Good stem cell news on trials, FDA, cool new papers & more


Guimarães-Camboa, et al, Cell Stem Cell figure

In the whirlwind that is the stem cell and regenerative medicine world, there are many concerning things that need attention, but also good stuff happens too and this post focuses on the positive.

The Asterias spinal cord injury clinical trial, a phase 1/2a trial called SCiStar, continues to make encouraging news with a clean safety profile and additional hints at possible positive indicators of efficacy. With the usual, important caveats such as that this is early and it is not an RCT, the SCiStar momentum is positive. I’m excited to see what the future holds for this one including from an RCT. You can read my interview from last month with Asterias leadership here.

I remain very enthusiastic about ViaCyte’s trial as well using a stem cell capsule product for treatment of Diabetes. Their joining forces with BetaLogics a year ago just made their position even stronger.

I’m going to do a post soon on an analysis on the total number of stem cell and regenerative medicine trials compared to historical data I collected. Stay tuned on that. I’m guessing it’ll be good news.

Recently, we also saw evidence of fast action from FDA in response to the 21st Century Cures Act in terms of providing a clear document on Regenerative Advanced Therapy designations and applications. It’s still unclear how the Cures stem cell provisions will play out, but I consider quick, clear action from the FDA to be a positive. I wish they were this fast on other stuff like dealing with stem cell clinics marketing unapproved drug products.

There have been a number of cool papers recently that I recommend reading:

Top 20 Stem Cell Predictions for 2017

stem cell crystal ball

Stem cell crystal ball

Each year I make a list of predictions for the stem cell and regenerative medicine field for the coming new year. Later in this post I list my top 20 stem cell predictions for 2017. In looking at my past predictions I realized this will now be my 7th year doing stem cell/regenerative medicine yearly predictions.

You can see below links to these predictions for past years, which sometimes seems rather far removed from today and in other cases strike me as strangely apropos of our times.

What will 2017 bring? Below are my top 20 predictions in no particular order except starting with a few hopeful visions for the coming year.

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Asterias interview: stem cell spinal cord injury trials advance

Recently I had the opportunity to talk with the leadership of Asterias, a California biotech doing exciting clinical research using stem cells as the basis for treatment of spinal cord injury. The interview covers the past (Geron patients), present, and future. I spoke with Asterias President and CEO Stephen Cartt and CMO Edward Wirth.

How are the Geron patients doing?

Asterias: They are doing well. We have to remember that they got the low dose (2 million OPC1 cells) and we estimated that an efficacy dose was more like 10-20 million cells. The good news is that the safety profile is very strong. The trial has 15 years follow up including 5 years of MRIs and then phone follow up. There is so far sustained evidence of prevention of cavity formation in 4 out of 5 patients, which suggests durable engraftment. Out to 1 year no evidence of an antibody or T cell response to OPC1 cells. We will look at that out to 5 years. No masses or tumors or health issues attributable to cells. We are very excited by those safety data, which were also submitted to the FDA.


Dr. Richard G. Fessler, professor of neurological surgery at Rush University Medical Center in Chicago, is shown here making final preparations to inject 10 million AST-OPC1 cells into a spinal cord injury patient in August 2016. Dr. Fessler is the lead investigator of the SciSTAR study looking into AST-OPC1 as a treatment for spinal cord injury.

Are AST-OPC1 heterogeneous?

Asterias: The overwhelming percentage of cells are OPCs. In the spirit of full disclosure there are some other characterized cell types in the mix too. We are working to more fully characterize those cells. In the old days a lot of characterization was done by immunostaining. Now we are doing RNA-Seq and other more up to date studies. An interesting question is: do any of the other minor players (cell types) contribute?

What happens with the AST-OPC1 prior to Day 0? Is it a thaw-and-go kind of situation or do the cells get cultured for a while?

Asterias: The cells are thawed and washed (to remove cryopreservative) on the day of surgery. This takes 2-3 hours and is typically done in the morning. STAT gram stain is also done and once they pass, they are then released to the OR for injection. Another sample is sent for 14-day sterility test. So there is no expansion of the cells prior to injection, just washing and resuspension into the injection medium. We find there’s about 80% viability.


Can you update us on the spinal cord injury trial? How do we tell the difference between a therapeutic effect and spontaneous recovery?

Asterias: So this is something that has been investigated in detail by the SCOPE (spinal cord outcomes partnership endeavor) group with Dr. John Steeves Professor at UBC and Andy Blight, the Acorda therapeutics CSO. There have been some papers published. What is the SCI rate of recovery with standard of care? The majority of patients with an American Spinal Injury Associate (ASIA) Impairment Scale Grade A injury (known as an AIS A injury) will recover 1 motor level on one side of the body. Very few of these patients spontaneously recovery 2 motor levels, even over the longer term. With OPC1, our goal is 40-50% of patients having >= 2 motor levels on one side of body, which is well beyond typical spontaneous recovery, and so far by day 90 some of our patients in the 10 million cell cohort had already recovered 2 motor levels (that was our 6 month target). We haven’t tested the 20 million dose yet, but believe there’s potential for further improvements with this higher dose. The dose response related to motor score is encouraging so far with respect to the 2 million and 10 million cell doses.

Can you tell me more about the complete thoracic versus subacute cervical trials? What are the differences in the patients for instance?

Both studies tested patients with severe impairment. The thoracic study and the first three cohorts of the cervical study were in patients with AIS A injuries, which is complete loss of motor and sensory function below the site of injury. We also recently got permission to expand the study to two additional cohorts of patients with AIS B injuries. These patients have complete loss of all motor function but some preserved sensory function below the level of their injury.

Both studies are similar.

One difference between the original thoracic and the current cervical study is timing of delivery of OPC1. In the original study in thoracic injuries, Geron injected OPC1 within 7-14 days of injury; in the ongoing Asterias cervical study, there is a 14-30 days post-injury window. 14 days is extremely tight, while 14-30 is more feasible. Most of the patients got it close to the 30-day cutoff. The reason scientifically we are focusing on the subacute window is that there is a sense we will obtain better engraftment in that period. We want to avoid the early inflammation and the scar tissue formation period (begins ~3 months). We could push the window out a few more weeks. The rationale for also going into cervical is that if you can mediate anatomical repair, via OPC stimulating endogenous repair, collectively over several segments, if that can mediate functional repair, it can have a huge impact on a person’s quality of life.

Any hope for lower extremity function restoration?

Asterias: It’s a tall order for the severe injury cases such as patients with AIS A injuries. In these patients we believe improvements in upper extremity function are far more feasible. In less severe, AIS C injuries (in which some level of both sensory and motor function are preserved below the level of the injury), there may be a good chance for some leg motor function recovery.

Any side effects including of immunosuppression?

Asterias: There have been no clear negative effects of immunosuppression. Going into the study the primary concern regarding immunosuppression was could infections be more frequent or worse? We tried to limit the immunosuppression to low dose and short term in order to minimize this risk. So far in the study we haven’t seen any evidence of increased infections, which is encouraging.

What about company policy regarding trial participants and the media? We’ve seen at least one patient talking to the media.

Asterias: Several of our patients have chosen to make public statements regarding their participation in our study. This is their choice to make. So much has been taken away from their lives. They’ve seen benefit so understandably they like the idea of expressing what they’ve experienced and they want to educate other patients. Their doctors communicated to us that the patient is interested in talking. There are HIPPAA considerations.

What are your future plans and do they include RCTs?

Asterias: The logical next phase is a randomized controlled trial. We’re currently enrolling in our single arm, open label trial for the AIS A 20 million cell dose cohort and the AIS B 10 million cell cohort (and later 20 million). That is expected to wrap up Q3-4 next year. As the data come in, we can make plans.

The next big readout is January of 2017 when we should have cumulative 6-month data for the AIS A patients at 10 million cells. 5 patients.
As this and other data from the subsequent cohorts become available, we’ll examine data, talk with investigators, the FDA, etc. to determine our plans for subsequent trials.

Do you have any non-SCI-related work in the pipeline?

Asterias: OPC1 could be helpful for other indications. We have done some preclinical work related to MS and certain kinds of stroke, which have been encouraging. Some pediatric conditions. Overall, we want to get that first clinical win before we pursue other areas.

Disclosure: I have no financial ties to Asterias.

Top 10 Google Stem Cell News Stories: Perspectives

What does Google think (if Google does indeed think) are top 10 stem cell news stories right now?

I took a screen shot below.

Here are some thoughts on those stories.


First, lung organoids are neat, but they have been grown before by several groups. Why is that the top story? I’d have to ask Google. Better PR? Still looks interesting and could have real impact for lung disease in the future.

The second story is on the transplantation of allogeneic IPS cells into monkeys without immunosuppression.This is an important finding with clinical impact from Dr. Takahashi’s group.

That third story seems odd to me. Seems like an over the top claim.

The fourth one with its “for the first time” I’m not so sure about and number five seems to be on the same story. I have doubts about that trial given the lack of detail and the potential for harm to patients. It sounds premature.

Then we have cancer stem cell stories at number six and another at number eight.

Number seven and ten both refer to the experience of one patient in the Asterias stem cells for spinal cord injury trial. Number ten’s headline is dubious from a scientific perspective with its “as a result” claiming the stem cells made the man better for sure. I really hope that’s true, but we don’t know yet although more recent data on more patients is encouraging. Controls are needed in the long run to iron things out.

Number nine is about stem cell clinics. It seems to be the only one mentioning the historic FDA stem cell meeting this week.

Early, but encouraging data from Asterias on stem cells for spinal cord injury

asteriasAs I posted recently, Asterias Biotherapeutics has had good early safety results so far in its historic stem cell trial for spinal cord injury and now the company presented some early, encouraging hints at efficacy.  However, a caveat here is that this is not an RCT (randomized controlled trial).

Ed Wirth, CMO of Asterias, presented the early data at the 55th Annual Scientific Meeting of the International Spinal Cord Society. You can take a look at the very interesting talk slides here. Asterias is a subsidiary of BioTime.

According to the press release (PR) from the company, while only 4 of 5 patients are 90 days or more after treatment, all patients have shown some improvement in motor function and a subset have a substantial improvement, meeting the target at this point. This trial is funded in part by CIRM so kudos to our state’s stem cell agency on this.

MIT Tech Review is on the story to for more background. I’ve also posted from Dr. Wirth’s PowerPoint the study design image below.asterias-sci-stem-cell-study-design

Bottom line. Overall, I think this development is encouraging. While still early in the clinical trial and drug testing process, the fact that there is a good safety profile and early indications of possible efficacy yield real hope. Still, it is important to be cautious in interpreting early data. We’ll all need to follow this trial and then look for future RCT results to clarify how promising this drug is overall in the long haul.

I’ve posted the key bullet points from the Asterias PR below the fold.

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