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.

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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.

First spinal cord injury trial patient gets maximum stem cell dose

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Kris Boesen, CIRM spinal cord injury clinical trial patient.

There comes a pivotal point in every experiment where you say “ok, now we are going to see if this really works.” We may be at that point in the clinical trial we are funding to see if stem cells can help people with spinal cord injuries.

Today Asterias Biotherapeutics announced they have given the first patient in the clinical trial the highest dose of 20 million cells. The therapy was administered at Santa Clara Valley Medical Center (SCVMC) in San Jose, California where Jake Javier – a young man who was treated at an earlier stage of the trial – was treated. You can read Jake’s story here.

The goal of the trial is to test the safety of transplanting three escalating doses of AST-OPC1 cells. These are a form of cell called oligodendrocyte progenitors, which are capable of becoming several different kinds of nerve cells, some of which play a supporting role and help protect nerve cells in the central nervous system – the area damaged in spinal cord injury.

In a news release, Dr. Edward Wirth, Asterias’ Chief Medical Officer, says this could be a crucial phase in the trial:

“We have been very encouraged by the early clinical efficacy and safety data for AST-OPC1, and we now look forward to evaluating the 20 million cell dose in complete cervical spinal cord injury patients. Based on extensive pre-clinical research, this is in the dosing range where we would expect to see optimal clinical improvement in these patients.”

To be eligible, individuals have to have experienced a severe neck injury in the last 30 days, one that has left them with no sensation or movement below the level of their injury, and that means they have typically lost all lower limb function and most hand and arm function.

In the first phase individuals were given 2 million cells. This was primarily to make sure that this approach was safe and wouldn’t cause any problems for the patients. The second phase boosted that dose to ten million cells. That was thought to be about half the therapeutic dose but it seemed to help all those enrolled. By 90 days after the transplant all five patients treated with ten million cells had shown some level of recovery of at least one motor level, meaning they had regained some use of their arms and/or hands on at least one side of their body. Two of the patients experienced an improvement of two motor levels. Perhaps the most impressive was Kris Boesen, who regained movement and strength in both his arms and hands. He says he is even experiencing some movement in his legs.

All this is, of course, tremendously encouraging, but we also have to sound a note of caution. Sometimes individuals experience spontaneous recovery after an accident like this. The fact that all five patients in the 10 million cell group did well suggests that this may be more than just a coincidence. That’s why this next group, the 20 million cell cohort, is so important.

As Steve McKenna, Chief of the Trauma Center at SCVMC, says; if we are truly going to see an improvement in people’s condition because of the stem cell transplant, this is when we would expect to see it:

“The early efficacy results presented in September from the 10 million cell AIS-A cohort were quite encouraging, and we’re looking forward to seeing if those meaningful functional improvements are maintained through six months and beyond. We are also looking forward to seeing the results in patients from the higher 20 million cell AST-OPC1 dose, as well as results in the first AIS-B patients.”

For more information about the Asterias clinical trial, including locations and eligibility requirements, go here: www.clinicaltrials.gov, using Identifier NCT02302157, and at the SCiStar Study Website (www.SCiStar-study.com).

We can never talk about this clinical trial without paying tribute to a tremendous patient advocate and a great champion of stem cell research, Roman Reed. He’s the driving force behind the Roman Reed Spinal Cord Injury Research Act  which helped fund the pioneering research of Dr. Hans Keirstead that laid the groundwork for this clinical trial.

 

 

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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Asterias’ stem cell clinical trial shows encouraging results for spinal cord injury patients

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Jake Javier; Asterias spinal cord injury clinical trial participant

When researchers are carrying out a clinical trial they have two goals: first, show that it is safe (the old “do no harm” maxim) and second, show it works. One without the other doesn’t do anyone any good in the long run.

A few weeks ago Asterias Biotherapeutics showed that their CIRM-funded stem cell therapy for spinal cord injuries appeared to be safe. Now their data suggests it’s working. And that is a pretty exciting combination.

Asterias announced the news at the annual scientific meeting of the International Spinal Cord Society in Vienna, Austria. These results cover five people who got a transplant of 10 million cells. While the language is muted, the implications are very encouraging:

“While early in the study, with only 4 of the 5 patients in the cohort having reached 90 days after dosing, all patients have shown at least one motor level of improvement so far and the efficacy target of 2 of 5 patients in the cohort achieving two motor levels of improvement on at least one side of their body has already been achieved.”

What does that mean for the people treated? A lot. Remember these are people who qualified for this clinical trial because of an injury that left them pretty much paralyzed from the chest down. Seeing an improvement of two motor levels means they are regaining some use of their arms, hands and fingers, and that means they are regaining the ability to do things like feeding, dressing and bathing themselves. In effect, it is not only improving their quality of life but it is also giving them a chance to lead an independent life.

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Kris Boesen, Asterias clinical trial participant

One of those patients is Kris Boesen who regained the use of his arms and hands after becoming the first patient in this trial to get a transplant of 10 million cells. We blogged about Kris here

Asterias says of the 5 patients who got 10 million cells, 4 are now 90 days out from their transplant. Of those:

  • All four have improved one motor level on at least one side
  • 2 patients have improved two motor levels on one side
  • One has improved two motor levels on both sides

What’s also encouraging is that none of the people treated experienced any serious side effects or adverse events from the transplant or the temporary use of immunosuppressive drugs.

Steve Cartt, CEO of Asterias, was understandably happy with the news and that it allows them to move to the next phase:

“We are quite encouraged by this first look at efficacy results and look forward to reporting six-month efficacy data as planned in January 2017.  We have also just recently been cleared to begin enrolling a new cohort and administering to these new patients a much higher dose of 20 million cells.  We look forward to begin evaluating efficacy results in this higher-dose cohort in the coming months as well.”

People with spinal cord injuries can regain some function spontaneously so no one is yet leaping to the conclusion that all the progress in this trial is due to the stem cells. But to see all of the patients in the 10 million stem cell group do well is at the very least a positive sign. Now the hope is that these folks will continue to do well, and that the next group of people who get a 20 million cell transplant will also see improvements.

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Roman Reed, spinal cord injury patient advocate

While the team at Asterias were being cautiously optimistic, Roman Reed, whose foundation helped fund the early research that led to this clinical trial, was much less subdued in his response. He was positively giddy:

“If one patient only improves out of the five, it can be an outlier, but with everyone improving out of the five this is legit, this is real. Cures are happening!”

 

Young man with spinal cord injury regains use of hands and arms after stem cell therapy

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Kris Boesen – Photo courtesy USC

Hope is such a fragile thing. We cling to it in bad times. It offers us a sense that we can bear whatever hardships we are facing today, and that tomorrow will be better.

Kris Boesen knows all about holding on to hope during bad times. On March 6th of this year he was left paralyzed from the neck down after a car accident. Kris and his parents were warned the damage might be permanent.

Kris says at that point, life was pretty bleak:

“I couldn’t drink, couldn’t feed myself, couldn’t text or pretty much do anything, I was basically just existing. I wasn’t living my life, I was existing.”

For Kris and his family hope came in the form of a stem cell clinical trial, run by Asterias Biotherapeutics and funded by CIRM. The Asterias team had already enrolled three patients in the trial, each of whom had 2 million cells transplanted into their necks, primarily to test for safety. In early April Kris became the first patient in the trial to get a transplant of 10 million stem cells.

Within two weeks he began to show signs of improvement, regaining movement and strength in his arms and hands:

“Now I have grip strength and do things like open a bottle of soda and feed myself. Whereas before I was relying on my parents, now after the stem cell therapy I am able to live my life.”

The therapy involves human embryonic stem cells that have been differentiated, or converted, into cells called oligodendrocyte progenitors. These are capable of becoming the kind of cells which help protect nerve cells in the central nervous system, the area damaged in spinal cord injury.

The surgery was performed by Keck Medicine of USC’s Dr. Charles Liu. In a news release about the procedure, he says improvements of the kind Kris has experienced can make a huge difference in someone’s life:

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Dr. Charles Liu, Keck School of Medicine: Photo courtesy USC

“As of 90 days post-treatment, Kris has gained significant improvement in his motor function, up to two spinal cord levels. In Kris’ case, two spinal cord levels means the difference between using your hands to brush your teeth, operate a computer or do other things you wouldn’t otherwise be able to do, so having this level of functional independence cannot be overstated.”

We blogged about this work as recently as last week, when Asterias announced that the trial had passed two important safety hurdles.  But Kris’ story is the first to suggest this treatment might actually be working.

Randy Mills, CIRM’s President & CEO, says:

 “With each patient treated in this clinical trial we learn.  We gain more experience, all of which helps us put into better context the significance of this type of event for all people afflicted with debilitating spinal cord injuries. But let us not lose sight of the individual here.  While each participant in a clinical trial is part of the group, for them success is binary.  They either improve or they do not.  Kris bravely and selflessly volunteered for this clinical trial so that others may benefit from what we learn.  So it is fitting that today we celebrate Kris’ improvements and stop to thank all those participating in clinical trials for their selfless efforts.”

For patient advocates like Roman Reed, this was a moment to celebrate. Roman has been championing stem cell research for years and through his Roman Reed Foundation helped lay the groundwork for the research that led to this clinical trial:

This is clear affirmative affirmation that we are making Medical History!  We were able to give a paralyzed quadriplegic patient back the use of his hands! With only half a clinical dosage. Now this person may hold and grasp his loved ones hands in his own hands because of the actions of our last two decades for medical research for paralysis CURE! CARPE DIEM!”

It’s not unheard of for people with the kind of injury Kris had to make a partial recovery, to regain some use of their arms and hands, so it’s impossible to know right now if the stem cell transplant was the deciding factor.

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Kris at home: photo courtesy USC

Kris’ dad, Rodney, says he doesn’t care how it happened, he’s just delighted it did:

“He’s going to have a life, even if (the progress) stops just this second, and this is what he has, he’s going to have a better life than he would have definitely had before, because there are so many things that this opens up the world for him, he’s going to be able to use his hands.”


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Clearing the first hurdle: spinal cord injury trial passes safety review

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Jake Javier, participant in Asterias clinica trial

Starting a clinical trial is like taking a step into the unknown. It’s moving a potential therapy out of the lab and testing it in people. To reach this point the researchers have done a lot of work trying to ensure the therapy is safe. But that work was done in the lab, and on mice or other animals. Now it’s time to see what happens when you try it in the real world.

It can be quite nerve wracking for everyone involved: both the researchers, because years of hard work are at stake, and the patients, because they’re getting something that has never been tested in humans before; something that could, potentially, change their lives.

Today we got some good news about one clinical trial we are funding, the Asterias Biotherapeutics spinal cord injury trial. Asterias announced that its Data Monitoring Committee (DMC) has reviewed the safety data from the first two groups of patients treated and found no problems or bad side effects.

That’s an important first step in any clinical trial because it shows that, at the very least, the therapy is not going to make the patient’s condition any worse.

The big question now, is will it make their condition better? That’s something we’ll come back to at a later date when we have a better idea how the people treated in the trial are doing. But for now let’s take a deeper dive into the safety data.

Asterias – by the numbers

This current trial is a Phase 1/2a trial. The people enrolled have all experienced injuries in the C5-C7 vertebrae – that’s high up in the neck – and have essentially lost all feeling and movement below the injury site. All are treated between two weeks and one month after the injury was sustained.

The therapy involves transplants of Asterias’ AST-OPC1 cells which were made from human embryonic stem cells. The AST-OPC1 cells have been turned into oligodendrocyte progenitors, which are capable of becoming the kind of cells which help protect nerve cells in the central nervous system, the area damaged in spinal cord injury.

The first group of three patients in the Asterias trial was given 2 million cells. The second group of five patients received 10 million cells. The DMC said the safety data from those patients looked fine, that there were no signs of problems.

As Dr. Edward Wirth, the Chief Medical Officer at Asterias, said in a news release, this means the company can plan for its next phase:

“The positive safety data in the previous phase 1 study and in the ongoing phase 1/2a study gives us the confidence to now proceed to administration of 20 million cells, which based on our significant pre-clinical research is likely well within the dosing range where we would expect to see clinically meaningful improvement in these patients.”

Asterias is now looking to enroll 5-8 patients for this 20 million cell phase.

jake and family

For people like Jake Javier this news is not about numbers or data, it’s personal. Earlier this summer Jake broke his neck at a pool party, celebrating graduating from high school. It left him paralyzed from the chest down with extremely limited use of his arms and hands. On July 7th Jake was enrolled in the Asterias trial, and had ten million cells transplanted into his neck.

It could be months, even as much as one year, before we know if those cells are having any beneficial effect on Jake. But at least for now we know they don’t seem to be having any negative effects.

“First do no harm” is the cardinal rule that all budding physicians are taught. This trial seems to be meeting that benchmark. Our hope now is that it will do a lot more, and truly make a difference in the lives of people like Jake.

As Randy Mills, CIRM’s President and CEO, said in a news release:

“I recently met with Jake and heard first-hand what he and his family are going through in the aftermath of his injury. But I also saw a young man with remarkable courage and determination. It is because of Jake, and the others who volunteer to take part in clinical trials, that progress is possible. They are true heroes.”


* On a side note, Roman Reed, a great champion of stem cell research and a patient advocate extraordinaire, helped make much of this story happen. He helped Jake enroll in the Asterias trial ,and the research that led to this therapy was pioneered by Dr. Hans Keirstead who was funded by the Roman Reed Spinal Cord Injury Research Act.

 

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Stem cell stories that caught our eye: turning on T cells; fixing our brains; progress and trends in stem cells; and one young man’s journey to recover from a devastating injury

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A healthy T cell

Here are some stem cell stories that caught our eye this past week. Some are groundbreaking science, others are of personal interest to us, and still others are just fun.

Directing the creation of T cells. To paraphrase the GOP Presidential nominee, any sane person LOVES, LOVES LOVES their T cells, in a HUGE way, so HUGE. They scamper around the body getting rid of viruses and the tiny cancers we all have in us all the time. A CIRM-funded team at CalTech has worked out the steps our genetic machinery must take to make more of them, a first step in letting physicians turn up the action of our immune systems.

We have known for some time the identity of the genetic switch that is the last, critical step in turning blood stem cells into T cells, but nothing in our body is as simple as a single on-off event. The Caltech team isolated four genetic factors in the path leading to that main switch and, somewhat unsuspected, they found out those four steps had to be activated sequentially, not all at the same time. They discovered the path by engineering mouse cells so that the main T cell switch, Bcl11b, glows under a microscope when it is turned on.

“We identify the contributions of four regulators of Bcl11b, which are all needed for its activation but carry out surprisingly different functions in enabling the gene to be turned on,” said Ellen Rothenberg, the senior author in a university press release picked up by Innovations Report. “It’s interesting–the gene still needs the full quorum of transcription factors, but we now find that it also needs them to work in the right order.”

Video primer on stem cells in the brain.  In conjunction with an article in its August issue, Scientific American posted a video from the Brain Forum in Switzerland of Elena Cattaneo of the University of Milan explaining the basics of adult versus pluripotent stem cells, and in particular how we are thinking about using them to repair diseases in the brain.

The 20-minute talk gives a brief review of pioneers who “stood alone in unmarked territory.” She asks how can stem cells be so powerful; and answers by saying they have lots of secrets and those secrets are what stem cell scientist like her are working to unravel.  She notes stem cells have never seen a brain, but if you show them a few factors they can become specialized nerves. After discussing collaborations in Europe to grow replacement dopamine neurons for Parkinson’s disease, she went on to describe her own effort to do the same thing in Huntington’s disease, but in this case create the striatal nerves lost in that disease.

The video closes with a discussion of how basic stem cell research can answer evolutionary questions, in particular how genetic changes allowed higher organisms to develop more complex nervous systems.

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CIRM Science Officers Kelly Shepard and Kent Fitzgerald

A stem cell review that hits close to home.  IEEE Pulse, a publication for scientists who mix engineering and medicine and biology, had one of their reporters interview two of our colleagues on CIRM’s science team. They asked senior science officers Kelly Shepard and Kent Fitzgerald to reflect on how the stem cell field has progressed based on their experience working to attract top researchers to apply for our grants and watching our panel of outside reviewers select the top 20 to 30 percent of each set of applicants.

One of the biggest changes has been a move from animal stem cell models to work with human stem cells, and because of CIRM’s dedicated and sustained funding through the voter initiative Proposition 71, California scientists have led the way in this change. Kelly described examples of how mouse and human systems are different and having data on human cells has been critical to moving toward therapies.

Kelly and Kent address several technology trends. They note how quickly stem cell scientists have wrapped their arms around the new trendy gene editing technology CRISPR and discuss ways it is being used in the field. They also discuss the important role of our recently developed ability to perform single cell analysis and other technologies like using vessels called exosomes that carry some of the same factors as stem cells without having to go through all the issues around transplanting whole cells.

“We’re really looking to move things from discovery to the clinic. CIRM has laid the foundation by establishing a good understanding of mechanistic biology and how stem cells work and is now taking the knowledge and applying it for the benefit of patients,” Kent said toward the end of the interview.

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Jake Javier and his family

Jake’s story: one young man’s journey to and through a stem cell transplant; As a former TV writer and producer I tend to be quite critical about the way TV news typically covers medical stories. But a recent story on KTVU, the Fox News affiliate here in the San Francisco Bay Area, showed how these stories can be done in a way that balances hope, and accuracy.

Reporter Julie Haener followed the story of Jake Javier – we have blogged about Jake before – a young man who broke his spine and was then given a stem cell transplant as part of the Asterias Biotherapeutics clinical trial that CIRM is funding.

It’s a touching story that highlights the difficulty treating these injuries, but also the hope that stem cell therapies holds out for people like Jake, and of course for his family too.

If you want to see how a TV story can be done well, this is a great example.

Stem cell transplant offers Jake a glimpse of hope

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Jake Javier surrounded by friends; Photo courtesy Julie Haener KTVU

On Thursday, July 7th, Jake Javier became the latest member of a very select group. Jake underwent a stem cell transplant for a spinal cord injury at Santa Clara Valley Medical Center here in the San Francisco Bay Area.

The therapy is part of the CIRM-funded clinical trial run by Asterias Biotherapeutics. For Asterias it meant it had hit a significant milestone (more on that later). But for Jake, it was something far more important. It was the start of a whole new phase in his life.

Jake seriously injured his spinal cord in a freak accident after diving into a swimming pool just one day before he was due to graduate from San Ramon Valley high school. Thanks, in part, to the efforts of the tireless patient advocate and stem cell champion Roman Reed, Jake was able to enroll in the Asterias trial.

astopc1The goal of the trial is to test the safety of transplanting three escalating doses of AST-OPC1 cells. These are a form of cell called oligodendrocyte progenitors, which are capable of becoming several different kinds of brain cells, some of which play a supporting role and help protect nerve cells in the central nervous system – the area damaged in spinal cord injury.

To be eligible, individuals have to have experienced a severe neck injury in the last 30 days, one that has left them with no sensation or movement below the level of their injury, and that means they have typically lost all lower limb function and most hand and arm function.

The first group of three patients was completed in August of last year. This group was primarily to test for safety, to make sure this approach was not going to cause any harm to patients. That’s why the individuals enrolled were given the relatively small dose of 2 million cells. So far none of the patients have experienced any serious side effects, and some have even shown some small improvements.

In contrast, the group Jake is in were given 10 million cells each. Jake was the fifth person treated in this group. That means Asterias can now start assessing the safety data from this group and, if there are no problems, can plan on enrolling people for group 3 in about two months. That group of patients will get 20 million cells.

It’s these two groups, Jakes and group 3, that are getting enough cells that it’s hoped they will see some therapeutic benefits.

In a news release, Steve Cartt, President and CEO of Asterias, said they are encouraged by the progress of the trial so far:

“Successful completion of enrollment and dosing of our first efficacy cohort receiving 10 million cells in our ongoing Phase 1/2a clinical study represents a critically important milestone in our AST-OPC1 clinical program for patients with complete cervical spinal cord injuries. In addition, while it is still very early in the development process and the patient numbers are quite small, we are encouraged by the upper extremity motor function improvements we have observed so far in patients previously enrolled and dosed in the very low dose two million cell cohort that had been designed purely to evaluate safety.”

 

jake and familyJake and his family are well aware that this treatment is not going to be a cure, that he won’t suddenly get up and walk again. But it could help him in other, important ways, such as possibly getting back some ability to move his hands.

The latest news is that Jake is doing well, that he experienced some minor problems after the surgery but is bouncing back and is in good spirits.

Jake’s mother Isabelle said this has been an overwhelming experience for the family, but they are getting through it thanks to the love and support of everyone who hears Jake’s story. She told CIRM:

 “We are all beyond thrilled to have an opportunity of this magnitude. Just the thought of Jake potentially getting the use of his hands back gives him massive hope. Jake has a strong desire to recover to the highest possible level. He is focused and dedicated to this process. You have done well to choose him for your research. He will make you proud.”

He already has.

Jake and Brady gear

New England Patriots star quarterback Tom Brady signed a ball and jersey for Jake after hearing about the accident


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More Good News From CIRM-Funded Spinal Cord Injury Trial

It’s been less than a year since we last reported on the CIRM-funded Asterias Biotherapeutics trial for spinal cord injury (SCI), and we already have more – still preliminary – but good news to share. The company recently released encouraging long-term follow-up results from their original Phase 1 clinical trial that suggest their stem cell treatment is safe and possibly effective for treating SCI occurring in the back region.

astopc1Back in August 2015, the California-based company reported positive results for the second phase of the clinical trial, the ongoing Phase 1/2a trial, that is testing their AST-OPC1 brain progenitor cell treatment in patients with cervical or neck spinal cord injury. They treated three patients with a low dose of two million AST-OPC1 cells and observed no serious side effects after two months. You can read more about these initial results in our blog.

Asterias plans to expand their Phase 1/2a trial by enrolling more patients and administering higher numbers of cells in hopes that a higher dose might impact or improve motor function in SCI patients. But with any cell transplantation therapy, there is always concerns about whether it’s safe and whether it could cause any long-term consequences in patients.

Good news to those who wait

A news release by Asterias yesterday, puts some of these fears to rest. They report new long-term data on their original Phase 1 trial, which was carried out by Geron, that treated patients with thoracic or back SCI. In this trial, five patients were treated with two million AST-OPC1 cells between 7 and 14 days post injury. The patients were given immunosuppressive drugs for two months so they wouldn’t reject the cell transplant and then were monitored over the next 4-5 years.

During this time, none of the patients showed any signs of transplant rejection, and MRI scans revealed that four out of the five patients showed less cavitation in their spinal cords, a destructive process that occurs after severe spinal cord injury.

Thus it seems that AST-OPC1 does not pose any serious safety issues for SCI patients, at least at the five-year mark. Chief Medical Officer Dr. Edward Wirth explained:

Edward Wirth, CMO at Asterias

Edward Wirth, CMO at Asterias

“This new long term follow-up data continues to support the general safety of AST-OPC1 and indicate minimal risk of the transplanted cells having unintended effects. In detailed immune response monitoring of patients, the results are consistent with long-term cell engraftment, immune system tolerability, and an absence of adverse effects.  In short, AST-OPC1 does not appear to present any immunological or other long-term safety issues when administered to patients suffering from spinal cord injuries.”

These positive long-term results are perfectly timed for Asteria’s expansion of their Phase 1/2a trial where they aim to test doses of AST-OPC1 that they believe would improve motor function in SCI patients. Asterias CEO Steve Cartt commented:

Steve Cartt, CEO of Asterias Biotherapeutics

Steve Cartt, CEO of Asterias

“These new follow-up results are very encouraging and provide important further support for expansion of the ongoing Phase 1/2a clinical study in patients with complete cervical spinal cord injuries announced just last week. We are continuing to enroll patients in the second dose cohort of the current Phase 1/2a trial.  Patients in this cohort are receiving a significantly higher dose of 10 million cells, which we believe corresponds to the doses that showed efficacy in animal studies.”

But that’s not all folks!

Dr. Edward Wirth, Asterias Biotherapeutics

Dr. Edward Wirth from Asterias Biotherapeutics at the CIRM Alpha Clinics Meeting in May

CIRM got the inside scoop on the next steps of this Phase 1/2a trial last week at a CIRM Alpha Stem Cell Clinics Meeting held at UC Irvine. Dr. Edward Wirth was the guest speaker, and during lunch, he explained how their recent successes in both clinical trials has prompted the FDA to grant them clearance to expand their current Phase 1/2a trial from 13 to up to 35 patients.

Asterias can now enroll patients with both AIS A (complete injury) and AIS B injuries and has expanded the age range of trial participants to 18-69 years. Dr. Wirth added that the goal of this trial is to rescue some of the motor function in cervical SCI patients so that they can go from needing full time care to being able to carry out some functions on their own. He also indicated that these patients will be monitored for 15 years to evaluate the safety and success of their treatment.

We at CIRM are encouraged by these early positive results and hopeful that this clinical trial will result in a stem cell treatment that will improve the lives of SCI patients.


Related Links:

New Video: Spinal Cord Injury and a CIRM-Funded Stem Cell-Based Trial

Just 31 years old, Richard Lajara thought he was going to die.

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Richard Lajara, the 4th participant in Geron’s stem cell-based clinical trial for spinal cord injury.

On September 9, 2011 he slipped on some rocks at a popular swimming hole and was swept down a waterfall headfirst into a shallow, rocky pool of water. Though he survived, the fall left him paralyzed from the waist down due to a severed spinal cord.

Patient Number Four
At that same time period, Geron Inc. had launched a clinical trial CIRM helped fund testing the safety of a stem cell-based therapy for spinal cord injury (SCI). It was the world’s first trial using cells derived from human embryonic stem cells and Lajara was an eligible candidate. Speaking to CIRM’s governing Board this past summer for a Spotlight on Disease seminar, he recalled his decision to participate:

“When I participated with the Geron study, I was honored to be a part of it. It was groundbreaking and the decision was pretty easy. I understood that it was very early on and I wasn’t looking for any improvement but laying the foundation [for future trials].”

A few months after his treatment, Geron discontinued the trial for business reasons. Lajara was devastated and felt let down. But this year the therapy got back on track with the announcement in June by Asterias Biotherapeutics that they had treated their first spinal cord injury patient after having purchased the stem cell assets of Geron.

Getting Hope Back on Track
Dr. Jane Lebkowski, Asterias’ President of R&D and Chief Scientific Officer, also spoke at the Spotlight on Disease seminar to provide an overview and update on the company’s clinical trial. A video recording of Lebkowski’s and Lajara’s presentations is now available on our web site and posted here:

As Dr. Lebkowski explains in the video, Asterias didn’t have to start from scratch. The Geron study data showed the therapy was well tolerated and didn’t cause any severe safety issues. In that trial, five people (including Richard Lajara) with injuries in their back received an injection of two million stem cell-derived oligodendrocyte progenitor cells into the site of spinal cord damage. The two million-cell dose was not expected to show any effect but was focused on ensuring the therapy was safe.

Oligodendrocyte Precursors: Spinal Cord Healers
As the former Chief Scientific Officer at Geron, Lebkowski spoke first hand about why the oligodendrocyte precursor was the cell of choice for the clinical trial. Previous animal studies showed that oligodendrocyte progenitors, a cell type normally found in the spinal cord, have several properties that make them ideal cells for treating SCI: first, they help stimulate the growth of damaged neurons, the cell type responsible for transmitting electrical signals from the brain to the limbs.

Second, the oligodendrocytes produce myelin, a protein that acts as an insulator of neurons, very much like the plastic covering on a wire. In many spinal cord injuries, the nerves are still intact but lose their myelin insulation and their ability to send signals. Third, the oligodendrocytes release other proteins that help reduce the size of cysts that often form at the injury site and damage neurons. In preclinical experiments, these properties of oligodendrocyte progenitors improved limb movement in spinal cord-severed rodents.

Together, the preclinical animal studies and the safety data from the Geron clinical trial helped Asterias win approval from the Food and Drug Administration (FDA) to start their current trial, also funded by CIRM, this time treating patients with neck injuries instead of back injuries.

The Asterias trial is a dose escalation study with the first group of three patients again receiving two million cells. The trial was designed such that if this dose shows a good safety profile in the neck, as it did in the Geron trial in the back, then the next cohort of five patients will receive 10 million cells. In fact, Asterias reported in August that the lower dose was not only safe but also showed some encouraging results in one of the patients. And just two days ago Asterias announced their data monitoring committee recommended to begin enrolling patients for the 10 million cell dose.  If all continues to go well with safety, the dose will be escalated to 20 million cells in the third cohort of five patients. While two million cells was a very low safety dose, Asterias anticipates seeing some benefit from the 10 and 20 million cell doses.

Changing Lives by Increasing Independence
Does Lebkowski’s team expect the patients to stand up out of their wheelchairs post-treatment? No, but they do hope to see a level of improvement that could dramatically increase quality of life and decrease the level of care needed. Specifically, they are looking to see a so-called “two motor level improvement.” In her talk Lebkowski explained this quantitative measure with the chart below:

“If a patient is a C4 [meaning their abilities are consistent with someone with a spinal cord injury at the fourth cervical, or neck, bone] they will need anywhere from 18 to 24 hours of attendant care for daily living. If we could improve their motor activity such that they become a C6, that is just two motor levels, what you can see is independence tremendously increases and we go from 18 to 24 hour attendant care to having attendant care for about four hours of housework.”

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Small improvements in movement abilities can be life changing for people with spinal cord injuries.

It’s so exciting the field is at a point in time that scientists like Dr. Lebkowski are discussing real stem cell-based clinical trials that are underway in real patients who could achieve real improvements in their lives that otherwise would not be possible.

And we have people like Richard Lajara to thank. I think Dr. Oswald Stewart, the Board’s spinal cord injury patient advocate, summed it up well when speaking to Lajara at the meeting:

“Science and discovery and translation [into therapies] doesn’t happen without people like you who are willing to put yourselves on the line to move things forward. Thank you for being in that first round of people testing this new therapy.”