Don’t Sugar Coat it: A Patient’s Perspective on Type 1 Diabetes

John Welsh

John Welsh

“In the weeks leading up to my diagnosis, I remember making and drinking Kool-Aid at the rate of about a gallon per day, and getting up to pee and drink Kool-Aid several times a night. The exhaustion and constant thirst and the weight loss were pretty scary. Insulin saved my life, and it’s been saving my life every day for the past 40 years.” – John Welsh

 

In honor of diabetes awareness month, we are featuring a patient perspective on what it’s like to live with type 1 diabetes (T1D) and what the future of stem cell research holds in terms of a cure.

T1D is a chronic disease that destroys the insulin producing cells in your pancreas, making it very difficult for your body to maintain the proper levels of sugar in your blood. There is no cure for T1D and patients take daily shots of insulin and closely monitor their blood sugar to stay healthy and alive.

Stem cell research offers an alternative strategy for treating T1D patients by potentially replacing their lost insulin producing cells. We’ve written blogs about ongoing stem cell research for diabetes on the Stem Cellar (here) but we haven’t focused on the patient side of T1D. So today, I’m introducing you to John Welsh, a man whose has lived with T1D since 1976.

John Welsh is a MD/PhD scientist and currently works at a company called Dexcom, which make a continuous glucose monitoring (CGM) device for diabetes patients. He is also an enrolled patient in CIRM-funded stem cell clinical trial (also funded by JDRF) for T1D sponsored by the company ViaCyte. The trial is testing a device containing stem cell-derived pancreatic cells that’s placed under the skin to act as a transplanted pancreas. You can learn more about it here.

I reached out to John to see if he wanted to share his story about living with diabetes. He was not only willing but enthusiastic to speak with me. As you will read later, one of John’s passions is a “good story”. And he sure told me a good one. So before you read on, I recommend grabbing some coffee or tea, going to a quiet room, and taking the time to enjoy his interview.


Q: Describe your career path and your current job.

JW: I went to college at UC Santa Cruz and majored in biochemistry and molecular biology. I then went into the medical scientist training program (combined MD/PhD program) at UC San Diego followed by research positions in cell biology and cancer biology at UC San Francisco and Novartis. I’ve been a medical writer specializing in medical devices for type 1 diabetes since 2009. At Dexcom, I help study the benefits of CGM and get the message out to healthcare professionals.

Q: How has diabetes affected your life and what obstacles do you deal with because of diabetes?

JW: I found out I had T1D at the age of 13, and it’s been a part of my life for 40 years. It’s been a big deal in terms of what I’m not allowed to do and figuring out what would be challenging if I tried. On the other hand, having diabetes is a great motivator on a lot of levels personally, educationally and professionally. Having this disease made me want to learn everything I could about the endocrine system. From there, my interests turned to biology – molecular biology in particular – and understanding how molecules in cells work.

The challenge of having diabetes also motivated me to do things that I might not have thought about otherwise – most importantly, a career that combined science and medicine. Having to stay close to my insulin and insulin-delivery paraphernalia (early on, syringes; nowadays, the pump and glucose monitor) meant that I couldn’t do as many ridiculous adventures as I might have otherwise.

Q: Did your diagnosis motivate you to pursue a scientific career?

JW: Absolutely. If I hadn’t gotten diabetes, I probably would have gone into something like engineering. But my parents were both healthcare professionals, so a career in medicine seemed plausible. The medical scientist MD/PhD training program at UC San Diego was really cool, but very competitive. Having first-hand experience with this disease may have given me an inside track with the admissions process, and that imperative – to understand the disease and how best to manage it – has been a great motivator.

There’s also a nice social aspect to being surrounded by people whose lives are affected by T1D.

Q: Describe your treatment regimen for T1D?

JW: I travel around with two things stuck on my belly, a Medtronic pump and a Dexcom Continuous Glucose Monitor (CGM) sensor. The first is an infusion port that can deliver insulin into my body. The port lasts for about three days after which you have to take it out. The port that lives under the skin surface is nine millimeters long and it’s about as thick as a mechanical pencil lead. The port is connected to a tube and the tube is connected to a pump, which has a reservoir with fast-acting insulin in it.

The insulin pump is pretty magical. It’s conceptually very simple, but it transforms the way a lot of people take insulin. You program it so that throughout the day, it squirts in a tiny bit of basal insulin at the low rate that you want. If you’re just cruising through your day, you get an infusion of insulin at a low basal rate. At mealtimes, you can give yourself an extra squirt of insulin like what happens with normal people’s pancreas. Or if you happen to notice that you have a high sugar level, you can program a correction bolus which will help to bring it back to towards the normal range. The sensor continuously interrogates the glucose concentration in under my skin. If something goes off the rails, it will beep at me.

dexcom_g4_platinum_man

Dexcom continuous glucose monitor.

As good as these devices are, they’re not a cure, they’re not perfect, and they’re not cheap, so one of my concerns as a physician and as a patient is making these transformative devices better and more widely available to people with the disease.

Q: What are the negative side effects associated with your insulin pump and sensor?

JW:  If you have an insulin pump, you carry it everywhere because it’s stuck onto you. The pump is on you for three days and it does get itchy. It’s expensive and a bit uncomfortable. And when I take my shirt off, it’s obvious that I have certain devices stuck on me.  This is a big disincentive for some of my type 1 friends, especially those who like to wear clothes without pockets. And every once-in-a-while, the pump will malfunction and you need a backup plan for getting insulin when it breaks.

On the other hand, the continuous glucose monitoring (CGM) is wonderful especially for moms and dads whose kids have T1D. CGM lets parents essentially spy on their kids. You can be on the sidelines watching your kid play soccer and you get a push notification on your phone saying that the glucose concentration is low, or is heading in that direction. The best-case scenario is that this technology helps people avoid dangerous and potentially catastrophic low blood sugars.

Q: Was the decision easy or hard to enroll in the ViaCyte trial?

JW: It was easy! I was very excited to learn about the ViaCyte trial and equally pleased to sign up for it. When I found out about it from a friend, I wanted to sign up for it right away. I went to clinicaltrials.gov and contacted the study coordinator at UC San Diego. They did a screening interview over the phone, and then they brought me in for screening lab work. After I was selected to be in the trial, they implanted a couple of larger devices (about the size of a credit card) under the skin of my lower back, and smaller devices (about the size of a postage stamp) in my arm and lower back to serve as “sentinels” that were taken out after two or three months.

ViaCyte device

ViaCyte device

I’m patient number seven in the safety part of this trial. They put the cell replacement therapy device in me without any pre-medication or immunosuppression. They tested this device first in diabetic mice and found that the stem cells in the device differentiated into insulin producing cells, much like the ones that usually live in the mouse pancreas. They then translated this technology from animal models to human trials and are hoping for the same type of result.

I had the device transplanted in March of 2015, and the plan is for in the final explant procedure to take place next year at the two-year anniversary. Once they take the device out, they will look at the cells under the microscope to see if they are alive and whether they turned into pancreatic cells that secrete insulin.

It’s been no trouble at all having this implant. I do clinic visits regularly where they do a meal challenge and monitor my blood sugar. My experience being a subject in this clinical study has been terrific. I met some wonderful people and I feel like I’m helping the community and advancing the science.

Q: Do you think that stem cell-derived therapies will be a solution for curing diabetes?

JW: T1D is a great target for stem cell therapy – the premise makes a lot of sense — so it’s logical that it’s one of the first ones to enter clinical trials. I definitely think that stem cells could offer a cure for T1D. Even 30 years ago, scientists knew that we needed to generate insulin producing cells somehow, protect them from immunological rejection, and package them up and put them somewhere in the body to act like a normal pancreas. The concept is still a good concept but the devil is in the implementation. That’s why clinical trials like the one CIRM is funding are important to figure these details out and advance the science.

Q: What is your opinion about the importance of stem cell research and advancing stem cell therapies into clinical trials?

JW: Understanding how cells determine their fate is tremendously important. I think that there’s going to be plenty of payoffs for stem cell research in the near term and more so in the intermediate and long term. Stem cell research has my full support, and it’s fun to speculate on how it might address other unmet medical needs. The more we learn about stem cell biology the better.

Q: What advice do you have for other patients dealing with diabetes or who are recently diagnosed?

JW: Don’t give up, don’t be ashamed or discouraged, and gather as much data as you can. Make sure you know where the fast-acting carbohydrates are!

Q: What are you passionate about?

JW: I love a good story, and I’m a fan of biological puzzles. It’s great having a front-row seat in the world of diabetes research, and I want to stick around long enough to celebrate a cure.


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Throwback Thursday: Progress to a Cure for Type 1 Diabetes

Welcome back to our “Throwback Thursday” series on the Stem Cellar. Over the years, we’ve accumulated an arsenal of valuable stem cell stories on our blog. Some of these stories represent crucial advances towards stem cell-based cures for serious diseases and deserve a second look.

novemberawarenessmonthThis week in honor of Diabetes Awareness Month, we are featuring type 1 diabetes (T1D), a chronic disease that destroys the insulin-producing beta cells in your pancreas. Without these important cells, patients cannot maintain the proper levels of glucose, a fancy name for sugar, in their blood and are at risk for many complications including heart disease, blindness, and even death.

Cell replacement therapy is evolving into an attractive option for patients with T1D. Replacing lost beta cells in the pancreas is a more permanent and less burdensome solution than the daily insulin shots (or insulin pumps) that many T1D patients currently take.

So let’s take a look at the past year’s advances in stem cell research for diabetes.

Making Insulin-Producing Cells from Stem Cells and Skin

This year, there were a lot of exciting studies that improved upon previous methods for generating pancreatic beta cells in a dish. Here’s a brief recap of a few of the studies we covered on our blog:

  • Make pancreatic cells from stem cells. Scientists from the Washington University School of Medicine in St. Louis and the Harvard Stem Cell Institute developed a method that makes beta cells from T1D patient-derived induced pluripotent stem cells (iPSCs) that behave very similarly to true beta cells both in a dish and when transplanted into diabetic mice. Their discovery has the potential to offer personalized stem cell treatments for patients with T1D in the near future and the authors of the study predicted that their technology could be ready to test in humans in the next three to five years.
  • Making functional pancreatic cells from skin. Scientists from the Gladstone Institutes used a technique called direct reprogramming to turn human skin cells directly into pancreatic beta cells without having to go all the way back to a pluripotent stem cell state. The pancreatic cells looked and acted like the real thing in a dish (they were able to secrete insulin when exposed to glucose), and they functioned normally when transplanted into diabetic mice. This study is exciting because it offers a new and more efficient method to make functioning human beta cells in mass quantities.

    Functioning human pancreatic cells after they’ve been transplanted into a mouse. (Image: Saiyong Zhu, Gladstone)

    Functioning human pancreatic cells after they’ve been transplanted into a mouse. (Image: Saiyong Zhu, Gladstone)

  • Challenges of stem cell-derived diabetes treatments. At this year’s Ogawa-Yamanaka Stem Cell Award ceremony Douglas Melton, a well-renowned diabetes researcher from Harvard, spoke about the main challenges for developing stem cell-derived diabetes treatments. The first is the need for better control over the methods that make beta cells from stem cells. The second was finding ways to make large quantities of beta cells for human transplantation. The last was finding ways to prevent a patient’s immune system from rejecting transplanted beta cells. Melton and other scientists are already working on improving techniques to make more beta cells from stem cells. As for preventing transplanted beta cells from being attacked by the patient’s immune system, Melton described two possibilities: using an encapsulation device or biological protection to mask the transplanted cells from an attack.

Progress to a Cure: Clinical Trials for Type 1 Diabetes

Speaking of encapsulation devices, CIRM is funding a Phase I clinical trial sponsored by a San Diego-based company called ViaCyte that’s hoping to develop a stem cell-based cure for patients with T1D. The treatment involves placing a small encapsulated device containing stem cell-derived pancreatic precursor cells under the skin of T1D patients. Once implanted, these precursor cells should develop into pancreatic beta cells that can secrete insulin into the patient’s blood stream. The goal of this trial is first to make sure the treatment is safe for patients and second to see if it’s effective in improving a patient’s ability to regulate their blood sugar levels.

To learn more about this exciting clinical trial, watch this fun video made by Youreka Science.

ViaCyte is still waiting on results for their Phase 1 clinical trial, but in the meantime, they are developing a modified version of their original device for T1D called PEC-Direct. This device also contains pancreatic precursor cells but it’s been designed in a way that allows the patient’s blood vessels to make direct connections to the cells inside the device. This vascularization process hopefully will improve the survival and function of the insulin producing beta cells inside the device. This study, which is in the last stage of research before clinical trials, is also being funded by CIRM, and we are excited to hear news about its progress next year.

ViaCyte's PEC-Direct device allows a patient's blood vessels to integrate and make contact with the transplanted beta cells.

ViaCyte’s PEC-Direct device allows a patient’s blood vessels to integrate and make contact with the transplanted beta cells.


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CIRM Board targets diabetes and kidney disease with big stem cell research awards

diabetes2

A recent study  estimated there may be more than 500 million people worldwide who have diabetes. That’s an astounding figure and makes diabetes one of the largest chronic disease epidemics in human history.

One of the most serious consequences of untreated or uncontrolled diabetes is kidney damage. That can lead to fatigue, weakness, confusion, kidney failure and even death. So two decisions taken by the CIRM Board today were good news for anyone already suffering from either diabetes or kidney disease. Or both.

The Board awarded almost $10 million to Humacyte to run a Phase 3 clinical trial of an artificial vein needed by people undergoing hemodialysis – that’s the most common form of dialysis for people with kidney damage. Hemodialysis helps clean out impurities and toxins from the blood. Without it waste will build up in the kidneys with devastating consequences.

The artificial vein is a kind of bioengineered blood vessel. It is implanted in the individual’s arm and, during dialysis, is connected to a machine to move the blood out of the body, through a filter, and then back into the body. The current synthetic version of the vein is effective but is prone to clotting and infections, and has to be removed regularly. All this puts the patient at risk.

Humacyte’s version – called a human acellular vessel or HAV – uses human cells from donated aortas that are then seeded onto a biodegradable scaffold and grown in the lab to form the artificial vein. When fully developed the structure is then “washed” to remove all the cellular tissue, leaving just a collagen tube. That is then implanted in the patient, and their own stem cells grow onto it, essentially turning it into their own tissue.

In earlier studies Humacyte’s HAV was shown to be safer and last longer than current versions. As our President and CEO, Randy Mills, said in a news release, that’s clearly good news for patients:

“This approach has the potential to dramatically improve our ability to care for people with kidney disease. Being able to reduce infections and clotting, and increase the quality of care the hemodialysis patients get could have a significant impact on not just the quality of their life but also the length of it.”

There are currently almost half a million Americans with kidney disease who are on dialysis. Having something that makes life easier, and hopefully safer, for them is a big plus.

The Humacyte trial is looking to enroll around 350 patients at three sites in California; Sacramento, Long Beach and Irvine.

While not all people with diabetes are on dialysis, they all need help maintaining healthy blood sugar levels, particularly people with type 1 diabetes. That’s where the $3.9 million awarded to ViaCyte comes in.

We’re already funding a clinical trial with ViaCyte  using an implantable delivery system containing stem cell-derived cells that is designed to measure blood flow, detect when blood sugar is low, then secrete insulin to restore it to a healthy level.

This new program uses a similar device, called a PEC-Direct. Unlike the current clinical trial version, the PEC-Direct allows the patient’s blood vessels to directly connect, or vasularize, with the cells inside it. ViaCyte believes this will allow for a more robust engraftment of the stem cell-derived cells inside it and that those cells will be better able to produce the insulin the body needs.

Because it allows direct vascularization it means that people who get the delivery system  will also need to get chronic immune suppression to stop their body’s immune system attacking it. For that reason it will be used to treat patients with type 1 diabetes that are at high risk for acute complications such as severe hypoglycemic (low blood sugar) events associated with hypoglycemia unawareness syndrome.

In a news release Paul Laikind, Ph.D., President and CEO of ViaCyte, said this approach could help patients most at risk.

“This high-risk patient population is the same population that would be eligible for cadaver islet transplants, a procedure that can be highly effective but suffers from a severe lack of donor material. We believe PEC-Direct could overcome the limitations of islet transplant by providing an unlimited supply of cells, manufactured under cGMP conditions, and a safer, more optimal route of administration.”

The Board also approved more than $13.6 million in awards under our Discovery program. You can see the winners here.

 

Scientists Make Insulin-Secreting Cells from Stem Cells of Type 1 Diabetes Patients

Stem cell research for diabetes is in a Golden Age. In the past few years, scientists have developed methods to generate insulin-secreting pancreatic beta cell-like cells from embryonic stem cells, induced pluripotent stem cells (iPS cells), and even directly from human skin. We’ve covered a number of recent studies in this area on our blog, and you can read more about them here.

Patients with type 1 diabetes (T1D) suffer from an autoimmune response that attacks and kills the beta cells in their pancreas. Without these important cells, patients can no longer secrete insulin in response to increased glucose or sugar levels in the blood. Cell replacement is evolving into an attractive therapeutic option for patients with T1D. Replacing lost beta cells in the pancreas is a more permanent and less burdensome solution than the daily insulin shots that many T1D patients currently take.

Cell replacement therapy for type 1 diabetes

Stem cells are the latest strategy that scientists are pursuing for T1D cell replacement therapy. The strategy involves generating beta cells from pluripotent stem cells, either embryonic or iPS cells, that function similarly to beta cells found in a healthy human pancreas. Making beta cells from a patient’s own iPS cells is the ideal way to go because this autologous form (self to self) of transplantation would reduce the chances  of transplant rejection because a patient’s own cells would be put back into their body.

Scientists have generated beta cell-like cells from iPS cells derived from T1D patients previously, but the biological nature and function of these cells wasn’t up to snuff in a side by side comparison with beta cells from non-diabetic patients. They didn’t express the appropriate beta cell markers and failed to secrete the appropriate levels of insulin when challenged in a dish and when transplanted into animal models.

However, a new study published yesterday in Nature Communications has overcome this hurdle. Teams from the Washington University School of Medicine in St. Louis and the Harvard Stem Cell Institute have developed a method that makes beta cells from T1D patient iPS cells that behave very similarly to true beta cells. This discovery has the potential to offer personalized stem cell treatments for patients with T1D in the near future.

These beta cells could be the real deal

Their current work is based off of an earlier 2014 study – from the lab of Douglas Melton at Harvard – that generated functional human beta cells from both embryonic and iPS cells of non-diabetic patients. In the current study, the authors were interested in learning whether it was possible to generate functional beta cells from T1D patients and whether these cells would be useful for transplantation given that they could potentially be less functional than non-diabetic beta cells.

The study’s first author, Professor Jeffrey Millman from the Washington University School of Medicine, explained:

Jeffrey Millman

Jeffrey Millman

“There had been questions about whether we could make these cells from people with type 1 diabetes. Some scientists thought that because the tissue would be coming from diabetes patients, there might be defects to prevent us from helping the stem cells differentiate into beta cells. It turns out that’s not the case.”

After generating beta cells from T1D iPS cells, Millman and colleagues conducted a series of experiments to test the beta cells both in a dish and in mice. They found that the T1D-derived beta cells expressed the appropriate beta cell markers, secreted insulin in the presence of glucose, and responded well to anti-diabetic drugs that stimulated the beta cells to secrete even more insulin.

When T1D beta cells were transplanted into mice that lacked an immune system, they survived and functioned similarly to transplanted non-diabetic beta cells. When the mice were treated with a drug that killed off their mouse beta cells, the surviving human T1D beta cells were successful in regulating the blood glucose levels in the mice and kept them alive.

Beta cells derived from type 1 diabetes patient stem cells (top) express the same beta cell markers as beta cells derived from non-diabetic (ND) patients.

Beta cells derived from type 1 diabetes patient stem cells (top) express the same beta cell markers as beta cells derived from non-diabetic (ND) patients. (Nature Communications)

Big Picture

The authors concluded that the beta cells they generated from T1D iPS cells were indistinguishable from healthy beta cells derived from non-diabetic patients. In a news release, Millman commented on the big picture of their study:

“In theory, if we could replace the damaged cells in these individuals with new pancreatic beta cells — whose primary function is to store and release insulin to control blood glucose — patients with type 1 diabetes wouldn’t need insulin shots anymore. The cells we’ve manufactured sense the presence of glucose and secrete insulin in response. And beta cells do a much better job controlling blood sugar than diabetic patients can.”

He further commented that the T1D- derived beta cells “could be ready for human research in three to five years. At that time, Millman expects the cells would be implanted under the skin of diabetes patients in a minimally invasive surgical procedure that would allow the beta cells access to a patient’s blood supply.”

“What we’re envisioning is an outpatient procedure in which some sort of device filled with the cells would be placed just beneath the skin,” he said.

In fact, such devices already exist. CIRM is funding a type 1 diabetes clinical trial sponsored by the San Diego based company ViaCyte. They are currently testing a combination drug delivery system that implants a medical device capsule containing pancreatic progenitor cells derived from human embryonic stem cells. Once implanted, the progenitor cells are expected to specialize into mature pancreatic cells including beta cells that secrete insulin.


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Type 1 Diabetes Trial Explained Whiteboard Video Style

There’s a saying, a picture is worth a thousand words. With complicated science however, pictures don’t always do these topics justice. Here’s where videos come to the rescue.

Florie Mar, founder of Youreka Science.

Florie Mar, founder of Youreka Science.

Today’s topic is type 1 diabetes and a CIRM-funded clinical trial headed by the San Diego company ViaCyte hoping to develop a cure for patients with this disease. Instead of writing an entire blog about the latest on this clinical trial, we are featuring an excellent video by Youreka Science. This nonprofit organization is the brainchild of former University of California, San Francisco graduate student Florie Mar who has a passion to bring scientific concepts to life to reach both students and the general public.

Youreka’s style uses whiteboard videos to explain disease and basic science research with drawings, words, and lay person-friendly narrative. This particular video, “Progress and Promise of Stem Cell Research: Type 1 Diabetes” was developed in collaboration with Americans for Cures and explains how CIRM-funded stem cell research is “leading to groundbreaking advances in diabetes.”

We are also excited about this ViaCyte trial as it’s being conducted in one of the CIRM Alpha Stem Cell Clinics located at the University of California, San Diego. The goal of the Alpha Clinics is to accelerate the development and delivery of stem cell therapies to patients by providing stem-cell focused clinics for conducting high quality trials.

In brief, the video explains ViaCyte’s stem cell derived therapy that replaces the insulin-producing cells that are lost in type 1 diabetes patients. For more details, check out the video!

 

And to hear from Viacyte’s chief scientific officer as well as two people living with type 1 diabetes, check out a CIRM video we produced a few years ago.


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The best scientists always want to know more

Sir Isaac Newton

Sir Isaac Newton

Some years ago I was in the Wren Library at Trinity College, Cambridge in England when I noticed a display case with a cloth over it. Being a naturally curious person, downright nosy in fact, I lifted the cloth. In the display case was a first edition of Sir Isaac Newton’s Principia Mathematica and in the margins were notes, corrections put there by Newton for the second edition.

It highlighted for me how the best scientists never stop working, never stop learning, never stop trying to improve what they do.

That came back to me when I saw a news release from ViaCyte, a company we are funding in a Phase 1 clinical trial to treat type 1 diabetes.  The news release announced results of a study showing that insulin-producing cells, created in the lab from embryonic stem cells, can not only mature but also function properly after being implanted in a capsule-like device and placed under the skin of an animal model.

VC-01-cross-section-5

Now the clinical trial we are funding with ViaCyte uses a similar, but slightly different set of cells in people. The device in the trial contains what ViaCyte calls PEC-01™ pancreatic progenitor cells. These are essentially an earlier stage of the mature pancreatic cells that our body uses to produce insulin. The hope is that when implanted in the body, the cells will mature and then behave like adult pancreatic cells, secreting insulin and other hormones to keep blood glucose levels stable and healthy.

Those cells and that device are being tested in people with type 1 diabetes right now.

Learning more

But in this study ViaCyte wanted to know if beta cells, a more mature version of the cells they are using in our trial, would also work or have any advantages over their current approach.

The good news, published in the journal Stem Cells Translational Medicine,  is that these cells did work. As they say in their news release:

“The animal study also demonstrated for the first time that when encapsulated in a device and implanted into mice, these more mature cells are capable of producing functional pancreatic beta cells. ViaCyte is also the first to show that these further differentiated cells can function in vivo following cryopreservation, a valuable process step when contemplating clinical and commercial application.”

This does not mean ViaCyte wants to change the cells it uses in the clinical trial. As President and CEO Paul Laikind, PhD, makes clear:

“For a number of reasons we believe that the pancreatic progenitor cells that are the active component of the VC01 product candidate are better suited for cell replacement therapy. However, the current work has expanded our fundamental knowledge of beta cell maturation and could lead to further advances for the field.”

And that’s what I mean about the best scientists are the ones who keeping searching, keeping looking for answers. It may not help them today, but who knows how important that work will prove in the future.

Moving one step closer to a therapy for type 1 diabetes

When I was a medical journalist one word I always shied away from was “breakthrough”. There are few true breakthroughs in medicine. Usually any advance is the result of years and years of work. That’s why good science takes time; it takes hundreds of small steps to make a giant leap forward.

Today we took one of those steps. ViaCyte, a company we have supported for many years, just announced that the first patient has been successfully implanted with a device designed to help treat type 1 diabetes.

It’s an important milestone for the company, for us, and of course for people with type 1 diabetes. As Dr. Paul Laikind, the President and CEO of ViaCyte, said in a news release, this is an exciting moment:

“To our knowledge, this is the first time that an embryonic stem cell-derived cell replacement therapy for diabetes has been studied in human subjects, and it represents the culmination of a decade of effort by the ViaCyte team, our collaborators, and our supporters at the California Institute for Regenerative Medicine and at JDRF.”

The VC-01 device is being tested in a clinical trial at the University of California, San Diego Health System. There are two goals; first to see if it is safe; and secondly to see if it helps patients who have type 1 diabetes. When the device is implanted under the skin the cells inside are able to sense when blood sugar is high and, in response, secrete insulin to restore it to a healthy level.

The beauty of the VC-01 is that while it lets cells secrete insulin out, it prevents the body’s own immune system from getting in and attacking the cells.

The device is about the length and thickness of a credit card but only half as wide which makes it easy to implant under the skin.

Today’s news, that this is now truly out of the lab and being tested in patients is an important step in a long road to showing that it works in patients. The people at ViaCyte, who have been working hard on this project for many years, know that they still have a long way to go but for today at least, this step probably feels a little bit more like a skip for joy.

Scientists Reach Yet Another Milestone towards Treating Type 1 Diabetes

There was a time when having type 1 diabetes was equivalent to a death sentence. Now, thanks to advances in science and medicine, the disease has shifted from deadly to chronic.

But this shift, doctors argue, is not good enough. The disease still poses significant health risks, such as blindness and loss of limbs, as the patients get older. There has been a renewed effort, therefore, to develop superior therapies—and those based on stem cell technology have shown significant promise.

Human stem cell-derived beta cells that have formed islet like clusters in a mouse. Cells were transplanted to the kidney capsule and photo was taken two weeks later by which time the beta cells are making insulin and have cured the mouse's diabetes. [Credit: Douglas Melton]

Human stem cell-derived beta cells that have formed islet like clusters in a mouse. Cells were transplanted to the kidney capsule and photo was taken two weeks later by which time the beta cells are making insulin and have cured the mouse’s diabetes. [Credit: Douglas Melton]

Indeed, CIRM-funded scientists at San Diego-based Viacyte, Inc. recently received FDA clearance to begin clinical trials of their VC-01 product candidate that delivers insulin via healthy beta cells contained in a permeable, credit card-sized pouch.

And now, scientists at Harvard University have announced a technique for producing mass quantities of mature beta cells from embryonic stem cells in the lab. The findings, published today in the journal Cell, offer additional hope for the millions of patients and their families looking for a better way to treat their condition.

The team’s ability to generate billions of healthy beta cells—cells within the pancreas that produce insulin in order to maintain normal glucose levels—has a particular significance to the study’s senior author and co-scientific director of the Harvard Stem Cell Institute, Dr. Doug Melton. 23 years ago, his infant son Sam was diagnosed with type 1 diabetes and since that time Melton has dedicated his career to finding better therapies for his son and the millions like him. Melton’s daughter, Emma, has also been diagnosed with the disease.

Type 1 diabetes is an autoimmune disorder in which the body’s immune system systematically targets and destroys the pancreas’ insulin-producing beta cells.

In this study, the team took human embryonic stem cells and transformed them into healthy beta cells. They then transplanted them into mice that had been modified to mimic the signs of diabetes. After closely monitoring the mice for several weeks, they found that their diabetes was essentially ‘cured.’ Said Melton:

“You never know for sure that something like this is going to work until you’ve tested it numerous ways. We’ve given these cells three separate challenges with glucose in mice and they’ve responded appropriately; that was really exciting.”

The researchers are undergoing additional pre-clinical studies in animal models, including non-human primates, with the hopes that the 150 million cells required for transplantation are also protected from the body’s immune system, and not destroyed.

Melton’s team is collaborating with Medical Engineer Dr. Daniel G. Anderson at MIT to develop a protective implantation device for transplantation. Said Anderson of Melton’s work:

“There is no question that the ability to generate glucose-responsive, human beta cells through controlled differentiation of stem cells will accelerate the development of new therapeutics. In particular, this advance opens the doors to an essentially limitless supply of tissue for diabetic patients awaiting cell therapy.”

Stem Cell Agency Funded Treatment for Type 1 Diabetes Takes a Big Step towards Clinical Trials

Even the best ideas can fail without a lot of support. One of the things we pride ourselves on at the Stem Cell Agency is nurturing really promising ideas for new therapies through sustained funding, giving them the support they need to turn that promise into reality. So it’s very gratifying today to hear that one project we have supported for many years, ViaCyte’s VC-01™ implantable device for treating type 1 diabetes, just took a big step towards being tested in patients.

ViaCyte has submitted what’s called an Investigational New Drug application (“IND”) with the Food and Drug Administration (FDA) asking permission to start a phase 1/2 clinical trial in patients. If the FDA says yes then ViaCyte hopes to start testing their device in patients before the end of the year.

We have invested almost $40 million in nurturing the project through the early, most basic research to see if this approach could be made to work, and then through more rigorous advanced research and testing in animals to make sure it’s safe and that it is effective.

As our Chairman, Jonathan Thomas, says in a press release we sent out announcing the news:

“We have been strong supporters of Viacyte for many years and it’s great to see that they are well on the way to starting a First-in-Human trial, hopefully in the next few months. This therapy’s growth from an idea to a potential treatment highlights CIRM’s commitment to following promising science at all stages of development.”

The device is really quite ingenious. It is a thin plastic pouch that contains an immature form of pancreatic cells. When the device is implanted under the skin these cells become the different kinds of cells needed to regulate blood glucose levels. They are able to sense when blood glucose is high, and then secrete insulin to restore it to a healthy level. The truly impressive part is that the device has holes large enough to allow insulin to be pushed out, but too small to allow the body’s own immune system to get in and attack the device.

The goal of the first phase of this clinical trial, as with all phase 1 trials, is simply to show that the VC-01™ is safe. The second phase will also look at safety but also test it to see if it is helping patients, reducing their dependence on injected insulin. If the results from both those phases are encouraging, the next step is to test it in much larger numbers of patients to see just how effective it is.

But this first step, submitting an application to the FDA, is the starting point for all that. As our President and CEO C. Randal Mills said in our news release, getting to the starting line is often half the battle:

“This is good news for ViaCyte and is an encouraging sign of the progress they are making. Filing for an IND is a crucial step along the path to making a therapy available to patients and we’ll be working with them and supporting them every step of the way to try and make this happen as quickly, and as safely, as possible.”

You can read more about ViaCyte and our support for them on our website.