active when a family member was hit by disease. In her case, it was in 1992 when her ten year old son Ben was diagnosed with type 1 diabetes. A lawyer by training and a longtime business executive she put her skills to work to identify the best way to help her son, and others with type 1 diabetes. In an interview in the Wall Street Journal she says that background really helped: “As a lawyer, you learn how to learn about a new field instantly,” and, she added, “I’m really comfortable asking dumb questions.”
After much research and many conversations with scientists she concluded that stem cells were the most promising way to help patients. In 2005 she co-founded NYSCF.
Dr. Jeanne Loring, the Director of the Center for Regenerative Medicine at the Scripps Research Institute, says Ms. Solomon’s death is a huge blow to the field: “I have worked with NYSCF for the last 5 years, on the project to study neuroinflammation in space using iPSC-derived neurons. Susan was one in a billion, she threw all of her considerable energy into starting and sustaining the only stand-alone research institute that I know of in the US dedicated to stem cell research.”
It’s not often you get excited talking about company mergers, but a deal announced today is something worth getting excited about, particularly if you have type 1 diabetes (T1D).
Today Vertex announced it was buying ViaCyte for $320 million in cash. Why is that important? Because both companies are working on developing stem cell therapies for people with type 1 diabetes, so combining the two may help speed up that work.
Now, in the interests of full disclosure the California Institute for Regenerative Medicine (CIRM) has been supporting ViaCyte’s work for some years now, investing in nine different research programs, including two clinical trials with the company.
ViaCyte has been developing an implantable device which contains pancreatic endoderm cells that mature over a few months and turn into insulin-producing pancreatic islet cells, the kind destroyed by T1D.
Vertex is taking a slightly different approach, manufacturing synthetic islet cells which are then injected into the patient.
In a news release both companies said the deal – which is slated to be completed later this year – would help speed up that work.:
“VX-880 has successfully demonstrated clinical proof of concept in T1D, and the acquisition of ViaCyte will accelerate our goal of transforming, if not curing T1D by expanding our capabilities and bringing additional tools, technologies and assets to our current stem cell-based programs,” said Reshma Kewalramani, M.D., Chief Executive Officer and President of Vertex.
“ViaCyte’s commitment to finding a functional cure for T1D is shared by Vertex, and this acquisition will allow Vertex to deploy ViaCyte’s tools, technologies and assets toward the development of Vertex’s multiple cell replacement therapy approaches designed to reduce the burden of millions of people living with T1D worldwide,” said Michael Yang, President and Chief Executive Officer of ViaCyte.
Dr. Maria Millan, CIRM’s President and CEO, says it’s always gratifying to see a project we have supported continue to progress.
“We are delighted at the news that Vertex and ViaCyte are combining their experience, expertise and resources in working to develop a stem cell therapy for type 1 diabetes. At CIRM we pride ourselves on helping de-risk projects, giving promising research the support it needs to attract outside investment. We have been big supporters of ViaCyte’s work over many years. That support has been vital in helping lead to this deal. We believe this is good news for both companies and hope it will ultimately be even better news for everyone with type 1 diabetes.”
Taylor Lookofsky (center), a person with IPEX syndrome, with his father Brian and Dr. Rosa Bacchetta
IPEX syndrome is a rare condition where the body can’t control or restrain an immune response, so the person’s immune cells attack their own healthy tissue. The syndrome mostly affects boys, is diagnosed in the first year of life and is often fatal. Today the governing Board of the California Institute for Regenerative Medicine (CIRM) invested almost $12 million in a therapy being tested in a clinical trial to help these patients.
Children born with IPEX syndrome have abnormalities in the FOXP3 gene. This gene controls the production of a type of immune cell called a T Regulatory or Treg cell. Without a normal FOXP3 +Treg cells other immune cells attack the body leading to the development of IPEX syndrome, Type 1 diabetes, severe eczema, damage to the small intestines and kidneys and failure to thrive.
Current treatments involve the use of steroids to suppress the immune system – which helps ease symptoms but doesn’t slow down the progression of the disease – or a bone marrow stem cell transplant. However, a transplant requires a healthy, closely matched donor to reduce the risk of a potentially fatal transplant complication called graft vs host disease, in which the donated immune cells attack the recipient’s tissues.
Dr. Rosa Bacchetta and her team at Stanford University have developed a therapy using the patient’s own natural CD4 T cells that, in the lab, have been genetically modified to express the FoxP3 gene and converted into Treg cells. Those cells are then re-infused into the patient with a goal of determining if this approach is both safe and beneficial. Because the cells come from the patients there will be fewer concerns about the need for immunosuppressive treatment to stop the body rejecting the cells. It will also help avoid the problems of finding a healthy donor and graft vs host disease.
Dr. Bacchetta has received approval from the Food and Drug Administration (FDA) to test this approach in a Phase 1 clinical trial for patients suffering with IPEX syndrome.
“Children with IPEX syndrome clearly represent a group of patients with an unmet medical need, and this therapy could make a huge difference in their lives,” says Dr. Maria T. Millan, the President and CEO of CIRM. “Success of this treatment in this rare disease presents far-reaching potential to develop treatments for a larger number of patients with a broad array of immune disorders resulting from dysfunctional regulatory T cells.”
In addition to a strong scientific recommendation to fund the project the review team also praised it for the applicants’ commitment to the principles of Diversity, Equity and Inclusion in their proposal. The project proposes a wide catchment area, with a strong focus on enrolling people who are low-income, uninsured or members of traditionally overlooked racial and ethnic minority communities.
One of the huge advantages of a stem cell agency like CIRM (not that there is anything out there quite like us, but anyway) is our ability to support projects as they progress from a great idea to a therapy actually being tested in people.
Exhibit A on that front came via a news release from ViaCyte, a company that is developing a new approach to helping people with severe Type 1 Diabetes (T1D).
Unlike type 2 diabetes, which is largely diet & lifestyle related and develops over time, T1D is an autoimmune condition where the person’s immune system attacks and destroys the insulin-producing cells in the pancreas. Without those cells and insulin the body is not able to regulate blood sugar levels and that can lead to damage to the heart, kidneys, eyes and nerves. In severe cases it can be fatal.
ViaCyte (which has been supported with more than $72 million from CIRM) has developed a pouch that can be implanted under the skin in the back. This pouch contains stem cells that over a period of a few months turn into insulin-producing pancreatic islet cells, the kind destroyed by T1D. The goal is for these cells to monitor blood flow and when they detect blood sugar or glucose levels are high, can secrete insulin to restore them to a safe level.
They tested this approach in 15 patients in a Phase 1 clinical trial in Canada. Their findings, published in the journals Cell Stem Celland Cell Reports Medicine, show that six months after implantation, the cells had turned into insulin-producing islet cells. They also showed a rise in C-peptide levels after patients ate a meal. C-peptides are a sign your body is producing insulin so the rise in that number was a good indication the implanted cells were boosting insulin production.
As Dr. James Shapiro, the Chair of Canada Research and one of the lead authors of the study says, that’s no small achievement: “The data from these papers represent a significant scientific advance. It is the first reported evidence that differentiated stem cells implanted in patients can generate meal-regulated insulin secretion, offering real hope for the incredible potential of this treatment.”
And that wasn’t all. The researchers say that patients spent 13 percent more time in the target range for blood sugar levels than before the treatment, and some were even able to reduce the amount of insulin they injected.
Now this is only a Phase 1 clinical trial so the goal was to test the safety of the pouch, called PEC-Direct (VC-02), to see if the body would tolerate it being implanted and to see if it is effective. The beauty of this method is that the device is implanted under the skin so it can be removed easily if any problems emerge. So far none have.
Ultimately the hope is that this approach will help patients with T1D better regulate their blood sugar levels, improve their health outcomes, and one day even achieve independence from the burden of daily insulin injections.
As someone with a family history of type 1 diabetes (T1D) I know how devastating the condition can be. I also know how challenging it can be to keep it under control and the consequences of failing to do that. Not maintaining healthy blood sugar levels can have a serious impact on the heart, kidney, eyes, nerves, and blood vessels. It can even be fatal.
Right now, controlling T1D means being careful about what you eat, when you eat and how much you eat. It also means regularly checking your blood throughout the day to see if the glucose level is too high or too low. If it’s too high you need to inject insulin; if it’s too low you need to take a fast-acting carbohydrate such as fruit juice or glucose to try and restore it to a healthy level.
That’s why two new approaches to T1D that CIRM has supported are so exciting. They both use small devices implanted under the skin that contain stem cells. The cells can both monitor blood sugar and, if it’s too high, secrete insulin to bring it down.
We sat down with two key members of the Encellin and ViaCyte teams, Dr. Crystal Nyitray and Dr. Manasi Jaiman, to talk about their research, how it works, and what it could mean for people with T1D. That’s in the latest episode of our podcast ‘Talking ‘Bout (re)Generation’.
I think you are going to enjoy it.
This is the size of the implant that ViaCyte is using.This is the size of the implant Encellin is using
Dr. Crystal Nyitray, CEO & Co-founder Encellin
Dr. Manasi Jaiman, Vice President, Clinical Development ViaCyte
As someone who is not always as diligent as he would like to be about sending birthday cards on time, I’m used to sending belated greetings to people. So, I have no shame in sending belated greetings to four CIRM grantees who were inducted into the National Academy of Medicine in 2020.
I say four, but it’s really three and a half. I’ll explain that later.
Being elected to the National Academy of Medicine is, in the NAM’s own modest opinion, “considered one of the highest honors in the fields of health and medicine and recognizes individuals who have demonstrated outstanding professional achievement and commitment to service.”
To be fair, NAM is right. The people elected are among the best and brightest in their field and membership is by election from the other members of NAM, so they are not going to allow any old schmuck into the Academy (which could explain why I am still waiting for my membership).
The CIRM grantees elected last year are:
Dr. Antoni Ribas: Photo courtesy UCLA
Antoni Ribas, MD, PhD, professor of medicine, surgery, and molecular and medical pharmacology, U. C. Los Angeles.
Dr. Ribas is a pioneer in cancer immunology and has devoted his career to developing new treatments for malignant melanoma. When Dr. Ribas first started malignant melanoma was an almost always fatal skin cancer. Today it is one that can be cured.
In a news release Dr. Ribas said it was a privilege to be honored by the Academy: “It speaks to the impact immunotherapy has played in cancer research. When I started treating cases of melanoma that had metastasized to other organs, maybe 1 in 20 responded to treatment. Nobody in their right mind wanted to be a specialist in this field. It was the worst of the worst cancers.”
Dr. Goldberg was honored for his contribution to the understanding of vision loss and ways to reverse it. His lab has developed artificial retinas that transmit images down the optic nerve to the brain through tiny silicon chips implanted in the eye. He has also helped use imaging technology to better improve our ability to detect damage in photoreceptor cells (these are cells in the retina that are responsible for converting light into signals that are sent to the brain and that give us our color vision and night vision)
In a news release he expressed his gratitude saying: “I look forward to serving the goals of the National Academies, and to continuing my collaborative research efforts with my colleagues at the Byers Eye Institute at Stanford and around the world as we further our efforts to combat needless blindness.”
Dr. Anderson was honored for being a leader in the study of autoimmune diseases such as type 1 diabetes. This focus extends into the lab, where his research examines the genetic control of autoimmune diseases to better understand the mechanisms by which immune tolerance is broken.
Understanding what is happening with the immune system, figuring out why it essentially turns on the body, could one day lead to treatments that can stop that, or even reverse it by boosting immune activity.
Dr. John Dick: Photo courtesy University Health Network, Toronto
Remember at the beginning I said that three and a half CIRM grantees were elected to the Academy, well, Canadian researcher, Dr. John Dick is the half. Why? Well, because the award we funded actually went to UC San Diego’s Dennis Carson but it was part of a Collaborative Funding Partnership Program with Dr. Dick at the University of Toronto. So, we are going to claim him as one of our own.
And he’s a pretty impressive individual to partner with. Dr. Dick is best known for developing a test that led to the discovery of leukemia stem cells. These are cells that can evade surgery, chemotherapy and radiation and which can lead to patients relapsing after treatment. His work helped shape our understanding of cancer and revealed a new strategy for curing it.
The cell encapsulation device (right) that is being developed by Encellin, a San Francisco–based biotechnology company. Photo courtesy of Encellin
Type 1 diabetes (t1d) affects every aspect of a person’s life, from what they eat and when they eat, to when they exercise and how they feel physically and emotionally. Because the peak age for being diagnosed with t1d is around 13 or 14 years of age it often hits at a time when a child is already trying to cope with big physical and emotional changes. Add in t1d and you have a difficult time made a lot more challenging.
There are ways to control the disease. Regular blood sugar monitoring and insulin injections can help people manage their condition but those come with their own challenges. Now researchers are taking a variety of different approaches to developing new, innovative ways of helping people with t1d.
One of those companies is Encellin. They are developing a pouch-like device that can be loaded with stem cells and then implanted in the body. The pouch acts like a mini factory, releasing therapies when they are needed.
This work began at UC San Francisco in the lab of Dr. Tejal Desai – with help from CIRM funding – that led to the creation of Encellin. We recently sat down – virtually of course – with Dr. Grace Wei, the co-founder of the company to chat about their work, and their hopes for the future.
Dr. Grace Wei
She said the decision to target t1d was an easy one:
“Type 1 diabetes is an area of great need. It’s very difficult to manage at any age but particularly in children. It affects what they can eat, what they can do, it’s a big burden on the family and can become challenging to manage when people get older.
“It’s an autoimmune disease so everyone’s disease progression is a bit different. People think it’s just a matter of you having too much blood sugar and not enough insulin, but the problem with medicines like insulin is that they are not dynamic, they don’t respond to the needs of your body as they occur. That means people can over-regulate and give themselves too much insulin for what their body needs and if it happens at night, it can be deadly.
Dr. Wei says stem cell research opens up the possibility of developing dynamic therapies, living medicines that are delivered to you by cells that respond to your dynamic needs. That’s where their pouch, called a cell encapsulation device (CED) comes in.
The pouch is tiny, only about the size of a quarter, and it can be placed just under the skin. Encellin is filling the pouch with glucose-sensitive, insulin producing islet cells, the kind of cells destroyed by t1d. The idea is that the cells can monitor blood flow and, when blood sugar is low, secrete insulin to restore it to a healthy level.
Another advantage of the pouch is that it may eliminate the need for the patient to take immunosuppressive medications.
“The pouch is really a means to protect both the patient receiving the cells and the cells themselves. Your body tends to not like foreign objects shoved into it and the pouch in one respect protects the cells you are trying to put into the person. But you also want to be able to protect the person, and that means knowing where the cells are and having a means to remove them if you need to. That’s why it’s good to have a pouch that you can put in the body, take it out if you need, and replace if needed.”
Dr. Wei says it’s a little like making tea with a tea bag. When the need arises the pouch can secrete insulin but it does so in a carefully controlled manner.
“These are living cells and they are responsive, it’s not medicine where you can overdose, these cells are by nature self-regulating.”
They have already tested their approach with a variety of different kinds of islets, in a variety of different kinds of model.
“We’ve tested for insulin production, glucose stimulation and insulin response. We have tested them in a number of animal models and those studies are supporting our submission for a first-in-human safety clinical trial.”
Dr. Wei says if this approach works it could be used for other metabolic conditions such as parathyroid disorders. And she says a lot of this might not be possible without the early funding and support from CIRM.
“CIRM had the foresight to invest in groups that are looking ahead and said it would be great to have renewable cells to transplant into the body (that function properly. We are grateful that groundwork that has been laid and are looking forward to advancing this work.”
And we are looking forward to working with them to help advance that work too.
A diabetic child is checking her blood sugar level (self glycaemia).
Type 1 diabetes affects millions of people. It is a disease where beta islet cells in the pancreas are targeted by the body’s own immune system, destroying the ability to produce insulin. Without insulin, the body cannot break down sugars from the bloodstream that produce energy for organs and that can lead to many significant health problems including damage to the eyes, nerves, and kidneys. It is a life-long condition, most commonly triggered in children and teenagers. However, type 1 diabetes can manifest at any time. I have a family member who developed type 1 diabetes well into adulthood and had to dramatically alter his lifestyle to live with it.
Fortunately most people can now live with the disease. There was a time, dating back to ancient civilizations when getting type 1 diabetes meant early death. Thankfully, over the past hundred years, treatments have been developed to address the disease. The first widespread treatment developed in the 1920s was injections of animal insulin isolated from pancreatic islets in cattle and pigs. Over 50 years later the first genetically engineered human insulin was produced using E. coli bacteria, and variations of this are still used today. However, the disease is still very challenging to manage. My family member constantly monitors his blood sugar and gives himself injections of insulin to regulate his blood sugar.
A therapy that can self-regulate blood sugar levels for diabetes would greatly improve the lives of millions of people that deal with the disease. Pancreatic islet cells transplanted into patients can act as a natural rheostat to continually control blood sugar levels. Pancreas organ transplantation and islet cell transplantation are treatment options that will accomplish this. Both options are limited in supply and patients must be kept on life-long immunosuppression so the body does not reject the transplant. Pancreatic beta cells are also being developed from pluripotent stem cells (these are cells that have the ability to be turned into almost any other kind of cell in the body).
Now in an advance using pluripotent stem cells, Dr. Ronald Evans and his team at the Salk Institute have created cell clusters called organoids that mimic several properties of the pancreas. Previously, in work supported by CIRM, the team discovered that a genetic switch called ERR-gamma caused the cells to both produce insulin and be functional to respond to sugar levels in the bloodstream. They incorporated these findings to create their functional islet clusters that they term “human islet-like islet organoids” (HILOs). Knowing that the immune system is a major barrier for long term cell replacement therapy, Dr. Evans’ team engineered the HILOs, in work also funded by CIRM, to be resistant to immune cells by expressing the checkpoint protein PD-L1. PD-L1 is a major target for immunotherapies whose discovery led to a Nobel Prize in 2018. Expressing PD-L1 acts as an immune blocker.
When the PD-L1 engineered HILOs were transplanted into diabetic mice with functioning immune systems, they were able to sustain blood glucose control for time periods up to 50 days. The researchers also saw significantly less mobilization of immune cells after transplantation. The hope is that these engineered HILOs can eventually be developed as a long term therapy for type 1 diabetes patients without the need for lifelong immunosuppression.
In a press release, the Salk researchers acknowledge that more research needs to be done before this system can be advanced to clinical trials. For example, the transplanted organoids need to be tested in mice for longer periods of time to confirm that their effects are long-lasting. More work needs to be done to ensure they would be safe to use in humans, as well. However, the proof of concept has now been established to move forward with these efforts. Concludes Dr. Evan’s in the announcement, “We now have a product that could potentially be used in patients without requiring any kind of device.”
Dr. Andrew Elfanty (left) and Dr. Ed Stanley (right), Murdoch Children’s Research Institute in Melbourne, Australia
Our immune system is the first line of defense our bodies use to fight off infections and disease. One crucial component of this defense mechanism are lymphocytes, which are specialized cells that give rise to various kinds of immune cells, such as a T cell, designed to attack and destroy harmful foreign bodies. Problems in how certain immune cells are formed can lead to diseases such as leukemia and other immune system related disorders.
But how exactly do immune cells form early on in the body?
Dr. Andrew Elfanty and Dr. Ed Stanley at Murdoch Children’s Research Institute in Australia have reproduced and visualized a method in the laboratory used to create human immune cells from pluripotent stem cells, a kind of stem cell that can make virtually any kind of cell in the body. Not only can this unlock a better understanding of leukemia and other immune related diseases, it could potentially lead to a patient’s own skin cells being used to produce new cells for cancer immunotherapy or to test autoimmune disease therapies.
Dr. Elefanty and Dr. Stanley used genetic engineering and a unique way of growing stem cells to make this discovery.
As observed in this video, the team was able to engineer pluripotent stem cells to glow green when they expressed a specific protein found in early immune cells. These cells can be seen migrating along blood vessels outlined in red. These cells go on to populate the thymus, which as we discussed in an earlier blog, is an organ that is crucial in developing functional T cells.
In a press release from Murdoch Children’s Research Institute, Dr. Stanley talks about the important role these early immune cells might play.
“We think these early cells might be important for the correct maturation of the thymus, the organ that acts as a nursery for T-cells”
In addition to this, the team also isolated the green, glowing pluripotent stem cells and showed that they could be used for multiple immune cell types, including those necessary for shaping the development of the immune system as a whole.
In the same press release, Dr. Elefanty discusses the future direction that their research could lead to.
“Although a clinical application is likely still years away, we can use this new knowledge to test ideas about how diseases like childhood leukemia and type 1 diabetes develop. Understanding more about the steps these cells go through, and how we can more efficiently nudge them down a desired pathway, is going to be crucial to that process.”
The full results to this study were published in Nature Cell Biology.
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.
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