Good news from Asterias’ CIRM-funded spinal cord injury trial

This week in the stem cell field, all eyes are on Asterias Biotherapeutics, a California-based company that’s testing a stem cell based-therapy in a CIRM-funded clinical trial for spinal cord injury patients. The company launched its Phase 1/2a clinical trial back in 2014 with the goal of determining the safety of the therapy and the optimal dose of AST-OPC1 cells to transplant into patients.

astopc1AST-OPC1 cells are oligodendrocyte progenitor cells derived from embryonic stem cells. These are cells located in the brain and spinal cord that develop into support cells that help nerve cells function and communicate with each other.

Asterias is transplanting AST-OPC1 cells into patients that have recently suffered from severe spinal cord injuries in their neck. This type of injury leaves patients paralyzed without any feeling from their neck down. By transplanting cells that can help the nerve cells at the injury site reform their connections, Asterias hopes that their treatment will allow patients to regain some form of movement and feeling.

And it seems that their hope is turning into reality. Yesterday, Asterias reported in a news release that five patients who received a dose of 10 million cells showed improvements in their ability to move after six months after their treatment. All five patients improved one level on the motor function scale, while one patient improved by two levels. A total of six patients received the 10 million cell dose, but so far only five of them have completed the six-month follow-up study, three of which have completed the nine-month follow-up study.

We’ve profiled two of these six patients previously on the Stem Cellar. Kris Boesen was the first patient treated with 10 million cells and has experienced the most improvement. He has regained the use of his hands and arms and can now feed himself and lift weights. Local high school student, Jake Javier, was the fifth patient in this part of the trial, and you can read about his story here.

Kris Boesen, CIRM spinal cord injury clinical trial patient.

Kris Boesen, CIRM spinal cord injury clinical trial patient.

jake_javier_stories_of_hope

Jake Javier and his Mom

The lead investigator on this trial, Dr. Richard Fessler, explained the remarkable progress that these patients have made since their treatment:

“With these patients, we are seeing what we believe are meaningful improvements in their ability to use their arms, hands and fingers at six months and nine months following AST-OPC1 administration. Recovery of upper extremity motor function is critically important to patients with complete cervical spinal cord injuries, since this can dramatically improve quality of life and their ability to live independently.”

Asterias will continue to monitor these patients for changes or improvements in movement and will give an update when these patients have passed the 12-month mark since their transplant. However, these encouraging preliminary results have prompted the company to look ahead towards advancing their treatment down the regulatory approval pathway, out of clinical trials and into patients.

Asterias CEO, Steve Cartt, commented,

Steve Cartt, CEO of Asterias Biotherapeutics

Steve Cartt, CEO of Asterias Biotherapeutics

“These results to date are quite encouraging, and we look forward to initiating discussions with the FDA in mid-2017 to begin to determine the most appropriate clinical and regulatory path forward for this innovative therapy.”

 

Talking with the US FDA will likely mean that Asterias will need to show further proof that their stem cell-based therapy actually improves movement in patients, rather than the patients spontaneously regaining movement (which has been observed in patients before). FierceBiotech made this point in a piece they published yesterday on this trial.

“Those discussions with FDA could lead to a more rigorous examination of the effect of AST-OPC1. Some patients with spinal injury experience spontaneous recovery. Asterias has put together matched historical data it claims show “a meaningful difference in the motor function recovery seen to date in patients treated with the 10 million cell dose of AST-OPC1.” But the jury will remain out until Asterias pushes ahead with plans to run a randomized controlled trial.”

In the meantime, Asterias is testing a higher dose of 20 million AST-OPC1 cells in a separate group of spinal cord injury patients. They believe this number is the optimal dose of cells for achieving the highest motor improvement in patients.

2017 will bring more results and hopefully more good news about Asterias’ clinical trial for spinal cord injury. And as always, we’ll keep you informed with any updates on our Stem Cellar Blog.

Stem Cell Profiles in Courage: Karl’s Fight with Cancer

Karl Trede

Karl Trede

When I think of a pioneer I have an image in my head of people heading west across the Americans plains in the 18th century, riding in a covered wagon pulled by weary oxen.

Karl Trede doesn’t fit that image at all. He is a trim, elegant man who has a ready smile and a fondness for Hawaiian shirts. But he is no less a pioneer for all that. That’s why we profiled him in our 2016 Annual Report.

In 2006 Karl was diagnosed with cancer of the throat. He underwent surgery to remove his vocal chords and thought he had beaten the cancer. A few years later, it came back. That was when Karl became the first person ever treated in a CIRM-funded clinical trial testing a new anti-tumor therapy targeting cancer stem cells that so far has helped hold the disease at bay.

Here is Karl’s story, in his own words:

“I had some follow-up tests and those showed spots in my lungs. Over the course of several years, they saw those spots grow, and we knew the cancer had spread to my lungs. I went to Stanford and was told there was no effective treatment for it, fortunately it was slow growing.

Then one day they said we have a new clinical trial we’re going to start would you be interested in being part of it.

I don’t believe I knew at the time that I was going to be the first one in the trial [now that’s what I call a pioneer] but I thought I’d give it a whirl and I said ‘Sure’. I wasn’t real concerned about being the first in a trial never tested in people before. I figured I was going to have to go someday so I guess if I was the first person and something really went wrong then they’d definitely learn something; so, to me, that was kind of worth my time.

Fortunately, I lasted 13 months, 72 treatments with absolutely no side effects. I consider myself really lucky to have been a part of it.

It was an experience for me, it was eye opening. I got an IV infusion, and the whole process was 4 hours once a week.

Dr. Sikic (the Stanford doctor who oversees the clinical trial) made it a practice of staying in the room with me when I was getting my treatments because they’d never tried it in people, they’d tested it in mice, but hadn’t tested it in people and wanted to make sure they were safe and nothing bad happened.

The main goals of the trial were to define what the side effects were and what the right dose is and they got both of those. So I feel privileged to have been a part of this.

My wife and I (Vita) have four boys. They’re spread out now – two in the San Francisco Bay Area, one in Oregon and one in Nevada. But we like to get together a few times a year. They’re all good cooks, so when we have a family get together there’s a lot of cooking involved.

The Saturday after Thanksgiving, in 2015, the boys decided they wanted to have a rib cook-off for up to around 30 people and I can proudly say that I kicked their ass on the rib cook-off. I have an electric cooker and I just cook ‘em slow and long. I do a cranberry sauce, just some home made bbq sauces

I’m a beef guy, I love a good steak, a good ribeye or prime rib, I make a pretty mean Oso bucco, I make a good spaghetti sauce, baked chicken with an asparagus mousse that is pretty good.

I just consider myself a lucky guy.”

Karl Trede with CIRM President Randy Mills at the 2016 December Board meeting.

Karl Trede with CIRM President Randy Mills at the 2016 December Board meeting.


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Genetically engineered immune cells melt away deadly brain tumors

MRI scan of patient with glioblastoma tumor. (wikicommons)

MRI scan of patient with glioblastoma. (wikicommons)

Cancers come in many different forms. Some are treatable if caught early and other aren’t. One of the most deadly types of cancers are glioblastomas – a particularly aggressive form of brain tumor.  Patients diagnosed with glioblastoma have an average life expectancy of 12-15 months and there is no cure or effective treatment that extends life.

While a glioblastoma diagnosis has pretty much been a death sentence, now there could be a silver lining to this deadly, fast-paced disease. Last week, scientists from the City of Hope in southern California reported in the New England Journal of Medicine, a new cell-based therapy that melted away brain tumors in a patient with an advanced stage of glioblastoma.

An Immunotherapy Approach to Glioblastoma

The patient is a 50-year-old man named Richard Grady who was participating in an investigational clinical trial run out of the City of Hope’s CIRM Alpha Stem Cell Clinic. A brain scan revealed a brightly lit tumor on the right side of Richard’s brain. Doctors surgically removed the tumor and treated him with radiation in an attempt to staunch further growth. But after six months, the tumors came back with a vengeance, spreading to other parts of his brain, lighting up his MRI scan like a Christmas tree.

With few treatment options and little time left, Richard was enrolled in the City of Hope trial that was testing a cell-based immunotherapy that recognizes and attacks cancer cells. It’s called CAR T-cell therapy – a term that you probably have heard in the news as a promising and cutting-edge treatment for cancer. Scientists extract immune cells, called T-cells, from a patient’s blood and reengineer them in the laboratory to recognize unique surface markers on cancer cells. These specialized CAR T-cells are then put back into the patient to attack and kill off cancer cells.

In Richard’s case, CAR-T cells were first infused into his brain through a tube in an area where a tumor was recently removed. No new tumors grew in that location of his brain, but tumors in other areas continued to grow and spread to his spinal cord. At this point, the scientists decided to place a second tube into a cavity of the brain called the ventricles, which contain a clear liquid called cerebrospinal fluid. Directly infusing into the spinal fluid allowed the cancer fighting cells to travel to different parts of the brain and spinal cord to attack the tumors.

Behnam Badie, senior author on the study and neurosurgery chief at the City of Hope, explained in a news release,

Benham Badie, City of Hope

Benham Badie, City of Hope

“By injecting the reengineered CAR-T cells directly into the tumor site and the ventricles, where the spinal fluid is made, the treatment could be delivered throughout the patient’s brain and also to the spinal cord, where this particular patient had a large metastatic tumor.”

 

Bye Bye Brain Tumors? Almost…

Three infusions of the CAR T-cell treatment shrunk Richard’s tumors noticeably, and a total of ten infusions was enough to melt away Richard’s tumors completely. Amazingly, Richard was able to reduce his medications and go back to work.

TESt

CAR T-cell therapy reduces brain tumors when infused into the spinal fluid. (NEJM)

The effects of the immunotherapy lasted for seven-and-a-half months. Unfortunately, his glioblastoma did come back, and he is now undergoing radiation treatment. Instead of being discouraged by these results, we should be encouraged. Patients with advanced cases of glioblastoma like Richard often have only weeks left to live, and the prospect of another seven months of life with family and friends is a gift.

Following these promising results in a single patient, the City of Hope team has now treated a total of nine patients in their clinical trial. Their initial results indicate that the immunotherapy is relatively safe. Further studies will be done to determine whether this therapy will be effective at treating other types of cancers.

CIRM Alpha Clinics Advance Stem Cell Treatments

The findings in this study are particularly exciting to CIRM, not only because they offer a new treatment option for a deadly brain cancer, but also because the clinical trial testing this treatment is housed at one of our own Alpha Clinics. In 2014, CIRM funded three stem cell-focused clinics at the City of Hope, UC San Diego, and a joint clinic between UC Los Angeles and UC Irvine. These clinics are specialized to support high quality trials focused on stem cell treatments for various diseases. The CIRM team will be bringing a new Alpha Clinics concept plan to its governing Board for approval in February.

Geoff Lomax, Senior Officer of Strategic Infrastructure at CIRM who oversees the CIRM Alpha Clinics, commented on the importance of City of Hope’s glioblastoma trial,

“Treating this form of brain cancer is one of the most vexing challenges in medicine. With the support and expertise of the CIRM Alpha Stem Cell Clinic, City of Hope is harnessing the power of patients’ immune cells to treat this deadly disease.”

Neil Littman, CIRM Director of Business Development and Strategic Infrastructure added,

“This study provides important proof-of-concept that CAR-T cells can be used to target hard-to-treat solid tumors and is precisely the type of trial the CIRM Alpha Stem Cell Clinic Network is designed to support.”

For more details on this study, watch the video below from City of Hope:

CIRM-funded stem cell trial for retinitis pigmentosa makes progress

A CIRM-funded clinical trial for retinitis pigmentosa (RP), a degenerative eye disease that causes blindness, recently reached its next milestone and announced the completion of its patient enrollment for a phase I/IIa study testing a stem cell derived therapy. This is a major step forward in determining whether this approach is both safe and effective at improving sight in RP patients.

retinitis pigmentosas_1RP is a genetically inherited disease that destroys the light-sensing photoreceptor cells at the back of the eye. Symptoms of the disease typically appear in childhood and often cause blindness by the age of 40. RP affects approximately 100,000 people in the US, and there are no effective treatments.

Stem cell treatment for RP

Regenerative medicine offers a promising strategy for treating RP by replacing the lost or damaged photoreceptors in the retina with healthy retinal cells derived from human stem cells.

CIRM is funding a clinical trial that’s testing a stem cell-based treatment for advanced RP. The trial is sponsored by a California-based company called jCyte, which was founded in 2012 by Dr. Henry Klassen and Dr. Jing Yang, both currently professors at UC Irvine.

The treatment involves injecting human retinal progenitor cells, which are derived from adult stem cells, into the damaged area of the retina at the back of the eye to hopefully improve vision. These progenitor cells could either replace the damaged photoreceptors in the eye, or could help rescue the remaining photoreceptors from being destroyed.

RP clinical trials makes progress

Earlier this year, jCyte reported that they had treated the first nine patients in their phase I/IIa safety trial and did not observe any negative side effects caused by the treatment. Today, they announced that they have finished the trial enrollment with a total of 28 patients. Four different doses of retinal progenitor cells were tested in this patient group to determine both safety and the optimal dose of cells. While the results of this trial won’t be available until next year, eight of the enrolled patients have already completed the one-year study and have shown promising safety results.

In a jCyte news release, Dr. Klassen explained:

Klassen“We have successfully completed four DSMB (Data Safety Monitoring Board) reviews. So far, trial participants have had no significant side effects, with good tolerance of the injected cells. We are quite gratified by the results.”

CIRM is also happy to hear these positive findings as proving that a stem cell treatment is safe in patients is essential for moving a clinical trial forward. Jonathan Thomas, Chairman of the CIRM Governing Board commented in a CIRM news release:

Jonathan Thomas

Jonathan Thomas

“We are really encouraged by the preliminary safety results of the jCyte trial. RP is a rare disease and an unmet medical need that could benefit from advances in stem cell-based treatments. The jCyte trial will hopefully pave the way for determining how stem cells can improve vision in RP patients, and ultimately other diseases of blindness.”

Next steps

As this trial moves forward, jCyte hopes to begin planning a phase IIb trial that will determine whether their stem cell-based therapy is effective at improving vision in advanced RP patients.

“I look forward to the next stage of development towards commercialization,” said jCyte CEO Paul Bresge. “We never lose sight of our singular goal: to ultimately deliver this much-needed therapy to patients.”

If all goes well, additional RP patients will be needed to participate in the second phase of the jCyte trial. Patients who are interested in learning more about this trial or enrolling in future trials, should visit the jCyte website.

If you want to learn more about how stem cells could potentially yield new treatments for diseases of blindness, watch our video “Eyeing Stem Cell Therapies for Vision Loss”.


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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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Bioengineered veins give hope to kidney disease patients on dialysis

As blood travels around your body, it helps your body get around. Blood is essential for delivering oxygen and nutrients to all the cells in your body and for removing waste products made by these cells. Your body contains approximately 1.5 gallons of blood, which translates to around 7% of your body weight. In order for all this blood to do its job, it needs to be constantly cleaned of waste and extra fluids.

Your kidneys are your blood’s best friend. They act as natural filters that remove those cellular waste products and extra fluid from the blood and pass them off to the bladder, where they are disposed of through urine. Kidneys have the important job of maintaining the proper balance of fluids, electrolytes and chemicals in the blood. They are also involved in other essential biological processes such as regulating blood pressure, making new blood cells, and maintaining healthy bones. It’s a big problem when your kidneys stop working. Without this built-in filtration system, toxic byproducts build up in your blood and cause a multitude of not fun symptoms.

Hemodialysis acts as an artificial kidney to filter the blood of kidney disease patients. (wikipedia)

Hemodialysis acts as an artificial kidney to filter the blood of kidney disease patients. (wikipedia)

More than half a million Americans suffering from kidney dysfunction or failure are being treated by hemodialysis. This process involves connecting a patient to a machine that acts as an artificial kidney. “Old blood” is pumped into the machine from a plastic tube, also known as a shunt, that’s inserted into the patient’s vein. The blood is then passed through a dialyzer which filters out the waste products and extra fluid and allows clean blood to pass through and be put back into the patient (see image).

While hemodialysis is successful at extending the lifespan of kidney disease patients, serious complications can arise from this treatment including uncontrolled changes in blood pressure, bone disease, and anemia. Another common problem occurs with the shunt that’s inserted into a patient’s vein. Shunts can cause infection, blood clots, and can also be rejected by a patient’s immune system. As a result, patients have to get new shunts implanted every year. This is not always feasible for older patients whose veins cannot hold up to this invasive procedure.

A tubular alternative for better hemodialysis

A North Carolina company called Humacyte is trying to improve current hemodialysis technology by engineering human acellular vessels (HAVs) (meaning that the vessels don’t have any cells) that can be transplanted into patients and develop into a human version of a shunt. Sounds complicated, but it’s not really!

First, scientists take muscle cells from human organ donors and coax these cells to grow into tube-like structures. During this process, the cells secrete a compound called cellulose – a component of the extracellular matrix – which forms a biological scaffold that maintains the structure of the cells.

Next, the scientists chemically wash away the muscle cells, leaving an intact scaffold with a hole the diameter of your pinky finger. These scaffolds are then placed under the skin of patients on dialysis. Once transplanted, a patient’s own stem cells migrate to the empty scaffold, set up shop and create a new vein with a wide enough hole that can be used for hemodialysis.

Humacyte’s Chief Medical Officer, Jeff Lawson, explained it an interview with KQED Science:

Jeff Lawson, Humacyte

Jeff Lawson, Humacyte

“This scaffold, once implanted, uniquely becomes repopulated with their own stem cells. That then turns back into something that looks like a vascular cell. And it now transitions over the period of a few months into something that’s indistinguishable from your own tissue. One of the holy grails in vascular surgery is to come up with a prosthetic artificial graft that has the same properties as the patient’s own blood vessels.”

The great news about this promising technology is that Humacyte is testing it in a Phase III clinical trial – the final stage before a drug or treatment is approved by the US Food and Drug Administration (FDA). In a Phase III trial, the treatment has already proven to be safe and shown some effectiveness (in a Phase II trial) and is now being tested in a larger group of patients to hopefully confirm these findings.

In July, CIRM invested $10 million in Humacyte’s Phase III trial in hopes that this technology will improve the lives and health of dialysis patients. Randy Mills, the President and CEO of CIRM, views kidney failure as an unmet medical need that could benefit from a stem cell related treatment:

“This approach has the potential to significantly improve our ability to care for people with kidney disease. Being able to reduce infections and clotting problems, and increase the consistency of care hemodialysis patients get, would meaningfully impact the quality of their lives.”

A patient’s story and CIRM’s efforts to fund clinical trials

Raymund Ramirez

Raymond Ramirez (KQED Science)

Yesterday, David Gorn from KQED Science published a nice piece about Humacyte’s stem cell derived technology and featured the story of a kidney failure patient, Raymond Ramirez. Raymond’s story is very emotional. He is a Vietnam war veteran that has experienced a gauntlet of maladies including bladder cancer and blindness in his right eye. On top of that, his kidneys aren’t functioning well and he is unable to continue his dialysis treatments because his veins aren’t holding up.

Raymond was the first patient to be treated in Humacyte’s Phase III trial. You can read more about his story here.

Gorn also highlighted CIRM’s recent efforts to fund promising stem cell projects that are further along in development and ready for clinical trials in patients. He ended with a quote from UC San Diego’s director of stem cell research, Larry Goldstein, on how important it is for our agency to continue funding stem cell clinical trials.

Larry Goldstein

Larry Goldstein

“Ten years ago I don’t think there were that many [stem cell] projects that were really ready for clinical trials. The field itself has developed projects that are at clinical stage. If the agency [CIRM] keeps pumping out these types of clinical results, California voters may soon see another ballot measure to keep it going.”

Full Steam Ahead: First Patient is Dosed in Expanded CIRM Spinal Cord Injury Trial

Today we bring you more good news about a CIRM-funded clinical trial for spinal cord injury that’s received a lot of attention lately in the news. Asterias Biotherapeutics has treated its first patient in an expanded patient population of spinal cord injury patients who suffer from cervical, or neck, injuries.

In late August, Asterias reported that they had passed the first hurdle in their Phase 1/2a trial and showed that their stem cell therapy is safe to use in patients with a more serious form of cervical spinal cord injuries.

Earlier this month, we received more exciting updates from Asterias – this time reporting that the their embryonic stem cell-based therapy, called AST-OPC1, appeared to benefit treated patients. Five patients with severe spinal cord injuries to their neck were dosed, or transplanted, with 10 million cells. These patients are classified as AIS-A on the ASIA impairment scale – meaning they have complete injuries in which the spinal cord tissue is severed and patients lose all feeling and use of their limbs below the injury site. Amazingly, after three months, all five of the AIS-A patients have seen improvements in their movement.

Today, Asterias announced that it has treated its first patient with an AIS-B grade cervical spinal cord injury with a dose of 10 million cells at the Sheperd Center in Atlanta. AIS-B patients have incomplete neck injuries, meaning that they still have some spinal cord tissue at the injury site, some feeling in their arms and legs, but no movement. This type of spinal cord injury is still severe, but these patients have a better chance at gaining back some of their function and movement after treatment.

In a press release by Asterias, Chief Medical Officer Dr. Edward Wirth said:

“We have been very encouraged by the first look at the early efficacy data, as well as the safety profile, for AST-OPC1 in AIS-A patients, and now look forward to also evaluating efficacy and safety in AIS-B patients. AIS-B patients also have severe spinal cord injuries, but compared to AIS-A patients they have more spared tissue in their spinal cords.  This may allow these patients to have a greater chance of meaningful functional improvement after being treated with AST-OPC1 cells.”

Dr. Donald Peck Leslie, who directs the Sheperd Center and is the lead investigator at the Atlanta clinical trial site, expressed his excitement about the trials’ progress.

“As someone who regularly treats patients who have sustained paralyzing spinal cord injuries, I am encouraged by the progress we’ve seen in evaluations of AST-OPC1 in people with AIS-A injuries, particularly the improvements in hand, finger and arm function. Now, I am looking forward to continuing the evaluation of this promising new treatment in AIS-B patients, as well.”

Asterias has plans to enroll a total of five to eight AIS-B patients who will receive a dose of 10 million cells. They will continue to monitor all patients in this trial (both AIS-A and B) and will conduct long-term follow up studies to make sure that the AST-OPC1 treatment remains safe.

We hope that the brave patients who have participated in the Asterias trial continue to show improvements following treatment. Inspiring stories like that of Kris Boesen, who was the first AIS-A patient to get 10 million cells in the Asterias trial and now has regained the use of his arms and hands (and regaining some sensation in his legs), are the reason why CIRM exists and why we are working so hard to fund promising clinical trials. If we can develop even one stem cell therapy that gives patients back their life, then our efforts here at CIRM will be worthwhile.

Kris Boesen, CIRM spinal cord injury clinical trial patient.

Kris Boesen, CIRM spinal cord injury clinical trial patient.


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Funding stem cell research targeting a rare and life-threatening disease in children

cystinosis

Photo courtesy Cystinosis Research Network

If you have never heard of cystinosis you should consider yourself fortunate. It’s a rare condition caused by an inherited genetic mutation. It hits early and it hits hard. Children with cystinosis are usually diagnosed before age 2 and are in end-stage kidney failure by the time they are 9. If that’s not bad enough they also experience damage to their eyes, liver, muscles, pancreas and brain.

The genetic mutation behind the condition results in an amino acid, cystine, accumulating at toxic levels in the body. There’s no cure. There is one approved treatment but it only delays progression of the disease, has some serious side effects of its own, and doesn’t prevent the need for a  kidney transplant.

Researchers at UC San Diego, led by Stephanie Cherqui, think they might have a better approach, one that could offer a single, life-long treatment for the problem. Yesterday the CIRM Board agreed and approved more than $5.2 million for Cherqui and her team to do the pre-clinical testing and work needed to get this potential treatment ready for a clinical trial.

Their goal is to take blood stem cells from people with cystinosis, genetically-modify them and return them to the patient, effectively delivering a healthy, functional gene to the body. The hope is that these genetically-modified blood stem cells will integrate with various body organs and not only replace diseased cells but also rescue them from the disease, making them healthy once again.

In a news release Randy Mills, CIRM’s President and CEO, said orphan diseases like cystinosis may not affect large numbers of people but are no less deserving of research in finding an effective therapy:

“Current treatments are expensive and limited. We want to push beyond and help find a life-long treatment, one that could prevent kidney failure and the need for kidney transplant. In this case, both the need and the science were compelling.”

The beauty of work like this is that, if successful, a one-time treatment could last a lifetime, eliminating or reducing kidney disease and the need for kidney transplantation. But it doesn’t stop there. The lessons learned through research like this might also apply to other inherited multi-organ degenerative disorders.

HOPE for patients with Duchenne Muscular Dystrophy-associated heart disease

It’s an exciting week for CIRM-funded clinical trials. Yesterday, we blogged about a young man named Kris Boesen who is responding positively to a stem cell therapy in a Phase 1/2a CIRM-funded clinical trial for spinal cord injury run by Asterias Biotherapeutics. Paralyzed from the chest down after a terrible car accident, Kris now has regained some use of his arms and hands following the stem cell transplant.

screen-shot-2016-09-08-at-9-18-46-amYesterday, Capricor Therapeutics also announced news about the progress of its CIRM-funded clinical trial that’s testing the safety and efficacy of a cardiac cell therapy called CAP-1002 for Duchenne Muscular Dystrophy-associated cardiomyopathy. Capricor has completed their Phase 1/2 trial enrollment of 25 patients. These patients are young boys (12 years of age or above) suffering from a build-up of scar tissue in their hearts due to DMD-associated cardiomyopathy. Reaching full enrollment is a key milestone for any clinical trial.

Duchenne Muscular Dystrophy (DMD) is an inherited disease that attacks muscle, causing muscle tissue to become weak and degenerate. The disease mainly appears in young boys between the ages of two and three. Patients with DMD often suffer from cardiomyopathy or weakened heart muscle caused by the thickening and hardening of the heart muscle and accumulation of scar tissue. DMD-associated cardiomyopathy is one of the leading causes of patient deaths.

President and CEO of Capricor, Dr. Linda Marban, believes there’s a potential for their CAP-1002 stem cell therapy to help DMD patients suffering from cardiomyopathy. She explained in a press release:

“In DMD, scar tissue progressively aggregates in the heart, leading to a deterioration of cardiac function for which treatment options are limited. We believe CAP-1002 is the only therapeutic candidate in development for the treatment of DMD that has been clinically shown to reduce scar tissue in the damaged heart.”

The Capricor trial was approved by the CIRM Board in March 2016 and since then Capricor has worked quickly to enroll patients in its HOPE-Duchenne trial (HOPE stands for Halt cardiomyopathy progression in Duchenne).

Dr. Marban commented on the trials recent progress:

Linda Marban, CEO of Capricor Therapeutics

Linda Marban, CEO of Capricor Therapeutics

“The rate of patient enrollment into HOPE-Duchenne far surpassed our expectations, signifying the need for therapeutic options as well as the desire of the DMD community to address the heart disease that is highly prevalent in this population. We look forward to announcing top-line six-month results from HOPE-Duchenne in the first quarter of next year, in which we will report on the safety as well as the potential efficacy of CAP-1002.”

Half of the enrolled patients will receive an infusion of the CAP-1002 cardiac cell therapy while the other half will receive regular care without the infusion. Capricor will monitor all these patients to make sure that the cell therapy is well tolerated and doesn’t cause any harm. It will also look for any positive signs that the therapy is benefiting patients using a series of tests that measure changes in scar tissue and heart function.

HOPE is high for this trial to succeed as there is currently no treatment that can successfully reduce the amount of cardiac scar tissue in patients suffering from DMD-associated cardiomyopathy. The Capricor trial is in its early stages, but check in with the Stem Cellar for an update on the safety and efficacy data from this trial in early 2017.


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