jCyte Shares Encouraging Update on Clinical Trial for Retinitis Pigmentosa

Stepping out of the darkness into light. That’s how patients are describing their experience after participating in a CIRM-funded clinical trial targeting a rare form of vision loss called retinitis pigmentosa (RP). jCyte, the company conducting the trial, announced 12 month results for its candidate stem cell-based treatment for RP.

RP is a genetic disorder that affects approximately 1 in 40,000 individuals and 1.5 million people globally. It causes the destruction of the light-sensing cells at the back of the eye called photoreceptors. Patients experience symptoms of vision loss starting in their teenage years and eventually become legally blind by middle age. While there is no cure for RP, there is hope that stem cell-based therapies could slow its progression in patients.

Photoreceptors look healthy in a normal retina (left). Cells are damaged in the retina of an RP patient (right). (Source National Eye Institute)

jCyte is one of the leaders in developing cell-based therapies for RP. The company, which was founded by UC Irvine scientists led by Dr. Henry Klassen, is testing a product called jCell, which is composed of pluripotent stem cell-derived progenitor cells that develop into photoreceptors. When transplanted into the back of the eye, they are believed to release growth factors that prevent further damage to the surviving cells in the retina. They also can integrate into the patient’s retina and develop into new photoreceptor cells to improve a patient’s vision.

Positive Results

At the Annual Ophthalmology Innovation Summit in November, jCyte announced results from its Phase 1/2a trial, which was a 12-month study testing two different doses of transplanted cells in 28 patients. The company reported a “favorable safety profile and indications of potential benefit” to patient vision.

The patients received a single injection of cells in their worst eye and their visual acuity (how well they can see) was then compared between the treated and untreated eye. Patients who received the lower dose of 0.5 million cells were able to see one extra letter on an eye chart with their treated eye compared to their untreated eye while patients that received the larger dose of 3 million cells were able to read 9 more letters. Importantly, none of the patients experienced any significant side effects from the treatment.

According to the company’s news release, “patient feedback was particularly encouraging. Many reported improved vision, including increased sensitivity to light, improved color discrimination and reading ability and better mobility. In addition, 22 of the 28 patients have been treated in their other eye as part of a follow-on extension study.”

One of these patients is Rosie Barrero. She spoke to us earlier this year about how the jCyte trial has not only improved her vision but has also given her hope. You can watch her video below.

Next Steps

These results suggest that the jCell therapy is safe (at least at the one year mark) to use in patients and that larger doses of jCell are more effective at improving vision in patients. jCyte CEO, Paul Bresge commented on the trial’s positive results:

Paul Bresge

“We are very encouraged by these results. Currently, there are no effective therapies to offer patients with RP. We are moving forward as quickly as possible to remedy that. The feedback we’ve received from trial participants has been remarkable. We look forward to moving through the regulatory process and bringing this easily-administered potential therapy to patients worldwide.”

Bresge and his company will be able to navigate jCell through the regulatory process more smoothly with the product’s recent Regenerative Medicine Advanced Therapy (RMAT) designation from the US Food and Drug Administration (FDA). The FDA grants RMAT to regenerative medicine therapies for serious diseases that have shown promise in early-stage clinical trials. The designation allows therapies to receive expedited review as they navigate their way towards commercialization.

jCyte is now evaluating the safety and efficacy of jCell in a Phase2b trial in a larger group of up to 85 patients. CIRM is also funding this trial and you can read more about it on our website.


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Positive update on Asterias’ SCiStar study for spinal cord injury at TMM 2017

This guest blog is reposted with permission from Signals Blog, published by the Center for Commercialization of Regenerative Medicine (CCRM) in Canada.

With the extensive exploitation of regenerative medicine through the marketing and selling of unapproved stem cell “therapies” online, it was refreshing to hear an update about clinical trials for a legitimate stem cell therapy at the Till & McCulloch Meetings (TMM) in Canada earlier this month.

Dr. Jane Lebkowski, of Asterias, speaking at TMM 2017

Dr. Jane Lebkowski, President of R&D and Chief Scientific Officer at Asterias Biotherapeutics Inc. shared updates from their SCiStar study. This California-based company is currently in an open-label, single-arm Phase 1/2a clinical trial for testing the safety and efficacy of treating several types of spinal cord injuries (SCI) with AST-OPC1s – a type of brain cell called an oligodendrocyte progenitor cell, which they derived from pluripotent stem cells. Earlier this year they reported promising safety results in their first two cohorts of patients and clearance to proceed into additional patients.

Asterias uses a cryopreserved human ESC (embryonic stem cell) line to derive their AST-OPC1s, which they report are a non-homogenous population containing mostly OPCs and some neural progenitor cells. Importantly, they do not observe evidence that any ESCs remain in their differentiated cultures.

Their clinical trial is operating off the heels of extensive nonclinical safety and efficacy studies in over 28 different animal studies in >3,000 rodents and pigs with a unilateral contusion SCI model, as well as data from the first ever human clinical trial with human ESC-derived products previously conducted by Geron.

In their last non-clinical animal model studies of cervical (neck) and thoracic (back) SCI, Asterias showed that as long as they inject cells within the first 30 days of injury they see a persistent reduction in cavity formation at the injury site. They also saw myelination (growth of a protective, insulating sheath around nerve extensions) of nerve cells when AST-OPC1s were injected into myelin-free Shiverer mice, and increased vascularization (blood vessel growth) of injured tissue that persists to nine months post-transplantation. They also have in vitro data to suggest that the injected cells can secrete neurotrophic factors. Importantly, they saw behavioural improvements in their animal models that include “increases in running speed, right forelimb stride length, right forelimb maximal longitudinal deviation, and right rear stride frequency.”

In her talk at TMM, Dr. Lebkowski gave some exciting details about the company’s most recent clinical study. They’ve been delivering their AST-OPC1s to 18-69 year-old patients with C4-C7 spinal cord injury at multiple doses: a low dose of about two million cells and medium at 10 million cells. They give a single injection of either two million, 10 million, or 20 million AST-OPC1s within 21 to 42 days of injury. They have results from patients in the first two cohorts so far, and reported that both two and 10 million cell doses appeared safe 12 months after administration.

Excitingly, patients who received 10 million cells showed signs of functional improvements (in their movement) that have so far persisted up to 12 months after the injection – an improvement of 12.3% on their motor test, equivalent to two full motor scores. This translates to increased arm and hand function and improved independence in activities of daily living at 12 months. Given that these patients were requiring over six hours of home care a day, even small improvements in motor function can have huge impact on their quality of life and independence.

The research community is still waiting to hear preliminary results from the third cohort of patients who received 20 million cells. Asterias is currently recruiting more patients, including those with incomplete spinal cord injury. These studies will be used to inform a larger, double-blind controlled clinical trial that will include more extensive tests of the functional and physiological effects of injecting AST-OPC1s.

This promising work has not been an easy road. It has taken over a decade of thorough and challenging research. The current work was made possible by a $14.3 million investment from the California Institute for Regenerative Medicine, and Dr. Lebkowski estimates that they have spent over $125 million U.S. for this trial. While Asterias covers non-routine medical costs for the patients who enroll, it will take time and more support from government institutions to further test this treatment and, if proven safe and effective, make it financially accessible to all eligible patients.

Returning to my first point about unapproved stem cell therapies, please engage in conversations about “hype and hope” of stem cell therapies with members of the general public, and encourage them to ask their family health team and a scientist before enrolling in any clinical trials advertised online. There are other ways you can keep our industry “honest” here. For more plain language resources on the current status of stem cell therapies, please see here and here.


Samantha Yammine

Samantha is a PhD Candidate studying neural stem cell biology in Dr. Derek van der Kooy’s lab at the University of Toronto. She is also an avid science communicator who uses social media to make science more accessible to everyone. For your daily dose of the fun and trendy side of science, find her online as @SamanthaZY on Twitter and @Science.Sam on Instagram. 

Hearts and brains are center stage at CIRM Patient Advocate event

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

ViaCyte treats first patients in PEC-Direct stem cell trial for type 1 diabetes

Today, ViaCyte shared an update on its latest clinical trial for type 1 diabetes (T1D). The company is based in San Diego and is developing two stem cell-based products that attempt to replace the pancreatic beta islet cells that are attacked by the immune system of patients with T1D.

Their first product, called VC-01 or PEC-Encap, is an implantable device containing embryonic stem cells that develop into pancreatic progenitor cells, which are precursors to the islet cells destroyed by T1D. The hope is that when this device is transplanted under a patient’s skin, the progenitor cells will develop into mature insulin-secreting cells that can properly regulate the glucose levels in a patient’s blood. Because the cells are encapsulated in a protective semi-permeable membrane, hormones and nutrients can pass in and out of the device, but the implanted cells are guarded against the patient’s immune system. VC-01 is currently being tested in a Phase 1 clinical trial that is funded CIRM.

ViaCyte now has a second product called VC-02, or PEC-Direct, that also transplants pancreatic progenitors but in a device that allows a patient’s blood vessels to make direct contact with the implanted cells. This “direct vascularization” approach is being tested in patients that are at high risk for severe complications associated with T1D including hypoglycemia unawareness – a condition where patients fail to recognize when their blood glucose level drops to dangerously low levels because the typical symptoms of hypoglycemia fail to appear.

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

In May, ViaCyte announced that the US Food and Drug Administration (FDA) approved their Investigational New Drug (IND) application for PEC-Direct, which gave the company the green light to proceed with a Phase 1 safety trial to test the treatment in patients. ViaCyte’s pre-IND work on PEC-Direct was supported in part by a late stage preclinical grant from CIRM.

Today, the ViaCyte announced in a press release that it has treated its first patients with PEC-Direct in a Phase 1/2 trial at the University of Alberta Hospital in Edmonton, Alberta and at the UCSD Alpha Stem Cell Clinic in San Diego, California.

“The first cohort of type 1 diabetes patients is receiving multiple small-format cell-filled devices called sentinels in order to evaluate safety and implant viability.  These sentinel units will be removed at specific time points and examined histologically to provide early insight into the progression of engraftment and maturation into pancreatic islet cells including insulin-producing beta cells.”

The news release also revealed plans for enrollment of a larger cohort of patients by the end of 2017.

“A second cohort of up to 40 patients is expected to begin enrolling later this year to evaluate both safety and efficacy.  The primary efficacy measurement in the trial will be the clinically relevant production of insulin, as measured by the insulin biomarker C-peptide, in a patient population that has little to no ability to produce endogenous insulin at the time of enrollment.  Other important endpoints will be evaluated including injectable insulin usage and the incidence of hypoglycemic events.  ViaCyte’s goal is to demonstrate early evidence of efficacy in the first half of 2018 and definitive efficacy 6 to 12 months later.”

President and CEO of ViaCyte, Dr. Paul Laikind, is hopeful that PEC-Direct will give patients with high-risk T1D a better treatment option than what is currently available.

ViaCyte’s President & CEO, Paul Laikind

“There are limited treatment options for patients with high-risk type 1 diabetes to manage life-threatening hypoglycemic episodes. We believe that the PEC-Direct product candidate has the potential to transform the lives of these patients and we are excited to move closer to that goal with the initiation of clinical evaluation announced today.  This also represents a step towards a broader application of the technology.  We remain fully committed to developing a functional cure for all patients with insulin-requiring diabetes.  To that end, we are hard at work on next-generation approaches as well, and expect the work with PEC-Direct to further advance our knowledge and drive progress.”


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Capricor reports positive results on CIRM-funded stem cell trial for Duchenne Muscular Dystrophy

Capricor Therapeutics, a Los Angeles-based company, published an update about its CIRM-funded clinical trial for patients with Duchenne muscular dystrophy (DMD), a devastating degenerative muscle disease that significantly reduces life expectancy.

The company reported positive results from their Phase I/II HOPE trial that’s testing the safety of their cardiosphere stem cell-based therapy called CAP-1002. The trial had 25 patients, 13 of which received the cells and 12 who received normal treatment. No serious adverse effects were observed suggesting that the treatment is “generally safe” thus far.

Patients given a single dose of CAP-1002 showed improvements “in certain measures of cardiac and upper limb function” after six months. They also experienced a reduction of cardiac scar tissue and a thickening of the heart’s left ventricle wall, which is typically thinned in DMD patients.

Capricor shared more details on their six-month trial results in a webcast this week, and you can read about them in this blog by Rare Disease Report.

Leading cause of death for DMD patients

DMD is a severe form of muscular dystrophy caused by a recessive genetic mutation in the dystrophin gene on the X chromosome. Consequently, men are much more likely to get the disease than women. Symptoms of DMD start with muscle weakness as early as four years of age, which then leads to deterioration of both skeletal and heart muscle. Heart disease is the leading cause of death in DMD patients – a fact that Capricor hopes to change with its clinical trial.

Capricor’s CEO, Dr. Linda Marbán, commented in a press release that the trial’s results support the findings of other researchers.

“These initial positive clinical results build upon a large body of preclinical data which illustrate CAP-1002’s potential to broadly improve the condition of those afflicted by DMD, as they show that cardiosphere-derived cells exert salutary effects on cardiac and skeletal muscle.”

Also quoted in the press release was Pat Furlong, DMD patient advocate and CEO of Parent Project Muscular Dystrophy.

Pat Furlong

“I’m excited to see these data, especially given the advanced nature of the patients in the HOPE trial. It is also gratifying to see the field of cell therapy making progress after more than two decades in development. It is our hope that CAP-1002 will have broad potential to improve the lives of patients with Duchenne muscular dystrophy.”

Pat recently spoke at the 2nd Annual CIRM Alpha Stem Cell Clinics meeting about her heartbreaking experience of losing two sons to DMD, both at a very young age. You can watch her speech below. We also featured her story and her inspiring efforts to promote DMD awareness in our 2016 Annual Report.

What to HOPE for next?

The trial is a year-long study and Capricor will report 12-month results at the end of 2017. In the meantime, Dr. Marbán and her team have plans to talk with the US Food and Drug Administration (FDA) about the regulatory options for getting CAP-1002 approved and on the market for DMD patients. She explained,

Linda Marban, CEO of Capricor Therapeutics

“We have submitted an FDA meeting request to discuss these results as well as next steps in our development of CAP-1002 for Duchenne muscular dystrophy, which includes our plan to begin a clinical trial of intravenously-administered CAP-1002 in the latter half of this year. We believe the interim HOPE results may enable us to pursue one of the FDA’s Expedited Programs for Serious Conditions, and we will apply for either or both of the Breakthrough Therapy and Regenerative Medicine Advanced Therapy (RMAT) designations for CAP-1002.”


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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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