Upbeat Update from Duke on Stem Cell Autism Trial, but Questions Remain

Dr. Joanne KurtzbergIn 2014, I reported on a groundbreaking, but debated Duke stem cell-based clinical trial being launched for autism.

Where does that trial stand today?

The cord blood trial has continued. It is led by Dr. Joanne Kurtzberg, whom I interviewed about cord blood stem cells back in 2013 (see part 1 and part 2), where she provided some fascinating background. It is also notable that on the stem cell autism trial front, other efforts are underway as well.

This week at the World Stem Cell Summit, Dr. Kurtzberg gave us an update on the cord blood stem cell trial for autism. You can see the trial listing for details here. The Marcus Foundation and PerkinElmer, Inc. are collaborators.

The data presented seem very encouraging. In addition to evidence of efficacy, the cord blood transplants were reported to be safe so that’s encouraging as well.. She reported improvements with cord blood treatment of autistic patients across a number of readout assays (p values in parentheses): decreased sensory sensitivity (0.03), increased social communication (0.007), decreased repetitive behavior (0.01) and a decrease in social withdrawal although not significant (0.09).

These results sound exciting. However, as a biomedical scientist I’m still grappling with how an IV infusion of stem cells could help autism.

What could be the mechanism?

Since we do not know the causes of autism spectrum disorder and there are likely to be numerous causal factors of both genetic and non-genetic natures, it is difficult to define how a systemic cellular treatment could meaningfully benefit autistic children. One notion is that a subset of the cord blood cells cross the blood brain barrier, enter the brain, and somehow do something positive for autism there.

While I’m not clear on what that positive thing might be that is specific to autism, Dr. Kurtzberg showed a FISH staining image where at least some IV administered cord blood cells appeared to have entered the brain. This suggests that the Duke team is thinking at least in part of a direct mechanism.

I believe this particular example was in an allogeneic setting with male cells given to a female patient and the male cells were detected by DNA FISH. There has been much skepticism over the years on whether IV administered stem cells of any kind cross the blood brain barrier (BBB) and how they might do so. In some pathological states it has been shown that the BBB is compromised allowing for stem cells to enter the brain from the vasculature, but I’m not aware of the BBB being compromised in autism. Since there is no apparent inflammation in autism it also remains unlikely that the cord blood stem cells would home in on the brain.

Many open questions remain such as those mentioned above. Also I would like to learn more about the specific numbers of cord blood cells that entered the brain including info such as engraftment rate, timeline, etc. This may have been presented and I just missed it as I was multitasking up a storm at the meeting.

The bottom line for me is that I’m glad to see encouraging results on the autism front, but I still have some skepticism because I do not see a convincing mechanism. Hopefully things will continue on a positive trend and provide more clarity.

60 thoughts on “Upbeat Update from Duke on Stem Cell Autism Trial, but Questions Remain

  1. Knoepflerr, you know this is outright quackery. Why dont you say that in this case? Just because a reputed university in involved and a the research involves academic scientists and clinicians does not diminish the mindless human experimentation that is not based on sound science, rigorous preliminary evidence or even a decent theoretical basis. This is exactly the same kind of shot in the dark and hand waving that you accuse private stem cell clinics of engaging in and call it quackery, dangerous and putting lives in danger. What if the cord blood stem cells enter brain and by some later trigger cause inflammation?? Why is not 60 Minutes jumping on this story as quackery?? This is the double standard that we patients are so used to these days from academic research scientists and people like you and we find this disgusting.

    • @ALSadvocate,
      I don’t think you speak for all patients and your views are rather extreme. The Duke study is not like predatory stem cell clinic quackery at all.

  2. Professor Knoepfler,

    Is there a chance that the anti-inflammatory factors released by the stem cells gives targeted relief to the area of the brain affected and gives the system some room to recover the energy used in the coping systems? How long are the results lasting and what is the follow up? How are the cells administered? Are there any cell changes that remain after 3 months and do these contribute to efficacy. Also is there anything in the prep work of the patient that could contribute to overall efficacy?

    • @Amy,
      I guess that is formally possible, but to my knowledge there is no convincing evidence of a consistent role for inflammation in the brain in autism spectrum disorders. I believe the cells in this case are infused systemically. The results so far are only over a period of months up to one year I believe so still preliminary. Dr. Kurtzberg indicated as much in her talk. I’m not sure about answers to the other questions yet.

  3. Paul, In our testing of ASD Children in Eastern Europe, we find mots have high heavy metals (especially Al and CU) and pathogen loads. We also show low levels of growth factors like BDNF and GM-CSF. This is coupled with high levels of Gap Adhesion Proteins. Perhaps a root factor of ASD is “leaky BBB” and ASD Children are undergoing low level neuro-immune/inflammatory response assault? At any rate, maybe this therapy is working, in part, to moderate tghis response.

  4. @ Pete Shuster. Maybe you deserve a Nobel Prize for your work when completed and reproduced, Mr.Shuster. But my point is why was the trial allowed to proceed with humans without prior testing of any of such possibilities, like rigorous science would call for, especially when Ms.Kurtzberg herself expressed grave concerns for therapies targeting brain.

  5. @ Paul. Given that you were not able to observe Dr. Kurtzberg’s entire presentation, it would be great if you could reach out to her once again for a Q&A on this particular study, to seek more information and clarity and share with your readership. I was comfortable with what I observed in the complete presentation and Dr. Kurtzberg did address these questions with honest answers.

  6. Knoepflerrr, I speak for the patients that I know and by common sense it is impossible for me or anyone to speak for ALL patients, given such diversity of diseases, or even for the ALS community, where patients are free to entertain diverse view points, unlike the regimented views of folks like you in the academia. But you claim to speak for the scientific community as an ‘insider’.
    I think your views are even more extreme than mine, despite the outcomes that patients have been experiencing or many years. I frankly could care less for your opinion on my views. What I care about is how people like you erect enormous barriers for patients, on top of the tough situation they are already in, for largely self-serving purposes. Despite me repeatedly pointing out this patient perspective to you and others, you guys just dont seem to get it.

  7. Knoepflerr, as to your comment…you mischaracterize my comments as talking about “predatory stem cell clinic quackery”. Tell me something..aside from the fact that patients are not paying for the trial (but tax payers are), how is Duke trial conceptually or scientifically not a quackery. You do understand that there are several “unlicensed clinics” across the world that offer cord blood stem cells for Autism. If treatment of Autism with cord blood stem cells is quackery (as you have posted in past years) which has no scientific basis, is it not quackery even if Duke does it?. What new information do we have to justify such a human trial, I would love to know. If it is not quackery, are you saying that what the “unlicensed clinics” are doing actually has a chance to benefit patients?? I have no idea what you are saying at this point.

    • The study itself says on the rationale that it is focused on inflammation in the brain itself so would seem to rely on (1) autism being substantially due to brain inflammation, and (B) cells getting into the brain in large numbers that can fight inflammation. Here’s what they wrote:
      “In this study, the investigators hypothesize that infusion of a patient’s own umbilical cord blood cells (UCB) can offer neural protection/repair in the brain and reduction of inflammation associated with this disorder.”

  8. Dear Paul, I do not understand this part: “I believe this particular example was in an allogeneic setting with male cells given to a female patient and the male cells were detected by DNA FISH. ”

    Do the researchers took a biopsy of the brain and do FISH on the specimen? So they could conclude that the given UCB cells homed to the brain?? In my opinion, it is pretty weird.

  9. Knoepflerr, here is a news release from Duke about the autism study at http://psychiatry.duke.edu/news/news-archive/marcus-foundation-grant: “The project will consist of a series of clinical trials using umbilical cord blood cells to treat a total of 390 children and adults with autism, 100 children with cerebral palsy and 90 adults with stroke. Based on previous research, Kurtzberg and Dawson hypothesize that cord blood may promote repair of dysfunctional or damaged areas of the brain.” (the specifics of previous research is not listed)

    The total money involved for Duke in this is $41 million over 5 years and patients with ALL THREE three conditions will be treated ALL with the umbilical cord blood stem cells….Now where else have we heard of such quackery before….that the same cells can do anything and everything and somehow “know” what to do and “know” where to go to repair…..thats right…the ones you call “predatory stem cell clinics”. They charge $20,000. In this Duke news release, the money involved per patient is over $70,000 and each patient is getting a single dose of umbilical cord blood stem cells. Now, without rushing to mindless defense of your colleagues by default, can you Knoepflerr, tell us how you think that the same cells can treat all these conditions….theoretically and if there is the data backing that up, since you are so vocal about these issues and patient’s safety and human rights.

  10. @ALSadvocate,
    I’m not a fan of the idea of any one particular type of stem cell as a kind of semi-universal treatment for many diverse conditions. It is hypothetically possible that one kind of stem cell could work for more than one condition, but the odds get longer as one proposes more and more conditions. The bottom line is to prove one way or another. Does it work for this? Is it safe? If one is going to do this kind of clinical trial in humans, then that team should have strong data from animals. I need to do more reading on the published animal studies in this area. To call something “quackery”, given the intense nature of that word, I believe you need concrete evidence rather than just accusations.

    As to the financial side of this, the money at Duke is to run the trial, do the studies, etc. The money at clinics is a wholly different matter as it is all about profit. Also as I think you yourself pointed out, patients in the studies at Duke don’t pay so the source of the money is completely different.

  11. @ Jeanne. The FISH was not done as a biopsy. It was done during an autopsy over a decade ago on a patient who had received an opposite sex cord blood unit. The patient was ablated, but ultimately succumbed to GVHD.

    • @Super,
      Do you know if this FISH data on cord blood cells getting in the brain was published? If so, can you provide a link? If not, have you heard about the extent (e.g. was the engraftment quantified?) of cord blood cells that were observed in the brain?

  12. Interesting to see another registered clinical trial trying to establish the value of stem cells in diseases. In another framework this has been described as unregulated, risky and taking advantage of desperate patients and families. But ALSadvocate, despite an unnecessary keyboard-warrier style, raises a point.

    Is the Duke study based on a better insight than the unregulated for-profit stem cell clinics? I suspect not because both can cite Dr. Kurtzberg’s work as a rationale – so what’s the difference?

    The difference, as often discussed on this blog, is that clinical trials attempt to answer questions of efficacy and mechanism with multiple independent endpoints and cohorts of patients. Compare this to for-profit unregulated clinics who will not publish anything scientifically valid as they only report selected cases, if at all. This is called marketing and is perfectly legal.

    Now ALSadvocate is itching to say that this trial will also not give us those answers – and would be right as this is only a safety study. Paul writes, “In addition to evidence of efficacy..” but this study will not produce data on efficacy that can be definitively attributed to the therapy as there is no control cohort.

    Dr. Kurtzberg herself said, “To really sort out if stem cells can treat these children, we need to do randomized, controlled trials that are well designed and well controlled.” So in summary, it is way too early to even speak about efficacy and a phase II study will give us more insight.

    Does this mean the trial is “quackery” – no, of course not. It is what we all want to see for new stem cell therapies. Does it mean unregulated stem cell clinics advertising cures for autism are peddling “quackery”? Potentially not, but they cannot provide evidence for their claims either and they’re also not contributing to the solution – they are simply out to make money and that’s also not illegal.

    Duke is not making money out of the trial and is contributing to understanding. Based on the same starting position, unregulated clinics are making money out of patients by telling them something that is not yet proven. That’s not quackery.

    Frankly, I do not believe that Kurtzberg will find a generally efficacious treatment – but if her phase II cohorts are carefully chosen, there may be a subpopulation of responders, such as those for which chronic inflammation is key.

  13. Knoepfkler, on your “concrete evidence” comment…are you providing such evidence when you talk about private clinics…have you provided concrete evidence in the past for all your even more expansive accusations of all the clinics under the sun that you label as non-compliant. Surely not. Look…I am not here to go back and forth with you on hollow arguments. Please stick to the substance of the discussion.

    In the Duke study case, its not only me but several academic scientists and clinicians also dismiss the study as premature and not supported by scientific evidence. In exactly the same context, you and a multitude of academic scientists and science commentators are calling treatments offered by private clinics as quackery, and that now extends to the Duke study as well.

    Now, the money issue…its best if there is a public disclosure of how the money is being spent so everyone can judge for themselves, if the argument on your side is that all the money is to “do the study” and “run the trial”. Exactly where the money is spent on doing the study and running the trial should be open to public for such a controversial study criticized by many. At this point you are totally speculating about the use of funds.

    The fact is that such treatments have been available from private clinics for a LONG time now and Ms.Kurtzberg study has actually given a big boost to the private clinic claims over the years, without any new or ground breaking data available to justify such experimentation, especially when Ms.Kurtzberg goes on 60 minutes and talks about the dangers involved. How has she ensured that the dangers have been mitigated, by her own assessment of the issue?

  14. @ALSadvocate – you ask how has she ensured that the dangers have been mitigated. Maybe you’re not familiar with clinical trials but a phase I clinical trial is done to show that the procedure is safe, And that’s what they are doing in this study. As far as I know nobody else has done this for autism although some clinics are offering treatment for autism with stem cells.

  15. To add a response to ASLadvocate, I think a main difference between the Duke clinical trial and the for profit clinic approach is that the patients in the duke trial are likely getting something like a common product: presumably collected, stored, analyzed and administered under a specific set of conditions. At least the comparison will be apples to apples among patients. In the for profit model, each company makes, analyzes and infuses according to its own (likely very opaque) protocols.

    What is infused really matters, and the for profit model isn’t amenable to knowing what is in the infusion bag.

  16. All private clinics should be obliged by law to publish their data. This would lead to more transparency for patients and will help science to move forward. So a win – win – situation.

  17. “The project will consist of a series of clinical trials using umbilical cord blood cells to treat a total of 390 children and adults with autism, 100 children with cerebral palsy and 90 adults with stroke.”
    They try to treat stroke patients, too. So I would like to know, what is the big difference to the therapy Gordie How and Bart Starr received? Yes, I know, we discussed this so much, and I know, that it is not likely, that Gordie had a benefit of the treatment as I learned here. But where is the big difference. Gordie received othere cells (MSC). But if they are so sure that a stem cell therapy can not help stroke patients, why do they do this trial???

    I agree it should make no difference, if a so called “predatory” stem cell clinic is doing a trial or another one.

  18. Thanks, I think autism being substantially due to brain inflammation might be better stated as “brain inflammation is a symptom that is excaberated in autism”.

    In this case the study is worth doing as each inflammatory cascade can rob an autistic person of functional capacity and increase hyper sensory reactions which decrease socialization and quality of life.

    If there is a tipping point where the system can recover and operate within normal limits with properties released from the stem cells it makes sense to explore this. Accepting all ages/ severity etc can help to rule in/rule out conditions where this would be of benefit.

    Was there not some success with cerebral palsy in some children? If yes, then working with autistic children to see if a similar mechanism is at work is logical.

    As to all the clinic V academic byplay. Same standards for all. There are safety and clinical practice guidelines to meet and approvals to show that there is compliance. Anyone that chooses to do the research needs to show they meet the standards. We have permits and codes to make even our buildings, bridges, electronics, etc safe and is not a human body of greater importance than these?

    I agree transparency and disclosure for all expenditures of public monies is imperative and that all trials need to be registered with all results reported and made public.

  19. @Mahindra
    Tell me how is safety assessed in this study exactly?? You seem to understand it better than me.

    Is it that the patients did not die from the treatment?? Did they actually think that patients own stored cord blood stem cells would harm the patients when given back to them. What risks are they measuring in the first place?

  20. @ALSadvocate
    The aim of a phase I clinical trial is to test a new drug in a small group to evaluate safety, identify side-effects and to determine a safe dose regimen. As many studies using autologous umbilical cord blood have already been done in different patients, the likelihood of serious adverse effects (SAE) is reduced, but not eliminated as it hasn’t been done in this particular patient group with so many cells (up to 50 million cells / Kg body weight). Hence, safety and tolerability must still be shown.

    You asked if patients own stored cord blood cells would harm patients when given back to them. It’s quite possible that this could be harmful under certain conditions. The wrong assumption that some people make is that because the cells are your own, they will be safe. Stem cells can differentiate into unwanted (ectopic) tissue types or form tumors and there are reports of such events. So it is still essential to perform safety studies. Maybe this also answers your question about the difference between the Duke study and unregulated clinics, which don’t do safety studies before treating patients.

  21. @Mahindra
    You didnt answer my questions. How are the side-effects specifically estimated in this study? What are the parameters tested?
    I would rather you spend some decent time looking at the study, understanding it for your own benefit and perhaps educate us about this particular study, and not talk in generalities. If, as you say, there is many known dangers in infusing so many millions of stem cells, how was safety monitored with reference to all these known dangers??
    If there was no SAE, you seem to be convinced there are no safety concerns at all??

    Apart from the safety issue, the main question that I and several scientist are asking is more to do with the lack of scientific evidence to support such an approach by intravenous infusion. Consequently, it IS quackery and a troubling trend of human experimentation without solid supporting studies. You people call this as putting lives in danger when private clinics do it and that characterization must also extend to this study. Got it?
    For example, if the study shows no phase I safety issues, do you think the study should proceed to full-scale clinical trials that involves huge sums of money, based on just clearing safety hurdle, without any solid scientific data? Is this how you do your science?

  22. @Mahindra
    A study with phase 1 only makes sense, when you are planning phase 2 and phase 3. Why is your safety study safer than a study by another clinic?
    You treat humans, they treat humans …? I don´t understand your argument.

    The stem cells might have entered the brain. Does this fact maybe change your opinion about the treatment of Gordie Howe? If the cells could enter the brain and show positive effects, why maybe not for Gordie Howe?

  23. @ALSadvocate
    Thank you for your concern about my understanding of the trial, but I believe I am cognisant of the key features I need to make a conclusion and have some experience in clinical trial management to fall back on.

    I have no insight into the specifics of the AE/SAE assessments used in this trial, but for any phase I there will be a battery of cardiovascular, metabolic, neurobehavioural, immunological and hematology tests that reveal ontological perturbations. In addition the study contains a range of potential therapeutic readouts, which while not specifically designated as safety endpoints, will serve to assess whether disease in this patient group is progressing or stabilizing. You can find a list of these on the clinicaltrials site under “Current Other Outcome Measures”

    “If there was no SAE, you seem to be convinced there are no safety concerns at all?”
    Absolutely not – safety in phase I is only valid for the drug regimen tested in phase I. Likewise in phase II and III it is broadened and eventually safety is aligned with the target patient population and the therapy. But even here there is no guarantee of long-term safety and hence, years of follow-up is necessary.

    “the question that I and several scientist are asking is more to do with the lack of scientific evidence to support such an approach by intravenous infusion.”
    There is a lot of data that cord blood cells are immunosuppressive and support regeneration. If this is sufficient to prevent inflammatory aspects of autism disorders, some patients may benefit.

  24. “There is a lot of data that cord blood cells are immunosuppressive and support regeneration. If this is sufficient to prevent inflammatory aspects of autism disorders, some patients may benefit.”

    I just asked, why do you use cord blood and not MSCs like other clinics do?

    And could you please let us know, where to find the data?, you mentioned above

    Please let us know.

  25. @MT
    “You treat humans, they treat humans …? I don´t understand your argument.”
    I said a phase I study by Duke is better than no study at all by an unregulated stem cell clinic. Humans are not all the same and there can be huge differences in drug safety between children compared to adults, women compared to men, Asians compared to Europeans, and so on.

  26. @Mahindra
    Well…I looked at the primary, secondary and other outcomes before I commented…unlike you who even now in response to my comments did not take the time to look first before responding to my comment…and spit out some more irrelevant generalities. So, for your edification..in this study the primary outcome is Non-serious/Serious Adverse events and after that secondary and other outcome measures are all behavioral outcomes related to the disease spectrum. Even I, from the business world, can understand that this is not designed to measure the very same dangers that Ms.Kurtzberg herself expressed concerns about nor does it even touch the surface of the host of problems you mentioned above in your previous comment. So based on utterly inadequate measure of outcomes, which does not assess the dangers you mention, you propose to go to the next level of phase II, phase III, to experiment on larger groups of patients??

    Your reason why patients could benefit from this is speculative at best and tax payers are paying for scientific research to be conducted responsibly and at the highest levels and not by following untested speculation about how this “may” benefit. It may be fun for you to test it, but we as tax payers and patient advocates take an exception to mindless human experimentation, without the fundamental understanding of the disease process and why such an approach is the best.

    Even an fool can see that the same cells cannot possibly be used for treating Autism, cerebral palsy and Stroke, which you guys have said so many times in relation to advertisements by private clinics…..but now you are trying your best to convince us that when YOU GUYS do this, it is somehow to be considered as a great discovery path that you guys are on. I sure hope you dont take us as fools, Mr.Mahendra, never mind your experience in clinical trial management.

    • @ALSadvocate,
      I appreciate how you’ve added to this discussion, but your angry, insulting tone to those of us having this dialogue is not helpful to put it mildly. Your undermining your own arguments and points by your way of communicating. Also, I allow anonymous comments on this blog, but I would– would you be so willing to take the low road if you weren’t anonymous?

  27. @Mahindra,
    thank you for so many answers, but do you have an answer to my question, too. Several experts say MSCs would be a better choice, why do you take cord blood? I would like to understand.

  28. @Mahindra
    Al Sadvocate wrote: “Even an fool can see that the same cells cannot possibly be used for treating Autism, cerebral palsy and Stroke …”
    This was my question above, too (you never answered). You treat stroke or try to treat stroke with stem cells. How should this work? I learned from some experts here, that the therapy Gordie Howe received seems to be unserious. But what is the difference to your therapy? I am no expert, but sorry, I don´t understand the difference? Could you please explain this to us?

    you wrote so much about the therapy Gordie Howe received, but where is the big difference to this therapy ?

    I don´t see a difference but one clinic used MSCs and the other cord blood.

    Please let us know.

    • @Richie,
      Gordie Howe received two kinds of stem cells: fetal neural stem cells and MSCs. I believe the former were infused systemically and the latter directly into the CNS, but I’ll have to double check that. So no cord blood. Also in stroke the BBB is compromised so that is a big difference and there is defined, serious brain injury in patients like Howe who had multiple strokes it was reported. In children with autism by contrast their brains are largely normal and to my knowledge no one knows the pathophysiology of autism spectrum disorders, making it harder to treat and to understand how something could potentially make it better. if you don’t know what’s wrong at the molecular and cellular levels it’s difficult to make a convincing argument for how to fix it and how you would even know it is fixed other than cognitive/behavioral changes. Paul

  29. @ALSadvocate
    I don’t think you understood what I wrote as you’ve just repeated it.

    “primary outcome is Non-serious/Serious Adverse events” – yes, and I listed for you what these outcomes could entail for standard safety analyses.

    “secondary and other outcome measures are all behavioral outcomes related to the disease spectrum” – and I described these as patient specific potential therapeutic readouts, which may also provide safety insights

    Good that we agree on the study structure and I’m sorry if my descriptions don’t fit exactly what you want to hear, but I wrote so that others could understand it too. You should try to be a little more open in a discussion and maybe you can also glean some more understanding.

    FYI I have coordinated around 30 clinical trials in several countries and have a good understanding of clinical trial descriptions. Nevertheless, appreciate your edifying instruction 😉

    Sorry I can’t offer you solace for the rest of your post but I wish you well and hope you can find some comfort in your quest.

    @Richie – a good question and there are purported benefits to both MSC and cord-blood (and others). I’m not an advocate of any particular type and we have only used stem cells for research purposes in work to develop liver cells for toxicology. We used cord-blood because the cells are not burdened by a lifetime of exposure to environmental toxins, drugs, or the usual stresses of life in general. Each type may also be more or less immunosuppressive or secrete specific factors. In addition, it may be down to the logistics of availability, isolation procedures, banking and standardization, i.e. costs. Hope that helps.

  30. @Mahindra @Admin

    I am blunt in my comments and the topic is serious. That said, you guys still have not answered all the basic questions posed by me and others, and if these questions anger you guys, which clearly it did, I again couldnt care less. You consider my mere questioning as “low road”. Let me ask you this, would you enroll your children in this study?
    Your comments are again peripheral to the issue. If you will not allow anonymous comments, its simple, I will not post comments…so by all means do as you please. IF you are so offended by anyonymous comments, you should ask teh journals you publish in to reveal the reviewer names also…see the point?? Hope you do see the point.

    • Hi ALSadvocate,
      I’m not offended or angry about your comments. I was just reflecting on how I perceive them as unnecessarily hostile and negative. However, anonymous comments are accepted here as are angry comments as long as they conform to the comment policy overall. I realize there are a range of views and emotions, background, etc. at play in this arena.

  31. I review for many journals where the name of the reviewers and all their comments are public. I think this is fine, Why say something if you will not say it to their face. I think the only exception is when dealing with litigation bullies that drag people to court just to cost them money and to act as a chilling factor.

    I think in a serious complex discussion there are not ready made answers and that is why things are the way they are. Relationship changes perception over time and we learn from areas of mutual respect, willingness to change and a safe place to learn.

    A trial is not a treatment . It is a test of treatments, research is done to find out what works on who and to what extent. Treatment or intervention is using the modality tested in the trial for curative or stabilizing purposes. It sounds to me that you are wanting a clinical trial to be held to the same process as the clinical treatment and that is beyond the trials purpose.

  32. @ALSadvocate @Mahindra,

    If AlS wants more detailed information on what constitutes an ASE and AE and how this is differentiated for this study, what would be the process for ALS to contact the IRB or see the IRB document for specific information. It would surely be discussed in depth in the documents.

    The safety concerns are: “Even I, from the business world, can understand that this is not designed to measure the very same dangers that Ms.Kurtzberg herself expressed concerns about nor does it even touch the surface of the host of problems you mentioned above in your previous comment.”

    This seems a reasonable request, Professor Knoepfler could the PI be contacted by you perhaps to supply this information? We say we want patients and the public to understand risk, this is a perfect educational opportunity for all of us to discuss risk, find barriers to understanding and meeting needs of all stakeholders and to communicate together best ways forward

  33. @ Amy Price
    Look Ms.Amy….it is my personal preference about anonymity, a simple fact that if commenting is allowed as such, I opt for anonymity. Its nothing more complicated than a personal choice, and in return you can focus on substance rather than these irrelevant issues about who is behind the comments, which seem to take center stage with you guys and lead to some wildly imaginative thoughts…such as bullies, dragging people to court…etc.

    Let me give you an analogy for your “trial is not a treatment” comment. When a solicitor charges an individual with a crime, before the charges are brought the solicitor gathers all evidence and witnesses to convict the person of the crime should the case go to jury trial. So a solicitor first step of charging is based on solid evidence that will last him/her through the trial to get a conviction. In the Autism trial case, the charge is made with no evidence and there is no evidence that it will lead to a treatment and thus the case is utterly baseless. Can you argue otherwise?? You seem to think that it is justified if we could just stumble our way to a treatment by human experimentation, not based on solid evidence in the first place???

  34. @Paul,
    thank you for your answer, but I am wondering, why did they try their therapy at stroke patients? The only possible answer for me is that they may expect an improvement for these stroke patients. Of course, it is an phase I study. But nobody would do a phase I study, without the hope of a working new therapy.
    So I am wondering, could stem cells maybe help stoke patients?

  35. @ALSadvocate, I respect a personal preference for anonymity. I was stating it is no longer standard in journals, there are other models.

    In science solid evidence is determined by research and that includes clinical trials. These are what produce evidence. There is a free e book you can download on this http://www.testingtreatments.org/book/?nabe=4876413604724736:0

    Before a trial ever takes place if it is done properly all the existing peer reviewed evidence if there is any is quality assessed, graded and reviewed. There are many steps to doing a trial ethically.

    I treated your questions and concerns respectfully whether they were irrelevant or not to me because they were important to you. You never know what someone who has taken the the time to post or to respond to your post is going through. Bluntness is not a badge and it is a poor excuse for dispensing with courtesy. Kindness matters

  36. ALSadvocate,

    I think Paul, Amy, and Mahindra have been exceedingly patient with you. I, however, believe you at best to be a businessperson who did not care about ALS until you yourself or a close relative was diagnosed and at worst simply a troll.

    I am willing to assume the first, simply because that implies that maybe you can be reasoned with.

    I think you have adopted the tactic of simply yelling at people to “win” (whatever you think that means) and you are not willing to concede anything unless the other person unequivocally agrees your viewpoint is 100% correct. This is an incredible dangerous tactic to use in science as it stifles innovation, creativity, and in general civilized argument. To me, your use of this tactic along with the appeals to emotion that you’ve used, makes you unfit to use the pseudonym you’ve chosen at best, and at worst, a fantastic and compelling argument for excluding patients from having a voice at the table.

    Business tactics do not work in bioscience. People will eventually refuse to engage with you.

    Bioscience is also not criminal law. If those precepts were followed, clinical trials would almost never occur.

  37. @anonymous stem cell repairman
    When you come down from what ever you are high on, take a moment to read your post again and your comment handle, and then perhaps a look at yourself in the mirror.

    I raised legitimate concerns and for that I do not care to be nice to anyone, since this is a serious matter to me and it is better to lay it out straight as I feel it. You or anyone else are free to vigorously disagree with me, please make sure you post your arguments on the issue. Your wild analysis of me and my comments mean nothing to me nor do they address the issues.

    Tactics?? Really?? You think presenting my arguments on this blog now is some sort of a ‘business tactic’?

    Who is excluding patients from having a voice at the table? The only person who is moderating the comments here is Admin and Admin is free to exclude my comments if he/she feels they are out of line…simple as that.

  38. Yeah, I guess I was wrong. You’re most likely a troll. Your personal attack on me barely makes sense.

    You haven’t raised legitimate concerns and claiming that you have to excuse your bluntness is completely unreasonable. You started out by calling on Paul to denounce this as quackery, and then proceeded to demonstrate a complete lack (intentional or unintentional, it doesn’t really matter) of understanding and reading comprehension as others patiently explained how clinical trials worked. You continued to fail to demonstrate comprehension and continued to use a tone that is outright bullying. You have demonstrated that you are unwilling to be reasoned with. The way you present your arguments is certainly a tactic, it must have worked for you so far in real life.

    You totally failed to comprehend my statement about having a voice at the table.

    In the case you actually are an advocate for whatever reason: having your reality shattered by a disease that really has no approved or efficacious treatment is a terrible thing. To borrow Mahindra’s last response “Sorry I can’t offer you solace for the rest of your post but I wish you well and hope you can find some comfort in your quest.”

  39. @anonymous stem cell repairman

    I have no reason to attack you or your views. So you are very free to do as you please and explore your jumpy side with no provocation needed. For the sake of all, I hope you are not a stem cell researcher or a stem cell doc, and just entertaining yourself by your empty challenges. Its really funny and makes me laugh too. So keep going.

  40. Ignoring the hysterical troll,

    Paul, in your earlier response to Richie, you described the difficulty of making a convincing argument without an understanding of molecular/cellular underpinnings. I share this view, but playing devil’s advocate for bit: is this view shared by biotech in the gene and cell therapy field?

    With the retinal pigment epithelium stuff from Occata and Asterias, it’s pretty clear what the underpinnings are and how the proposed therapeutics work, but with stuff like Stem Cells Inc.’s neural cell therapy and the cord blood trial here it’s much less clear how the therapeutic cells even exert an effect, let alone what that actual effect is.

    How do we then reconcile the three interests of academic science/medicine, biotech, and the patients, particularly when one of those groups stands to lose more than the other two from lack of understanding?

  41. @anonymous stem cell repairman
    An often debated issue and “making a convincing argument [for a drug] without an understanding of molecular/cellular underpinnings” is not uncommon.

    The rationale needs to convince regulators, who will judge it at the level of expected safety and efficacy and benefit over existing therapies. For chronic, multifactorial diseases where a single mechanism is almost impossible to define (and good animal models may not exist) the rationale may be based on observations in other clinical studies.

    In the case of cord blood stem cells for autism, these cells have demonstrated anti-inflammatory activity and general support of regeneration in other trials and in preclinical study. What I think Paul was concerned about was that there is no evidence that such activities could ameliorate the pathologies of autism. I share this concern, but given that causative mechanisms for these pathologies have not been uncovered, we can only use our scientific knowledge and make a “best guess” and test these in controlled clinical trials.

    You cite Ocata’s RPE drug as having “clear” underpinnings, but AMD is a chronic, multifactorial illness and in some the causal lesion is photoreceptor degradation – what molecular underpinnings are there for transplanting RPE in this case?

    It is acceptable to test therapies for which no clear molecular mechanism has been described as long as the trials are designed according to principles of evidence-based medicine. The hope is that if the drug is successful, the molecular mechanisms will be delineated afterwards in order to improve on the drug and predict on/off-target effects.

  42. Mahindra,

    Thanks for info.

    By the “clear underpinnings” for the RPE drug, I meant for the dry form where the causal lesion is the RPE dying. Of course, the photoreceptors may start degrading as a result as well, so it may only halt progression. BioTime/Asterias has at least showed that transplanting RPE preserves vision in animal models. The transplantation should restore the normal interactions between the photoreceptors and the RPE, such as transport of retinal, nutrient and proper signaling, phagocytosis of shed membrane fragments, etc.

  43. @ anonymous stem cell repairman
    I agree, I was trying to point out that the molecular underpinnings and rationale for clinical testing may not always be as clear as one thinks.

    Ocata’s RPE drug is aimed to replace lost RPE in retinal dystrophies, including AMD and Stargardt’s disease. However, there are significant differences in the molecular pathologies of these diseases and some patients may have causative lesions that only indirectly affect RPE, such that, eventually, the transplanted RPE will also die. For patients who have lost both RPE and photoreceptors, one cannot expect any more than a slow down in disease progression at best as no new photoreceptors will be provided.

    So cord-blood cells for autism is a stretch on the molecular side, but is still a valid idea for testing. On the other hand, the apparently clear molecular underpinnings for Ocata’s RPE therapy are not as simple as one thinks, but this is also still valid.

  44. Having a child with autism, I can tell you, we HAVE fought inflammation in our child. And when you consider that only 5% of research dollars are spent on autism compared to other lesser prevalent childhood diseases, we are thrilled that someone of Dr. Kurtzbergs level of expertise is even willing to take this on. People don’t want to touch autism with a 10 foot pole because it is so hard to pin down. And how will we know what does and doesn’t work if we don’t’ get started. As these kids are getting their own stem cells, all the other issues such as rejection etc, don’t seem to come in to play. And because autism IS so different than most anything science has tackled, maybe we have to come at it in a different way than what is currently acceptable for research protocol. I spoke with the good Dr. years ago, begging her to do a trial when she was working on CP. Now my son is too old for the current trials – it was worth it for those behind us who will in some way benefit from this research. I would also encourage researchers to spend half a day with families that have a kid with autism in their home – all levels – from the “highest functioning” to those who wear helmets and have self and other injurious behaviors and all ages and stages. Take a month and visit one a day. Then you will see WHY ASD parents push hard on things that may help our family. Go to where the rubber meets the road. Then go back to your lab with a reason to get after it on our behalf.

  45. I completely agree with visiting with families who actually have autism. My son has autism and I have been in contact with many families who have used stem cell therapy. Some reported unbelievably gains. Don’t call it quackery unless you’re sure. That’s a very convenient word use to convey your point. Trouble is, we’re starting to see through this type of speech. It actually doesn’t have the intended effect. Much of what I have referred to as “quackery” is what has actually produced results. Perhaps it’s time for a paradigm shift.

Leave a Reply