Is a trial of stem cell therapy in autism scientifically and ethically justified?

Houston, we have a problem.

Oh, wait. I'm not talking about Stanislaw Burzynski this time. But we do still have a problem, and it's a problem that resembles the Burzynski problem I recently discussed. Specifically, it's a problem of unethical clinical trials somehow winning approval from institutional review boards (IRBs). In academia, IRBs are basically ethics boards whose purpose is to protect the human subjects who agree to take part in clinical trials and other research from harm and from being subjected to experimental therapies in which the risk-benefit ratio isn't sufficiently favorable. In other words, they are there to make sure that clinical trials are conducted with clinical equipoise. They have to approve clinical trials before they can begin and monitor them as they are performed, following up on adverse events and sometimes deciding to shut them down if there appears to be too much risk and/or harm. In the U.S., all institutions that receive federal funds (specifically, that have a Department of Health and Human Services-approved Federal Wide Assurance agreement) typically must agree to abide by the regulations governing human subjects research codified in what is known as the Common Rule. Similarly, any private entity (such as a pharmaceutical company) seeking FDA approval for its drug or device have to register with the FDA and abide by the Common Rule, whose most important set of rules mandate IRB approval and monitoring of the research. Some states also mandate that all human subjects research carried out within their borders, regardless of funding source, must abide by the Common Rule.

With all the laws, regulations, and rules that I have to abide by whenever I become involved in human subjects research, it never ceases to amaze me how some researchers can get away with the sorts of studies that they get away with. Think Mark and David Geier, who created a faux research institute and packed its IRB with their cronies to oversee their "studies" in which they subjected autistic children to chemical castration. Think Mary Holland. Think Stanislaw Burzynski. Think of all the other ethically dubious human subjects research that somehow manages to be approved and carried out in spite of laws and rules that, for those of us in academia, have become ever more onerous over the years.

Then ask yourself how this study could ever have been approved by any IRB, anywhere:

Families with autistic children must navigate a condition where questions outnumber the answers, and therapies remain sparse and largely ineffective. A clinical trial being conducted by the Sutter Neuroscience Institute in Sacramento, California to address this situation began recruiting participants today for a highly experimental stem cell therapy for autism. The institute plans to find 30 autistic children between ages 2 and 7 with cord blood banked at the privately-run Cord Blood Registry, located about 100 miles west of the institute.

I've written about stem cell quackery for autism many times. For instance, Kent Heckenlively hit his parents up for $15,000 to take his daughter to a highly dubious stem cell clinic in Costa Rica, where doctors injected "stem cells" (who knows what they really were) into her cerebrospinal fluid via a lumbar puncture. More recently, I noticed another autism "stem cell therapy" that was neither a therapy nor involved any actual stem cells and another child subjected to what are claimed to be stem cells by a quack clinic.

Is Sutter Neuroscience Institute another one? Certainly its website looks respectable enough, but then so do the websites of pretty much every dubious clinic offering unscientific therapies that I've ever seen. How spiffy a website appears tells us nothing, although the content of the website does give some clues, particularly the page Innovative medical and alternative therapies for autism spectrum disorders. There, you will find recommendations such as using vitamin C and vitamin B6 to treat autism, to "uncover food sensitivities" (which is a huge red flag for me), and to "try massage therapy" (which doesn't strike me as a particularly good idea for at least some autistic children, given the sensory issues so many of them have. To be fair, though, the Institute does state unequivocally that the scientific evidence does not support the claim that vaccines cause autism and that children should get all their childhood vaccines. The website also correctly points out that chelation is dangerous and doesn't work for autism; that facilitated communication also doesn't work; and that there is no convincing evidence for any supplements having a positive effect on autistic symptoms (which makes me wonder why the webpage I mentioned before recommended vitamin C and B6).

So why is this place, which seems (mostly) reasonable, sponsoring a clinical trial using stem cells to treat autism? The title of the clinical trial can be found easily on its website, and you know what I have to do whenever I see that. Yes, indeed, it's off to ClinicalTrials.gov, where I first found the precursor trial mentioned in the Scientific American article:

Already one other clinical trial, with 37 total participants between ages 3 and 12 years old, has been completed in China. The researchers affiliated with Beike Biotechnology in Shenzhen, the firm that sponsored the study, have not yet published any papers from that the trial, which used stem cells from donated cord blood. Mexican researchers are currently recruiting kids for yet another type of autism stem cell trial that will harvest cells from the participant’s fat tissue.

The Chinese trial can be found on ClinicalTrials.gov as well. Its rationale is:

Autism is one of those disorders in Autism spectrum disorders (ASD), which characterized by social interaction abnormalities, impaired verbal and non-verbal communication, and repetitive, obsessive behavior, while the therapeutic effect of current treatments remains limited progress. Neural hypoperfusion and immune deregulation are the two key pathologies associated with Autism. Human umbilical cord mesenchymal stem cells (hUC-MSCs) and human cord blood mononuclear cells (hCB-MNCs) have been shown to have the ability to modulate the immune response and enhance angiogenesis, suggesting the novel and promising therapeutic strategy. In this study, the safety and efficacy of hUC-MSCs and hCB-MNCs transplantation will be evaluated in patients with Autism.

This study was carried out overseas in china by a non-American company; so who knows what sort of ethics oversight it had. Its hypothesis is also dubious at best, but I'd rather discuss that in the context of the current clinical trial, whose ClinicalTrials.gov entry informs us:

Evaluate the efficacy of one infusion of stem cells from autologous umbilical cord blood in patients with autism over six months after infusion as measured by changes in expressive and receptive language.

Also demonstrate improved behavior, learning, and changes in Serum tumor necrosis factor alpha (TNF-α), tumor necrosis factor beta (TNF-β), interleukin 1-alpha (IL-1α), interleukin 1-beta (IL-1β), interleukin 6 (IL-6), interleukin 10 (IL-10), and interleukin 13 (IL-13).

Basically, this is a single-center, randomized, placebo-controlled, crossover outpatient study with 15 subjects. Subjects will receive one infusion of autologous umbilical cord blood (AUCB) containing stem cells or an infusion of placebo (saline). After the 24-week follow-up, the groups will cross over so that patients who initially received AUCB will receive placebo and patients who received placebo at baseline will receive the cord blood. Looking at it, right off the bat I wonder why the investigators consider it so important to do a crossover design. Then I realized. It's obvious. No parents would sign up for it if they didn't know that their children would get stem cells; so the Institute accommodated them.

So what's the problem with these studies? What why do I consider them to be unethical? It comes down to prior plausibility and preclinical evidence. According to the Helsinki Declaration, for a study to be ethical, there has to be solid preclinical evidence, in the form of in vitro and animal models, that strongly support the biological plausibility of the therapy proposed. What, I wonder, is the preclinical evidence supporting the use of autologous cord blood for autism? The introduction to the Chinese study tells us that the investigators are basing their rationale on the ability of human umbilical cord mesenchymal stem cells and mononuclear cells to "modulate the immune system." Specifically, these cells have been tested in some autoimmune diseases. In essence, they appear to slow down the immune system, inducing Treg expression and decreasing the activation of T cells. In essence, these cells are immunosuppressive.

Which brings us to the problem.

The rationale for using these cells is not that they're going to home to the brain and regenerate or repair parts of the brain in order to make them "normal" again. They are clearly being administered for their immunosuppressive/immunomodulatory activity, as evidenced by all the biomarkers being measured after their administration. They're all cytokines and other immune molecules. The investigators wouldn't measure all these cytokines if that's not what they were interested in. For this therapy to have a chance of working, there must be a major immune component that is causative of autism. Although a variety of immune changes and abnormalities have been reported in autistic children, thus far, none of them have been convincingly shown to be causative. They could well be an epiphenomenon. Certainly, the evidence for immune dysfunction in autism is not sufficiently strong to justify something as invasive as performing autologous stem cell infusions, particularly when it's not yet well understood what it is that autologous umbilical cord blood stem cells and monocytes do when reinfused.

Think of it this way: Do you think that the evidence implicating a hyperactive immune system is strong enough to justify treating autistic children with prednisone? Cyclosporine? Other immunosuppressive drugs? If not, then why would anyone advocate using autologous stem cells, which appear to be immunosuppressive? Why on earth would an institute like the Sutter Neuroscience Institute carry out such a trial based on low prior probability? What sort of preclinical evidence did they have to justify this trial? The scientists in the article who say that the likelihood of a positive result from this trial is low are, if anything, too optimistic. The likelihood of a positive result is almost homeopathically low. When it comes to clinical equipoise, this trial looks to me as though it's all risk with too little prospect of benefit to be justifiable without a lot more clinical evidence.

I really wonder what the IRB is that approved and is overseeing this trial.

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The scientists in the article who say that the likelihood of a positive result from this trial is low are, if anything, too optimistic. The likelihood of a positive result is almost homeopathically low.

Actually, given that they're looking at 11 different endpoints, the likelihood of at least one of them being "significant" at a 0.05 level is close to 43%. Of course, it's possible that they'd correct for multiple comparisons; it's also possible that Mitt Romney will realize that Paul Ryan is going to lose him more votes than he could gain.

I was also disturbed by the crossover design. Even if it worked (and like you, I know no reason to expect that it will), 6 months is an awfully short time to observe improvement in a developmental disorder, and the crossover design means there
Is no control group for long-term follow-up. After reading the study design, I figured that 6 months was the longest they thought they could convince parents to wait for the miracle treatment. But really, this is a study in which it would be better to be in the placebo group. No risk of potentially serious side effects (you can't very well uninject the cells if things go sour), and in the unlikely event that a big benefit in one group was seen, the code could be broken early and the treatment (if that was actually the group that benefitted) could be offered to all.

I hope this doesn't derail the thread, but a Bat-signal to Orac seems in order, given the press release from Strathclyde University announcing that

A compound found in green tea could be a weapon in treatments for tackling cancer, according to newly-published research at the University of Strathclyde.

-- the Daily Torygraph and the Daily Fail have both picked up on it so it will be all over the Wooniverse by tomorrow, if it isn't there already.

Details are scanty. There is talk of "intravenous administration", so it is not a purely in-vitro experiment; but the Torygraph journalist adds in addition that "a clinical trial in humans" is the ultimate objective", so clearly it has not been tried on humans so far. That report also specifies "human skin cancer", so if the the journalist hasn't made that up himself, the tests have been on xenografts.

The press release refers to a paper that can be tracked down to this one:
Antitumor activity of the tea polyphenol epigallocatechin-3-gallate encapsulated in targeted vesicles after intravenous administration, in a 'Nanomedicine' journal that's an imprint (if that is the word) of a purely on-line publishing house, "Future Medicine". I haven't come across it (nor has my university library). Even the *abstract* is pay-to-view, let alone the contents, which must remain an echidna wrapped in a carborundum.

By herr doktor bimler (not verified) on 22 Aug 2012 #permalink

@ebohlman

By "positive" I meant convincingly positive with respect to one of the primary behavioral endpoints, not according to all the secondary endpoints or correlative studies...

the Torygraph journalist adds in addition

I DID NOT WRITE THAT.

By herr doktor bimler (not verified) on 23 Aug 2012 #permalink

@HDB - didn't write the post? Were you spoofed?

Such an egregious solecism must have been inserted by the software. I blame Sepllchcek.

By herr doktor bimler (not verified) on 23 Aug 2012 #permalink

@ trrll quote = "I was also disturbed by the crossover design. Even if it worked (and like you, I know no reason to expect that it will), 6 months is an awfully short time to observe improvement in a developmental disorder, and the crossover design means there is no control group for long-term follow-up."

But surely this goes to the heart of the issue - without an established aetiology to measure against, and with no clear measures of what develomental changes leading to improved performance can be expected 'without intervention' - how could this study ever be meaningful ? Autism isn't a fixed condition, but one of developmental delay in which there is no established pattern of developmental progress, so how will this study account for improvements that may have occured without any intervention ?

By In Vitro Infidelium (not verified) on 23 Aug 2012 #permalink

@IVI - that's the "genius" of the study - they can claim any improvement in the child's condition will be a result of the stem cell therapy......that's what is called, "stacking the deck."

Methinks the herr doktor protests too much. :)

By Composer99 (not verified) on 23 Aug 2012 #permalink

People who have bizarre notions about the causation of ASDs ( which includes recent theoreticalising about immunology, courtesy of AoA, TMR et al) might feel that stem cells are the answer and agree to be subjects- i.e. SUBJECT their children to a trial.

Yesterday at TMR, Alison MacNeil contorted herself into knots about whether a 'treatment' is working or not and whether her son is a 'responder' or not. It appears that she might be trying several whimsy-based therapies simultaneously. I fear she's not alone.

Indeed, the Moms seem to be performing various supplement and dietary regimes and lord knows what else ( I shudder to think about it because I know what's out there, wafting in the breezes of woo-topia).

The woo-entranced are desperate in their quest to *recover*( I hate that malaprop with a passion) their children from autism. They might try anything.

In other news:
Jake reveals deeper under-pinnings that support the Grand Conspiracy @ AoA.
So does Mike Adams @ Natural News.
Must be the end of August.

By Denice Walter (not verified) on 23 Aug 2012 #permalink

@trrll

Yeah, the crossover design made me pause. They must be expecting it to work like a magic bullet. Give the stem cells and *BAM* the child's cured. Even if there was some plausible mechanism by which stem cells could work their wonder, I can't imagine it would be that fast.

I also noticed that this is listed as a Phase 2 trial, but I wasn't able to find their Phase 1 trial listed, unless they're just building off of that Chinese one, which strikes me as odd. The only other Phase 1 study I found was one using adipose-derived stem cells, from the Ageless Regenerative Institute.

Wait one second!

How will the anti-vaccine folks react to the realization that some stem cells come from embryos, if they're so quick to say that vaccines have aborted fetuses in them?

Anyway, like Todd wrote, where are the findings of the previous trials or animal models?

For a peek inside the various immunological ( and other) amateur theorising going on @ AoA: look at Theresa Conrick's musings especially.

By Denice Walter (not verified) on 23 Aug 2012 #permalink

What I find horrifying as an autistic person and a person who has tried this same drugs for psoriatic arthritis is that the subjects are so young and may not be able to communicate side effects very well.

Prednisone can be a miracle drug or EBUL! I had the worst side effects from prednisone, exhaustion, anger, chest pain, aches...it was worse than the arthritis.

How is a two or three year old going to handle that? I shut down and people had no idea I was suffering until I was moaning and breaking out in cold sweats.

There is so much wrong here, especially the cross over, that all I can think is that this is a publicity stunt to drum up bidness.

As others have pointed out, autism is characterizwed by developmental delay not developmental stasis. Even if stem cell infusions could prove effiective at treating autism, as designed this study won't allow improvements due to infusion to be detected. With no blinded control group that receives no stem cell infusion whatsoever, there's no way to distinguish between improvements actually due to infusion and improvements that expected to occur in teh absence of any treatment as a conwequence of normal developmental change in untreated ASD subjects.

Even if this study passed the ethical bar, there'd still be no reason to perform it as designed--and as it is, it's batting zero for two...

@ Liz
Fecal transplant? How is that supposed to be done?

@ Ren: I think these kids will be receiving their own stem cells from their cord blood. The cord blood storage business is described as being 100 miles north of Sacramento where the clinic is located and the parents paid for the original collection/frozen storage at the time of birth, plus yearly frozen storage fees.

@ Anne: Nice links. Michael G. Chez did at one time practice in Illinois under license number 036074985 and then did not renew his license; there were no disciplinary actions listed for him when he practiced in Illinois. His license in California is current...with no disciplinary actions on his record. Your link from the appeals court in Illinois showed that the case was remanded back to the lower court...judicial error in not permitting the plaintiff's expert witnesses to give testimony, which resulted in the dismissal of the case against the doctor. Has anyone found a link to the lower court...and possibly a verdict against the doctor...or did they settle out-of-court, once the case was remanded for retrial?

The expert witnesses are doctors who stated that Dr. Chez rather abruptly withdrew cortisone, instead of tapering the medication. Chez instructed the parents to put their child on so-called "pulse" therapy (on and off the cortisone)...which resulted in adrenal failure, according to the expert witnesses.

IRB = IRB00001813 - Sutter Hlth Central IRB #1

Clinicaltrials.gov identifies Sutter Institute for Medical Research, which I entered in the OHRP database: http://ohrp.cit.nih.gov/search/fwasearch.aspx?styp=bsc

Apparently clinical equipoise is out the window as it was when IRBs approved the Trial to Assess Chelation Therapy.

By Agrippina (not verified) on 23 Aug 2012 #permalink

@ Renate: Fecal transplants are being done to recolonize the bowels of people, who from infections or through certain medical treatments, are unable to digest food:

http://www.sciencebasedmedicine.org/index.php/the-species-in-the-feces/

There are quite a few comments on autism boards for parents who want to attempt a do-it-yourself fecal transplant to *cure/recover* their autistic child.

"it’s also possible that Mitt Romney will realize that Paul Ryan is going to lose him more votes than he could gain"

I'd prefer not to read completely irrelevant partisan comments here, especially the first fricken comment. I come here to get away from all that. Off-topic provocative comments can be considered trolling.

By Ultra Venia (not verified) on 23 Aug 2012 #permalink

@Denice Walter

Yesterday at TMR, Alison MacNeil contorted herself into knots about whether a ‘treatment’ is working or not and whether her son is a ‘responder’ or not. It appears that she might be trying several whimsy-based therapies simultaneously.

As I recall, MacNeil recently disclosed that following a couple of years of chelating her son regularly (waking him during the night to dose him, etc.) she recently changed to a homeopathic approach. Accordingly, you might consider which of these is least likely:

(1) administering highly-purified water diluted in highly-purified water is an effective treatment for ASD
(2) given that the great majority of children with ASD improve with time in language and social skills (and roughly one in ten make such significant improvements that they move from the most impaired range to the highest-functioning range) [Pediatrics. 2012 May;129(5):e1112-20]; MacNeil's son is improving as might be expected with or without homeopathy, etc.
(3) discontinuing unproven and potentially harmful therapies including repeatedly waking the child to chelate him in the middle of the night for years may have helped him to improve.

In other news:
Jake reveals deeper under-pinnings that support the Grand Conspiracy @ AoA.
So does Mike Adams @ Natural News.
Must be the end of August.

The clock is ticking for the Wakefield appeal to be filed.

lilady:

The expert witnesses are doctors who stated that Dr. Chez rather abruptly withdrew cortisone, instead of tapering the medication. Chez instructed the parents to put their child on so-called “pulse” therapy (on and off the cortisone)…which resulted in adrenal failure, according to the expert witnesses.

Good lord! He gave the kid Addison's Disease and he got off scot-free? Astounding. If he'd done that to my kid, there would probably be a second court case -- against me, for assault. I had a relative who lived with Addison's for many years, and my mother's dog has recently developed it as well. It's really not a fun disease to have. I'm still amazed that my grandmother has managed to avoid it, what with all of the prednisone she's taken over the years for her severe asthma. (She does have many other chronic health conditions resulting from long-term prednisone use. For instance, her skin is so fragile that when a well-meaning ER doctor gave her a band-aid once, she ended up needing a skin graft. About the only thing she can use for cuts -- and she gets a LOT of cuts -- is gauze and Steri-Strips.)

By Calli Arcale (not verified) on 23 Aug 2012 #permalink

On this sidetrack, I'll offer a prediction: Wakefield will file a motion for a new trial prior to September 3, which will give him an extra 60 days to file an actual notice of appeal.

I am constantly amazed at the lack of clinical trial oversight by the regulatory authorities. When you compare the strict regimes that accompany pre-clinical testing and the manufacture and testing of drugs and medical devices, the oversight and regulation of clinical trials is almost non- existent. Certainly this behaviour would never be allowed with an animal study.

in more important news Blakes 7 to be re-made by the sci- fi channel
http://www.deadline.com/2012/08/syfy-to-develop-remake-of-cult-u-k-sci-…

Ignore me, I don't think that will work upon further reflection.

Agree with Orac about the motivation for using a crossover trial. But I'd go farther and say that with such a short crossover time, in the context of a condition in which spontaneous improvement is the norm, this was a deliberately chosen strategy to exaggerate benefits. Combined with their choice of immune-related outcome markers, they're as much as declaring that they intend to make some unsupported conclusions.

I'd also point out that as advertised, the stem cells are supposed to offer permanent benefit, so the choice of a crossover trial is bizarre. Unless they aren't... maybe the investigators want to show the marks that they need to buy treatments on a regular basis?

@ brian:

It sounds as though she's been trying out different 'bio-med' approaches for the past 5 years, including supplements, homeopathy and dietary approaches, sometimes more than one at a time ( see yesterday's post and one in June, entitled 'Top 20 Healing Ideas')
as he is "alive but not exactly living", she appears to be buckling down to her 'work'.
If you look on facebook pages, you'll discover that TMR is liked by thousands.

By Denice Walter (not verified) on 23 Aug 2012 #permalink

@ Narad:

I expect that AJW will cobble together a pastiche of legal bloviation before Sept IF he still has free legal aid courtesy of Parrish and others.

Then Jake *et les autres* get to glue together their own reactions to said cobbled together legal nonsense *ad infinitum*

THEN, they'l hold a benefit dinner/dance or suchlike.

By Denice Walter (not verified) on 23 Aug 2012 #permalink

There are two things I'd like to comment on.

1. Sutter Neuro is part of a regional healthcare network, and it really surprises me that they are jumping with both feet into woo. Various people have suggested that I try their clinic for more pedestrian interventions, such as occupational therapy, though it is far enough away it would cost me around $200 in gas and lodging per trip. However, after learning of this unethical "study," I don't think I want anything to do with them. I'm glad my procrastination saved me from getting involved!

2. Steroids to treat autism? Isn't the main medical issue cited to prevent Paul Corby from getting a heart transplant that his doctors are afraid the steroids for post-transplant care will exacerbate his mood/behavior issues? (Anecdotally, prednisone makes me feel very very weird, not myself and not in a good way, and enough that others around me ask what's wrong.)

Renate, the "do it yourself" autism parents who are willing to perform mad-scientist experiments on their victims -- I mean children -- have been sharing "home" fecal transplants protocols on listserve discussions for a few years. It's almost as bad as the bleach enemas. Now Bradstreet is telling parents how to do it.

Kathryn, if you are in the Valley of the Heart's Delight I'm thinking of -- you know, the one where the capital city is named for St. Joseph -- I can recommend to you several excellent OTs closer to home.

I dunno, Orac. I see more biological plausability than you do, maybe.

Did you read:
J Transl Med. 2007 Jun 27;5:30.
"Stem cell therapy for autism."?

"Cord blood CD34+ cells are known to be potent angiogenic stimulators, having demonstrated positive effects in not only peripheral ischemia, but also in models of cerebral ischemia. Additionally, anecdotal clinical cases have reported responses in autistic children receiving cord blood CD34+ cells. We propose the combined use of MSC [mesenchymal stem cells] and cord blood CD34+cells may be useful in the treatment of autism."

It's a very broad approach, combating "immune dysregulation" with stem cells of different lineages, but I don't know if I agree it's some sort of generalized immunosuppressant. I might call it adding normal feedstock, like giving probiotics to someone with a H. pylori stomach infection. If that's the goal (combating immune dysregulation), I assume they are monitoring cytokines to determine engraftment and development.

By c0nc0rdance (not verified) on 23 Aug 2012 #permalink

@ Liz
Are those people administiring the fecal transplant orally or anal? I think those people are raving mad, but well, that's my humble opinion.

Thanks for the info lilady. It sounds disgusting. Glad I've already had breakfast. Don't know what is worse, bleach enema's, or this. It doesn't matter, both are so far off, it's hard to imagine any parent in the right mind would subject it's child to something like those.

Some random thoughts.

Fecal transplant is a legitimate, though last-ditch, treatment for C. Diff.

I'm concerned that legitimate stem cell research is going to get buried under quackery and become less attractive to researchers.

Could the fat extracted during liposuction be used as a source of stem cells? If so, there's gold in them there adipose deposits.

By Krebiozen (not verified) on 24 Aug 2012 #permalink

I actually referred Renate to this SBM article on fecal transplants upthread:

http://www.sciencebasedmedicine.org/index.php/the-species-in-the-feces/

Yeah, it might be *odd* to contemplate undergoing this procedure, but it is far better to try it, than to contemplate a life of TPN (total parenteral nutrition). The interesting thing is that the best *donor* is a household member, even if the donor is not related to you.

Additionally, anecdotal clinical cases have reported responses in autistic children receiving cord blood CD34+ cells.

(Bolded for emphasis.)

The plural of anecdote, even when amplified by the phrase "clinical cases", does not share identity with evidence.

If we were to provisionally accept that there is an inflammatory component to autistic disorders, such that modulating immune response would be beneficial, stem cell infusion would logically represent the final step of a series of clinical trials rather than the opening round. There are a number of established, less invasive approaches to modulate immune response in order demonstrate proof of concept than infusing autologous stem cells. These approaches are also reversible, while infusion is not: as others have pointed out once infused the stem cells are potentially active forever, while small molecule or biologic immunomodulaters like prednisone, rapamycin, Humira, etc. have relatively short half-lifes.

There's the larger the problem with this study that in the absence of a true control group--one which receives no stem cell infusion over the entire duration of the study--there's no way to assess whether any perceived developmental improvement is a function of stem cell infusion rather than simply representing the normal but delayed development common to autism spectrum disorders: even if stem cells do work this study won't provide evidence of that fact.

If Sutter Neuroscience really believe immunomodulation will be beneficial, they need to do all the tedious, hard preliminary trials first, to establishproof of concept rahter than jumping on "anecdotal" clinical evidence and leaping in to human clinical trials involving stem cell infusion. And of course, once reaching the stage where it's reasonable to proceed further and look at stem cell infusion design an appropriately controlled study that will actually answer the questions asked. Theya ren't there yet.

Lilady, I have the impression I overlooked that link. Still it sounds a bit yuckie to me and even if a fecestransplant is good in some extreme cases, it doesn't sound like it's something to do with an autistic child, just like chellation.

@JGC
I was all prepared to defend the biological plausibility of treating autism as cerebral ischemia with stems cells known to be angiogenic and immunomodulatory, but in my background research, I find that there is absolutely no evidence to suggest that ischemia is linked to autism spectrum disorders.

I must therefore, do something never before attempted on the Internet:
Admit I was wrong.

Valid points, JGC. Thanks for calling me on it.

By c0nc0rdance (not verified) on 25 Aug 2012 #permalink

This is ridiculous. For years I have been hearing "adult stem cells need to be subject to clinical trials before being accepted as a legitimate treatment". And now, finally, a man has the chutzpah to begin a clinical trial for autism using a patient's own cord blood. And what happens? The same people start whining that the clinical trial isn't good enough and has flaws. Every clinical trial has flaws. That is the reason every single research paper ends with "these results are promising, but more clinical investigations are needed....etc." A certain English major graduate named Doug Sipp masquerading as a Bioethics director and others like him just make my skin crawl. Nobody complains when Duke University does a "clinical study" for the past 5 years with seemingly no oversight using the exact same cord blood stem cells, but when somebody else tries to do it- it is flawed.

By Don Margolis (not verified) on 28 Aug 2012 #permalink

@ Don:

Did you actually read the post? Not only could this "study" not provide any actual results (by design), it's grossly unethical for subjecting vulnerable children to risks without any foundation to believe they might possibly be helped.

Yes stem cell treatments need to be studied. That is not the same thing as saying that any random BS involving them should be considered a legitimate and appropriate study!

Which Duke University study are you referring to, Don? For what illness, using what design? What evidence suggests the study is being conducted without appropriate oversight? The devil, as always, is in the details.

A trial designed Sutter Neuroscience's is--lacking a true control group and unable to distinguish between developmental improvements which may be due to treatment and changes that simply represent normal but delayed development characteristic of autism specturm disorders--does no one a service, neither those seeking support for additional stem cell trials in general nor those seeking an effective treatments for ASD's.

" A certain English major graduate named Doug Sipp masquerading as a Bioethics director and others like him just make my skin crawl."

Gee Don, I don't know why you suffer from pruritis, just because Don Sipp has blogged multiple times about you, your business plan/colleagues and your stem cell enterprise

http://sctmonitor.blogspot.com/#uds-search-results

A certain English major graduate named Doug Sipp masquerading as a Bioethics director and others like him just make my skin crawl

That's pretty funny coming from a business major masquerading as a medical expert.

I’m talking about this study at Duke

So I surmised. Why, then, do you characterize it as having been going on "for the past 5 years with seemingly no oversight" when only started two years ago?

You know what's not funny, Don?
Posing as a medical expert in order to drive innocent patients into an ineffectual treatment from which you benefit financially.
I'm not laughing.

And sorry lilady, the only pruritus I have is for women in Thailand.

Are you sure you don't mean "from"? Say hi to Patpong.

For Narad- the stories of Dallas Hextell and Chloe Levine are well documented over the internet. There were many others. They were treated at Duke in 2008. Only now is Duke claiming a "clinical trial" .

And Adam- please turn that frown upside down. There are many physical and mental benefits of laughing. And if that English major Doug Sipp can comment on stem cell treatment, why can't I? I haven't said that I am a medical expert and to the best of my knowledge, I don't think Doug has said that either.

By Don Margolis (not verified) on 28 Aug 2012 #permalink

For Narad- the stories of Dallas Hextell and Chloe Levine are well documented over the internet.

Oh, I see, you were referring to a different trial than the one you cited. Gotcha.

There were many others.

Looks like one shy of a baker's dozen. Do you have a point here?

Good day Narad,

Yes, my point is that there really was no "clinical trial" at Duke. They just started treating patients using the patient's own cord blood. (If you can find a clinical trial they based this current trial on, please kindly point it out). Oddly, there has been no outcry about this, most likely because it is a prestigious University. However, when Sutter (obviously lacking the name recognition of Duke) decides to do something very similar, we are now seeing many complaints.

By Don Margolis (not verified) on 29 Aug 2012 #permalink

First let me say that Margolis is a well known snake oil salesman and Guano crazy troll on any stem cells thread. Don Margolis has attempted to use the children's stories out of Duke from the CP/ cord blood study for his own slimy purposes. Margolis has been called out on it by Duke and the parents for it, to the extent that parents have a google alert on him and the second he even mentions the children by name, the parents contact the legal dept. at Duke. I should know, my child was one of the very first to go to Duke in 2005 and I've hated Margolis since then. So, be on the look out for more of those cease and desist papers Don.

That said, the children that received their autologous CB/CP transplant before the Phase 2 at Duke (found here http://clinicaltrials.gov/ct2/show/NCT01147653?term=cord+blood+cerebral… ), were in a safety trial that had all the I's dotted and T's crossed. The current study at Sutter is being funded by CBR cord blood bank, is only accepting patients with cord blood banked at CBR, and is probably able to move forward because translational safety trials have already been conducted. I wish more children were eligible from other cord blood banks to participate, and the dark side of this is one company will be able to exploit this as a personal marketing tool if it produces positive outcomes.

well documented over the internet.

Just repeating those five words so I can sit and stare at them for a while.

By herr doktor bimler (not verified) on 29 Aug 2012 #permalink

@ Don Margolis:

"And sorry lilady, the only pruritus I have is for women in Thailand."

Are you human trafficking now, Don?

"For Narad- the stories of Dallas Hextell and Chloe Levine are well documented over the internet."

This is the "testimonial" about Chloe Levine via YouTube:

http://www.youtube.com/watch?v=ws7M6lihWlM

Notice according to her parents, CT scan revealed that Chloe had a section of her brain that was "undeveloped" and possibly had experienced a small brain bleed. Once she had her own cord blood stem cell transplant, she was using her hand within a week of the treatment and there was a dramatic increase in expressive language skills.

Where is the result of the post-stem cell treatment CT scan...to show us that the undeveloped brain tissue was repaired?

It's a miracle...I tell you...simply a miracle!!!

The children that received their autologous CB transplant before the Phase 2 CP trial at Duke (found here http://clinicaltrials.gov/ct2/show/NCT01147653?term=cord+blood+cerebral… ), were in a safety trial that had all the I’s dotted and T’s crossed. My son was a first in the safety trial at Duke in 2005. As a parent, I knew I could not be objective, and did what I could to provide a clearer picture through a baseline I set up with his physicians and therapists before the transplant and then with the same in follow up which I shared with Duke. My thought was if there was a change, it could be gauged and promote interest. I was instrumental in raising the 10.2 million for the Phase 2 and have never called this a miracle, although others have. http://www.c-spanvideo.org/videoLibrary/clip.php?appid=595672315

The current study at Sutter is being funded by CBR cord blood bank, and is only accepting patients with cord blood banked at CBR. It is able to move forward because translational safety trials have already been conducted at Duke. I only wish more children were eligible to participate in the Sutter study from other cord blood banks.

Duke has nothing to do with Don Margolis and he has been warned repeatedly by the legal dept. at Duke to not use the children to validated his snake oil business.

By Mary Schneider (not verified) on 29 Aug 2012 #permalink

Hi Lilady, Are you saying you don't believe the parents of Chloe Levine?

And to Super and Mary- can anyone please show me the published research of this safety trial that began in 2005 with all the I's dotted and the T's crossed?

By Don Margolis (not verified) on 30 Aug 2012 #permalink

@ Don Margolis: You've already been busted, as being a scam artist and a snake oil salesman, preying on credulous parents who want to *cure* their autistic children. Now, just ago away.

Don, why don't you show us evidence that your trial is legitimate before you demand disproof of your allegation that Duke's wasn't? Without it, all your claims are merely examples of the tu quoque fallacy.

By Antaeus Feldspar (not verified) on 30 Aug 2012 #permalink

For Narad- the stories of Dallas Hextell and Chloe Levine are well documented over the internet. There were many others. They were treated at Duke in 2008. Only now is Duke claiming a “clinical trial” .

The Duke pilot study (according to the news source), found with a simple Google search (Duke University cerebral palsy cord blood) [the "cord blood" was from the autocomplete function, btw]

Cord Blood for Neonatal Hypoxic-ischemic Encephalopathy

Study Start Date:January 2008

By W. Kevin Vicklund (not verified) on 30 Aug 2012 #permalink

Thank you W. Kevin. I appreciate your efforts in trying to answer my question.
However, this trial is only for infants 14 days of age and under and it doesn't seem to be completed yet. Chloe Levine was 2 when treated and Dallas Hextell was around the age of 2 as well. And Mary above states her child was treated in 2005 and this trial began in 2008.

On Dallas Hextell:

http://today.msnbc.msn.com/id/23572206/ns/today-today_health/t/amazing-…

I particularly like this quote from that article:

"Although Dallas’ case was not part of a controlled case study, Snyderman said it should not be overlooked in the progressing studies of stem cell treatments.
“I think the thing that medicine has not done very well is we haven’t made a big enough deal about anecdotes,” she said. “This is not a controlled case study. It’s not a randomized clinical trial. But it is a child with a diagnosis who got a transfusion of stem cells and not only stopped the deterioration of his problems, [but] he’s doing better."

I'm not against Duke treating patients - in fact, I think it is wonderful. If Duke had played by the rules, families like the Hextell's and Levine's wouldn't have had their children improve so notably.

And for Lilady, the adult stem cells are never a cure, but a treatment to help improve the patient's quality of life. 2 good examples are Dallas Hextell and Chloe Levine. That is reason to rejoice :)

By Don Margolis (not verified) on 30 Aug 2012 #permalink

Here's an article with quotations from a stem cell researcher who participates in the Duke stem cell studies. She states that the *miraculous* cures being shown on the internet as occurring within 5 days are bogus. So too, are the claims of parents who state their child was not walking before the procedure, according to this stem cell researcher:

http://cpirf.org/wp-content/uploads/annals-of-neurology.pdf

Don, you never answered lilady's regarding actual evidence in the form of a post stem cell treatment CT scan demonstrating Chloe's damaged/undeveloped brain tissue had in fact recovered.

If there is no such evidence that the stem cells actually repaired the known damage, how is your insistence "She got stem cells and then improved?" any different from an anti-vaxer's insistence "He got vaccinated and was diagnosed with autism"?

Surely you've got something other than sequence of events to hang your argument on (or does your position really reduce to "what else could it have been?")

(or does your position really reduce to “what else could it have been?”)

I really don't know what the hell his position is supposed to be other than viewing cord-blood studies are some sort of inexpensive marketing opportunity for what he himself is hawking. He seems to be alternately pissed off about the Duke work ("nobody complains when Duke University does a 'clinical study' for the past 5 years with seemingly no oversight"; what are the scare quotes for?) and to defend it.

Searching for "Margolis Zannos Grekos" certainly dredges up a spectacular history of sleaze. It is worth repeating the search regularly, if only to encourage the Google algorithm to keep Margolis' business affairs fresh in its collective memory.

If only the Internet could be scrubbed clean!

According to RSCI Chairman Don Margolis, "Dr. Grekos is taking his groundbreaking work in regenerative biomedical technology to an international arena that has never before seen the dramatic clinical success achieved with his end-stage disease patients. RSCI is proud to have Dr. Grekos on its advisory board and there isn't a company or an institute in the world with the Repair Stem Cell treatment skills and experience that he and its other members bring."

By herr doktor bimler (not verified) on 30 Aug 2012 #permalink

“This is not a controlled case study. It’s not a randomized clinical trial."

Do you know what the words "controlled" and "randomized" mean, Don? They're not there just to add syllables and look pretty. "not a controlled case study" does not equal "not a case study." "not a randomized clinical trial" does not equal "not a clinical trial." Nothing you've shown so far justifies your claim that Duke is not "playing by the rules"; even if you actually managed to support that claim, it would only be a tu quoque argument; it would not give you the permission you appear to be craving to not play by the rules.

By Antaeus Feldspar (not verified) on 30 Aug 2012 #permalink

Searching for "Don Margolis" + "Lawrence Stowe" or "Frank Morales" also brings up some dubious business associations.

By herr doktor bimler (not verified) on 30 Aug 2012 #permalink

Ok, that is fine. If Duke did complete a clinical study demonstrating the safety of implanting a child's own cord blood stem cells- that is great, I will be ecstatic. I simply asked (not demand) to see the research and nobody has been able to show me.
If Duke did not conduct a trial for safety, then I kindly ask why they are beginning a Phase 2 study themselves . And I ask why there aren't similar blog posts like this one talking about the dangerous risks of implantation of one's own stem cells at Duke. There would seem to be a double standard.
I have no problems with Duke implanting a child's own cord blood, I think it is safe and can help the children. My thoughts are the same for the Sutter children as well. Though Mary does not like me, I agree with her above comments.

By Don Margolis (not verified) on 31 Aug 2012 #permalink

No more snide remarks on the dangerous risks of children receiving their own stem cells? Good for the Duke children and Sutter children.

Here is more on the Doug Sipp scam . He has no bioethics training and was an English major , and ex-trucking supervisor http://www.sctmonitored.blogspot.com/

By Don Margolis (not verified) on 12 Sep 2012 #permalink

Way to creep out the woodwork, Patpong.

Don't disparage Don's patpong sewer, Narad...that locale is where he enlists people for his IRB.

When it comes to autism performing a research is better than sitting and and always debating its ethics. Those who understand autism now that we are not talking abouts Einsteins...there are many nonverbal, selfinjurious who cant communicate. To help this children if this stem cells can help and reduce inflammation markers its already a start. It could have a real impact since brain inflammation has been consistently being demonstrated in major clinical studies.

When it comes to autism performing a research is better than sitting and and always debating its ethics. Those who understand autism now that we are not talking abouts Einsteins...there are many nonverbal, selfinjurious who cant communicate. To help this children if this stem cells can help and reduce inflammation markers its already a start. It could have a real impact since brain inflammation has been consistently being demonstrated in major clinical studies.

When it comes to autism performing a research is better than sitting and and always debating its ethics. Those who understand autism now that we are not talking abouts Einsteins...there are many nonverbal, selfinjurious who cant communicate. To help this children if this stem cells can help and reduce inflammation markers its already a start. It could have a real impact since brain inflammation has been consistently being demonstrated in major clinical studies.

When it comes to autism performing a research is better than sitting and and always debating its ethics. Those who understand autism now that we are not talking abouts Einsteins...there are many nonverbal, selfinjurious who cant communicate. To help this children if this stem cells can help and reduce inflammation markers its already a start. It could have a real impact since brain inflammation has been consistently being demonstrated in major clinical studies.

When it comes to autism performing a research is better than sitting and and always debating its ethics.

That's like saying "It's always better to pull the trigger and fire a bullet than to aim and make sure you're aiming at the correct target."

Those who understand autism now that we are not talking abouts Einsteins…

Oh, and only "Einsteins" are worthy of being protected from ethically dubious experiments? Does that apply to you, too? Somehow I doubt you're an "Einstein"; does that mean we can experiment on you?

there are many nonverbal, selfinjurious who cant communicate. To help this children if this stem cells can help and reduce inflammation markers its already a start. It could have a real impact since brain inflammation has been consistently being demonstrated in major clinical studies.

Nothing you have to say here supports the idea that it's okay to cut ethical corners in doing these studies.

By Antaeus Feldspar (not verified) on 17 Oct 2012 #permalink

The autism epidemic can not sit and wait for the perfect clinical design. Parents of severly autistic children have come to realize that the outcome for their children with no intervention, is far worst than the potential harm done by an unethical clinical trial. Risk vs benefit is all realitve to perspective. As a parent of a child with ASD, I see the potential benefit of having language, communication and a future, far outweighing the potential risk from a stemcell transplant. Afterall, we are talking about stemcell transplant, a treatment that has been widely used for cancer patients for over a decade.