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. 

Three stories give us a glimpse of the real possibilities for stem cell therapies

Today we’re featuring a guest blog by Lisa Willemse about the Till and McCulloch Stem Cell Meeting in Canada. Enjoy!

Stem cell treatments should be incredibly easy. Or rather, that’s what some clinics or products would have you believe. Because, on the surface, a one-stop-shop for injectable cells to cure just about any condition or topical creams to peel away the scourge of time are very easy.

Attend one stem cell research conference and you’ll be convinced that it’s much more complicated. It’s a sea of reagents and transcription factors and unknown cause-and-effect. Many researchers will spend their entire career working on just one unknown and their caution and concern when it comes to the notion of a cure is justifiable.

Whistler (Courtesy of Lisa Willemse)

Whistler (Courtesy of Lisa Willemse)

Which makes it all the more impactful when you attend a research conference and hear three talks, back-to-back, that demonstrate that we’re ticking off some of those unknowns and getting much closer to real – not sham – therapies. Therapies with a sound scientific basis that are well planned and done with patient safety (not sales) in mind. Last week’s Till and McCulloch Meetings, held in Whistler, British Columbia gave us a sense of what is possible for three conditions: macular degeneration (vision), septic shock and a rare neurologic disease (Stiff Person Syndrome). Other blogs have covered  different aspects of this meeting here and here.

Vision Repair – Age-related Macular Degeneration (AMD)

As the world’s first clinical trial to use induced pluripotent stem cells launched amid sweeping regulatory changes in Japan, Dr. Masayo Takahashi’s treatment protocol for AMD has received no small amount of scrutiny. After a brief hiatus, the trial was back on track earlier this year and Takahashi’s presentation at this meeting was highly anticipated.

Dr. Masayo Takahashi

Dr. Masayo Takahashi

It did not disappoint. Takahashi spent the better part of her time outlining the steps taken to reach the point where the clinical trial was possible, including multiple studies in mice and further refinement of the treatment to ensure it would be stable in humans even with genetic changes over time. Given that one of the reasons the trial was put on hold was due to genetic mutations found in the cells prepared for the second potential human transplant, Takahashi’s careful work in ensuring the product was safe bodes well for the future of this trial.

The first patient was treated in 2014, a 78-year-old woman with wet AMD in the right eye, and although only minimal visual improvement was documented, the patient anonymously told the Japan Times, “I’m glad I received the treatment. I feel my eyesight has brightened and widened.”

Takahashi also alluded to some of the other challenges she’d had to overcome to make this trial a reality, including would-be critics who told her that the nervous system and the retina were too complicated to regenerate. Takahashi’s response? “You don’t know stem cells [and] you don’t understand the needs of the patient.”

While it was unclear when the next patient will receive treatment, Takahashi did say that three new applications for clinical trials using her refined protocols have been submitted for approval.

Septic shock  

Septic shock is not a condition that gets a lot of attention, most likely because it’s not a primary illness, but a secondary one; a drastic and often fatal immune response that severely reduces blood pressure and cell metabolism. It accounts for 20% of all intensive care unit (ICU) admissions and is the most common cause of non-coronary mortality in the ICU. For those who survive septic shock, there are significant and long-term health consequences.

Over 100 clinical trials have attempted to improve outcomes for patients with septic shock, but not one has been successfully translated into the clinical setting. Supportive care remains the mainstay of therapy.

Dr. Lauralyn McIntyre

Dr. Lauralyn McIntyre

This was the sober backdrop painted by critical care physician, Dr. Lauralyn McIntyre as she began her talk on the world’s first stem cell clinical trial for septic shock she is co-leading in Ottawa with Dr. Duncan Stewart.

Like Takahashi, McIntyre spent a good deal of time explaining the rationale and research that underpin the trial, which takes advantage of the immune-modulating properties of mesenchymal stromal cells (also called mesenchymal stem cells or MSCs) to suppress and reverse the effects of septic shock. This work includes reviews of more than 50 studies that looked at the effects of MSCs in both human trials and animal studies.

McIntyre also discussed research she did with mice in 2010 as a proof-of-concept, where the MSC therapy was delayed for six days. This delay is important as it better simulates the time frame in which most patients arrive in the hospital. As McIntryre pointed out, if the therapy only worked when given within hours of disease development, what good would it be for patients who come in on day six?

Fortunately, the therapy worked in the mice, even after a delayed timeframe, providing a green light for safety testing in humans. The small first human trial is currently underway for nine patients (with a control arm of 21) with results not yet published – although one of the patients shared his experience earlier this year. McIntyre relayed that the early data is very encouraging – enough that the team is moving ahead with a Phase 2 randomized trial in 10 centres across Canada in 2017.

Stiff Person Syndrome

Tina Ceroni’s story is much more personal. She is only the second person in the world to have received an experimental stem cell treatment for Stiff Person Syndrome, a rare neurologic condition that causes uncontrolled and sustained contractions of the arm, leg or other muscles. Often misdiagnosed initially as Multiple Sclerosis or anxiety/depression, SPS is also an autoimmune disease for which the cause is unknown.

Tina Ceroni

Tina Ceroni (The Ottawa Hospital)

I’ve written about Tina’s story before – about how she was hospitalized 47 times in one year and how a chance meeting with another SPS patient propelled Ceroni on a journey that included an intensive stem cell therapy under the guidance of Dr. Harry Atkins at the Ottawa Hospital, in which her blood stem cells were harvested from her bone marrow and used to repopulate her system after her immune system was wiped clean with chemotherapy.

Now a stem cell advocate, Ceroni’s story keeps getting better – not merely in how powerfully and passionately she tells it, but in the continued good health she enjoys after her treatment and in her efforts to share it more broadly.

Most importantly, she drives home a key message:

“My story underscores the importance of clinical trials…. My experience will help to change the future for others. I am living proof that a clinical trial for stem cell therapy can have a life-changing outcome.”

“Often hope is the only medicine we have.”

It’s important that patients like Ceroni continue share their story, not just with the research community to give a human face to the work they do, but to show that solid research is making an impact, one that can be measured in lives saved.


Lisa Willemse

Lisa Willemse

This article is published simultaneously, with permission by the author, Lisa Willemse, on the Ontario Institute for Regenerative Medicine (OIRM) Expression blog.