Apr 06 2010

Bad Reporting about Stem Cell Treatments for Stroke

Michele Mandel, writing for CNews (a Canadian outlet) is responsible for one of the worst examples of science and health news reporting I have ever seen. Certainly she is at the top of my list so far for the worst reporting of the year.

She tells the story of Alda Byers, a 52 year old woman who suffered a brainstem stroke and is now locked-in – a syndrome in which she is conscious but mostly paralyzed and can only blink her eyes. This is a devastating neurological condition, and I fully understand the desperation of her family in seeking a cure. Unfortunately, currently there isn’t one.

But we are living in the golden age of quackery, where a global market of false hope is peddled over the internet. And so Byers’ family found a stem cell clinic in Mexico willing to treat her stroke with a stem cell transplantation. Mandel does not name this mystery clinic in Mexico, or the doctor who runs it or who treated Byers. We learn no details about the treatment except that it was “stem cells.”

The story is actually fairly predictable from that point – the family raised the money necessary to take Byers to Mexico and receive the treatment (we are not told how much it cost but these clinics typically charge tens of thousands of dollars). After receiving the treatment the family was convinced that Byers improved, reporting that she could move her head from side to side, form her mouth into an “o”, and wiggle her toes. But the improvement was not sustained.

Then we get to the focus of Mandel’s story – in order to continue the treatment Byers needs a Canadian doctor to prescribe a cocktail of drugs (erythropoeitin, filgastrim and somatotropin), but the family cannot find a doctor willing to prescribe them. Here we have the human interest story that Mandel wanted to tell, regardless of the facts or the dictates of journalistic integrity. She concludes:

And as she watches him, her blue eyes spill unspoken words of unbearable defeat. It’s as if someone dangled the key of hope before her and then cruelly snatched it away.

Leaving her locked-in for good.

I do not want to in any way minimize the sincere plight of Byers and her family. I have treated patients who were locked-in and it is one of the worst neurological conditions we face. My problem is with Mandel’s framing of this story as cruel doctors snatching hope from a desperate patient. This is utter rubbish. Mandel does not interview a doctor and provide any explanation for why they would refuse to prescribe these drugs. She does quote Byers’ husband, who can only speculate:

“There was definite improvement here. Why someone wouldn’t want that to continue is beyond me,” insists Byers. “I guess they’re all afraid of malpractice suits.”

I suspect there is another explanation – the doctors understand that this treatment is bogus and that Byers is being exploited by a con-artist in a white coat. Facilitating such exploitation raises serious ethical issues, and is not in the patient’s best interest.

That is the story behind the story, but apparently Mandel was not interesting in such things, or even a pretense of false balance.

Stem Cells for Stroke

What is the current status of research into stem cell therapies for stroke? At present we are at the animal research level, mainly producing strokes in rats and then transplanting various types of stem cells with various techniques and following outcomes. Early results are encouraging, but we do not yet have sufficient data to transition to human trials, although we may be getting close. There are many questions to be answered: what are the stem cells doing exactly, do they survive and form connections, do they support native cells in their recovery, do they limit inflammation, and what are the long term outcomes?  A recent review of the research concluded:

Future studies of neuroregeneration will require the demonstration of function in endogenously born neurons following focal ischemia. Further, methods are currently lacking to demonstrate definitively the therapeutic effect of newly introduced neural cells. Increased plasticity following stroke may facilitate the functional integration of new neurons, but the loss of appropriate guidance cues and supporting architecture in the infarct cavity will likely impede the restoration of lost circuitry. Thus careful investigation of the mechanisms underlying trophic benefits will be essential. Evidence to date suggests that continued development of stem cell therapies may ultimately lead to viable treatment options for ischemic brain injury.

Translation – cautious optimism, but we are not there yet.I would also point out that much of this research involves transplanting stem cells shortly after the stroke, and so some of the improvement may be due to a protective mechanism (limiting damage) rather than a restorative function (growing new brain cells). This would therefore not translate into treatment long after a stroke (more than a few days).

So why is it that an anonymous clinic in Cancun Mexico would be years ahead of leading research centers in translating stem cell therapies for stroke in humans? The simplest answer is – they aren’t.

Further, if this Mexican clinic had a new treatment that was more effective than what leading researchers were so far able to develop – where is their published research? Why aren’t they telling the medical community about their breakthroughs, and doing the kind of clinical trials that would convince doctors their treatments work? There is absolutely no legitimate reason not to do this. If they were transparent and were doing ethical research and had a treatment that worked, their clinic would become world famous and they would have more clients than they could deal with. Their techniques would also spread to other centers and the research would be expanded. That is what happens when a treatment is legitimate.

What about Byers’ story – did she really improve? We don’t know, because there does not appear to be any scientific follow up of her condition. In stroke trials patients often appear to improve even with placebo treatments. There is what is known as the “cheerleader effect” – tell someone you have given them a treatment and encourage them to do more, and they will do more – if for no other reason than perhaps they are trying for the first time in a while. That is sufficient to explain this story, at least in the absence of objective stroke scales documenting maximal neurological function prior to treatment.

Further, it is quite possible that Byers was given one or more drugs that may have treated a post-stroke depression or temporarily stimulated neurological function, or she was given some intensive rehab – giving the appearance of a temporary minimal improvement, but just enough to stoke the fires of hope and make the treatment seem legitimate.

It is also possible that the clinic actually transplanted neural stem cells (we cannot take this for granted, but it’s possible) and that they provided a temporary benefit to brain function. This is plausible given existing research. But one of the big questions and challenges is – how long do such cells survive? Patients may be better at 30 days, but not 6 months. This is a common problem of both fetal and stem cells transplants, and is one of the technical issues researchers are working on.

If in the very unlikely situation that these Mexican doctors actually have an effective stem cell treatment, then they are guilty of extreme malfeasance. By failing to do ethical, transparent, and scientific trials of their treatments they are depriving their patients of proper follow up (as is evidenced by the Byers case) and the world of their treatment. This is unethical in the extreme.

But it is more likely in my opinion that they are just charlatans.

The press needs to do a far better job of exposing these exploitative clinics to the public – they are there to take large sums of money from desperate patients and their families and friends. Their behavior is grossly unscientific and unethical. There is a reason why they are hiding away in Cancun, and are not embraced by academic centers.

Rather, Michele Mandel decided to give such clinics free advertising. Her article goes beyond incompetence to reckless indifference to the truth. She is now an accomplice to this exploitation and is responsible for every patient who seeks out such care after reading her article.

Addendum:

More information on this story is available from Orac, who originally pointed me toward the story. Specifically, another article on the story mentioned which Mexican stem cell clinic treated Alda Byers – Stem Cell Therapy International. As Orac points out, this is as bad as you might imagine, with all the red flags for quackery. They make astounding claims to treat a wide variety of ailments and provide no evidence to back up their claims (they basically tell you to look up the subject in PubMed).

We also learn that the Byers spent $150,000 on the treatments – $40,000 to the clinic and the rest on travel and other expenses.

Also, I noted one error in Mandel’s article. She mentions that the clinic is in Cancun, but it appears that it is in Tijuana Mexico. This is not an important detail, but reflects the generally sloppy nature of her reporting.

One of the commenters on Orac’s blog brought up what is an excellent point – by requiring the prescribing of several powerful and risky drugs, which local docs (as in this case) are unlikely to prescribe, the clinic has a ready-made excuse for lack of efficacy of their treatment.

This also raises another ethical issue – beginning a treatment (and charging tens of thousands of dollars) without first establishing appropriate follow up, including prescribing necessary drugs, is malpractice.

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29 responses so far

29 Responses to “Bad Reporting about Stem Cell Treatments for Stroke”

  1. Oracon 06 Apr 2010 at 9:05 am

    You should peruse the website for the stem cell “clinic” that treated Byers. It’s just as bad as you might expect:

    http://scienceblogs.com/insolence/2010/04/stem_cell_therapy_for_locked-in_syndrome.php

  2. daedalus2uon 06 Apr 2010 at 9:05 am

    The prior plausibility issue I have with stem cells for cases where there is actual cell damage is that unless the root cause of the damage is fixed, the new cells will be damaged too.

    In stroke, cells die because there is insufficient blood supply to maintain them in the living state. In the more chronic neurodegenerative disorders (Alzheimer’s for example), there is also insufficient blood supply. Unless you fix the blood supply, won’t the new cells die too?

    I think this is the generic problem with stem cell treatments. Unless you fix the underlying problem that caused the loss of cells, adding more cells won’t fix the problem. I think that if you fix the underlying problem, that you will find that stem cells are not needed. Certainly they won’t be needed if you fix the underlying problem before it causes degeneration.

  3. JurijDon 06 Apr 2010 at 10:02 am

    @daedalus2u

    I don’t entirely agree. While in certain instances you might be right there are a few details that you glossed over in the examples you gave.

    First of all in a stroke the lost blood supply might only be transient and might be restored in a matter of minutes. This time interval when blood flow is depressed can be enough to seriously damage brain tissue. Fixing the damaged brain via some kind of “stem cell transplant” in this instance would be perfectly fine as the root cause is no longer present. (It’s true that one would need to minimize the chances of this happening again in the future but that is a different point to the one you made)

    Secondly even in chronic degenerative neurological conditions if one were to replace some of the lost tissue with new tissue (hypothetically) a patient could perhaps partly regain lost functionality EVEN if the new tissue would later start to degrade as well – and besides one could repeat the procedure again at a later time. And there are some diseases (like say Alzheimers) that seem to result from long-term (decades worth) deposition of certain malfunctioning proteins in the nerves. If you give such a person new brain tissue, one could safely assume it would not be damaged by the diseases primary cause for years or decades to come…

    Thirdly thinking that simply eliminating the root “first” cause of a disease will fix its endpoint is not valid. Think of it this way: a car crashing into a tree is completely wrecked by it…. cutting down the the primary cause of this wreckage – the tree, will not magically fix the car.

    Most diseases produce downstream damage and serious impairment that will not spontaneously heal on its own if you fix the primary cause.

  4. daedalus2uon 06 Apr 2010 at 10:50 am

    The idea that Alzheimer’s is “caused” by deposition of amyloid has not been established. The very small trials in vaccination against amyloid did produce in some individuals a complete clearing of amyloid with no reduction in Alzheimer’s symptoms. This data is incompatible with the “amyloid causes Alzheimer’s” idea.

    My hypothesis is that Alzheimer’s (and other neurodegenerative disorders) is only caused/associated by/with long term reduction in perfusion, and that unless the perfusion is restored the Alzheimer’s cannot be resolved. It is rather complicated physiology that is coupled to many other things that does this, and fixing the perfusion deficit is not easy, it takes increased NO levels. It is better thought of as a NO deficit because it is the NO deficit that causes the perfusion deficit (and other things).

    Tissues are not like cars. Tissues are self-repairing, and are always self-repairing. Mostly those self-repair pathways are not understood, but are the basis for all healing. Good health can be understood as being the result of damage being repaired as fast as it occurs. Degeneration occurs when the damage rate exceeds the repair rate and excess damage accumulates. When you are young and healthy, you can tolerate more damage before things start to fail. When you are older, there is less margin and less redundancy because you have already consumed it.

    If the damage rate exceeds the repair rate, then degeneration is inevitable. Endogenous stem cells are a normal part of the normal healing process. But stem cells, endogenous or exogenous require the proper environment to couple to the normal physiology of the tissue compartment they are placed in. If the environment isn’t right, exogenous stem cells won’t restore proper function.

    If your car crashes into a tree, putting in lots of new spare parts, battery, engine, radiator, radio, won’t make the car drivable if the frame, transmission, and wiring harness are still damaged.

  5. locutusbrgon 06 Apr 2010 at 11:44 am

    Steve
    I agree with your overall point about sloppy reporting, and poor journalism.
    However I think it is a common medical confirmation bias that the lay public in general would not see through this. In the office there are many examples of patients approaching me with new stories similarly written/researched. I am often questioned about news claims with spinal cord injury cases with exaggerated stem cell outcomes. I often do extensive teaching about this especially in young trauma patients. There is not a week that goes by that I do not have to discuss “stem cell” injections and knee OA.
    I find that most lay people understand that if it sounds to good to be true it probably is. Patients/family/friends often approach me for information. I am encouraged by their response to the news stories like this one. Plus the discussion is a great critical thinker primer.
    Let me be clear, I think we should hold a journalists feet to the fire about this type of reporting. Print media is in decline, and the diffuse nature of information dissemination make this kind of inflammatory reporting widespread.
    That said, it is my minority opinion that a majority of people see this for what it is. This type of reporting has too many positive outcomes to be counterbalanced by our negative reactions. Retractions are not headlines.
    The good news is I do not see a mass exodus of my patients to mexico for treatment. Doctors are easy scapegoats for the limitations of current medical treatment. Most people have strong confirmation biases that their own doctor has all the answers so at least they ask the questions.

  6. JurijDon 06 Apr 2010 at 12:20 pm

    @deadalus2u

    —-
    The idea that Alzheimer’s is “caused” by deposition of amyloid has not been established. The very small trials in vaccination against amyloid did produce in some individuals a complete clearing of amyloid with no reduction in Alzheimer’s symptoms. This data is incompatible with the “amyloid causes Alzheimer’s” idea.

    My hypothesis is that Alzheimer’s (and other neurodegenerative disorders) is only caused/associated by/with long term reduction in perfusion, and that unless the perfusion is restored the Alzheimer’s cannot be resolved. It is rather complicated physiology that is coupled to many other things that does this, and fixing the perfusion deficit is not easy, it takes increased NO levels. It is better thought of as a NO deficit because it is the NO deficit that causes the perfusion deficit (and other things).
    —-

    This MIGHT be true but it is irrelevant to the point I was making and also does not rescue your rather dim view of potential stem cell transplants because it is still the case that it takes a long long time for the primary cause of Alzheimers (whatever you believe it may be) to damage neurons. It is reasonable to postulate fresh new neuronal cells via a transplant would also endure for years to come. Your example of neurodegenerative diseases not being helped by such transplants is not valid at all. Sure it might not be a perfect cure, it might need regular re-treatment but to say stem cell treatment is somehow implausible simply because of the this one feature of neurodegenerative diseases/strokes is in my opinion quite fallacious. There are many cases of successful disease treatments that have nothing to do with the underlying cause but improve patient lives incredibly. To deny this potential in stem cell transplants as you did is misguided.

    —-
    Tissues are not like cars. Tissues are self-repairing, and are always self-repairing. Mostly those self-repair pathways are not understood, but are the basis for all healing. Good health can be understood as being the result of damage being repaired as fast as it occurs. Degeneration occurs when the damage rate exceeds the repair rate and excess damage accumulates. When you are young and healthy, you can tolerate more damage before things start to fail. When you are older, there is less margin and less redundancy because you have already consumed it.
    —-

    you are taking my analogy to far and trying to say cars are not like tissues in EVERY way whereas I only said they are in one specific way: the fact that tissues (like cars) can get damaged by a root cause and then cannot always simply repair themselves if the root cause is removed. This is not controversial. You seem to want to imply that tissues can always (or most of the time) repair themselves to a reasonable degree after an insult – this is simply not the case. Irreversible tissue damage is the norm in most diseases even if the root cause is removed.

    Most of what you wrote up there is irrelevant again as it pertains perhaps to a debate about whether it would be appropriate to try and prevent alzheimers before it happens – sure I’m on board with that. This is however was not the point you were making in your first post and not the point I was objecting to. If we go back to that: you were saying that stem cell treatments were inherently implausible because they do not repair the root cause of some diseases. I am saying this might be true but irrelevant because significant gains to patient health can be obtained even if this is the case – and I went further and showed that your 2 examples of strokes and neurodegenerative diseases were not that good of a support for the case you were trying to make as in both examples one can reasonably see stem cell treatments making huge contributions to health.


    If your car crashes into a tree, putting in lots of new spare parts, battery, engine, radiator, radio, won’t make the car drivable if the frame, transmission, and wiring harness are still damaged.

    you did not understand my analogy, apparently. I was saying that fixing the car will not be helped by removing the tree. you are taking this analogy out of context by trying to move it to another point entirely – namely that in your opinion stem cells would only “fix” the brain partly and thus not enough to help – that is a different point and not the one I was objecting to in your first post.

  7. Steven Novellaon 06 Apr 2010 at 12:52 pm

    locutus – you may be right. I don’t know what the percentage is, and I don’t think I made any assumptions about this. But even if a minority of patient give into the false promise of hope, that is still too many. The fact is, these quack clinics thrive on free press through gullible journalism. They get a surge of clients whenever they appear in the media.

  8. daedalus2uon 06 Apr 2010 at 12:52 pm

    JuriJD, let me rephrase things. A healthy human brain has a metabolic demand of 100. The brain of someone with Alzheimer’s has a metabolic capacity of about 75. The metabolic “need” for both brains is not that different. They both need to do the same things, synthesize proteins, neurotransmitters, repair stuff, transport things to where they are needed, maintain cell membrane potentials and such. The Alzheimer’s brain is unable to maintain itself, and so it is in a state of decline.

    When you add stem cells to such a brain, what happens? You immediately increase the metabolic demand by whatever those stem cells consume. A metabolic demand that the Alzheimer’s brain is already unable to keep up with. The stem cells can’t add function until they are incorporated into the already existing structures. How long does that take? It can’t be instantaneously. Axons only grow at a certain rate. New connections can only be made at a certain rate. All of those things take metabolic capacity that the Alzheimer’s brain doesn’t have.

    Back to the car analogy. Suppose your car engine is failing because there isn’t enough oil flow to lubricate everything that needs to be lubricated. Suppose you add additional horsepower (stem cells), but don’t add more oil pumping capacity (blood flow to the brain). You might accelerate the decline of the engine by decreasing oil flow to parts that already don’t have enough by diverting it to the parts you have added before they become functional. If the brain was operating normally and if it had excess blood flow, perhaps stem cells could be added. But we know that the Alzheimer’s brain already has insufficient blood flow. We know it is already in a state of decline. We already know it doesn’t have sufficient resources to maintain itself. Diverting those insufficient resources away from maintenance to support stem cells that are not yet functional may well accelerate the decline.

    I understand this is an analogy, and I also understand that there is insufficient understanding of the root causes, and the paths by which those causes result in Alzheimer’s to dismiss this analogy out of hand.

  9. locutusbrgon 06 Apr 2010 at 1:15 pm

    Steve
    To be clear I don’t advocate surrendering the minority, to the snake oils salemen. I just think that the incentives for this type of reporting are not easy to overcome. I am not certain that a population predisposed to unrealistic thinking will respond well to to the skeptical message. In my opinion there is a resource threshold for addressing poor reporting that is not easily identified. Attack every reporting problem you give quacks legitimacy by arguing and elevating fantasy to the level of evidence. Secondarily we look like contrarians, not true skeptics open to evidence. You and I both know that this is perceptual not factual, but the subtleties are often lost to the public. This can actually be a wedge in the discussion that blurs the facts. Perfect example was the concern about mini black holes and the LHC.
    I am not saying that this example in particular is one that can be left alone. This type of quackery and reporting needs to be addressed.

  10. JurijDon 06 Apr 2010 at 1:50 pm

    @daedalus2u


    JuriJD, let me rephrase things. A healthy human brain has a metabolic demand of 100. The brain of someone with Alzheimer’s has a metabolic capacity of about 75. The metabolic “need” for both brains is not that different. They both need to do the same things, synthesize proteins, neurotransmitters, repair stuff, transport things to where they are needed, maintain cell membrane potentials and such. The Alzheimer’s brain is unable to maintain itself, and so it is in a state of decline.

    When you add stem cells to such a brain, what happens? You immediately increase the metabolic demand by whatever those stem cells consume. A metabolic demand that the Alzheimer’s brain is already unable to keep up with. The stem cells can’t add function until they are incorporated into the already existing structures. How long does that take? It can’t be instantaneously. Axons only grow at a certain rate. New connections can only be made at a certain rate. All of those things take metabolic capacity that the Alzheimer’s brain doesn’t have.

    I’m sorry but this is sheer speculation on your part (the numbers especially are arbitrary to say the least). You are 1.) assuming the root cause of Alzheimers is your pet hypothesis 2.) trying to support your stated position that stem cells apriori have no plausible role to play in treating it based on some highly tentative and elaborate scenario that has currently no support in empirical fact AND is based entirely on assuming you are right in 1.)

    This is the root cause ;) of my objection to your first post. There is absolutely no reason to postulate apriori that stem cells are an implausible hypothetical treatment for such diseases as Alzheimers. Your whole reasoning of this statement is based on assumption upon assumption of what causes such diseases and furthermore that even if you are right in that regard the physiological details will play out in exacly such a way to negate any possible benefit to the patient.

    There is simply not enough empirical data to make such an overreaching statement at this stage of the game – ergo my objection to your first post that stem cells are an implausible treatment simply because they do not deal with some root causes.


    Back to the car analogy. Suppose your car engine is failing because there isn’t enough oil flow to lubricate everything that needs to be lubricated. Suppose you add additional horsepower (stem cells), but don’t add more oil pumping capacity (blood flow to the brain). You might accelerate the decline of the engine by decreasing oil flow to parts that already don’t have enough by diverting it to the parts you have added before they become functional. If the brain was operating normally and if it had excess blood flow, perhaps stem cells could be added. But we know that the Alzheimer’s brain already has insufficient blood flow. We know it is already in a state of decline. We already know it doesn’t have sufficient resources to maintain itself. Diverting those insufficient resources away from maintenance to support stem cells that are not yet functional may well accelerate the decline.

    This was not the point of my analogy. The car analogy pertains only to the fact that some disease-related insults cannot be cured by removing the primary cause – which was clearly stated. You are here trying to take the rough outline of my analogy and make a point of your own by making another, quite different analogy, namely that it MIGHT be that stem cells also have a detrimental effect with some diseases.

    Right you are, this MIGHT be the case, but again your are widely speculating here and again making a different point than the one I objected to: namely that there is some real inherent implausibility to stem cell treatments simply because they do not fix the root cause. This is an absurd statement as much of medicine today cannot cure the root cause but can make a significant improvement to patient health and comfort.


    I understand this is an analogy, and I also understand that there is insufficient understanding of the root causes, and the paths by which those causes result in Alzheimer’s to dismiss this analogy out of hand.

    No, you cannot dismiss this analogy based on our lack of knowledge of Alzheimers as it has nothing to do with that. The analogy was put there to drive home the point that not all diseases can be fixed by curing root causes as you implied and then further emphasized in your second post.

    Lets’ go back to your first post:

    The prior plausibility issue I have with stem cells for cases where there is actual cell damage is that unless the root cause of the damage is fixed, the new cells will be damaged too.

    This is false as it ignores several quite realistic possibilities:

    1. a disease can result in irreversible damage and even if the root cause is removed a patient will not be cured (ie the car has to be taken to a mechanic, cutting down the tree does zipo)

    2. even if some etiologic factor is actively causing harm and we cannot deal with it, a lot of good can be done by dealing with the symptoms

    3. the examples of Alzheimers and stroke that you gave were far from good illustrations of your point because of the reasons I gave and in spite of your objections there are no apriori reasons to assume that
    a) Alzheimers could not be helped by stem cells, there is simply insufficient data to support this contention
    b) you never gave a response to my stroke-objection therefore I suspect you cede that point

  11. JurijDon 06 Apr 2010 at 2:11 pm

    and just to further clarify my position to prevent us from getting swamped in irrelevant details:

    You are basically trying to prove (or at least provide reasonable justification) for a “negative”, namely that stem cell treatment have an inherently low plausibility of working simply because (in your view) they cannot deal with root causes in some instances.

    This statement is wrong on it’s own, as I have shown: it completely ignores the real possibility of helping patients without dealing with root causes which negates much of modern medicine and is just absurd on the face of it.

    Next you gave 2 examples that you think bolster your point by showing 2 diseases that you think could not be helped by stem cells. I took exception to even these two examples you gave and I think I made a pretty strong case for my position that it is much much too premature to state that stem cells could not make a contribution in their management.

    But even if I were to accept these two examples as valid, there a a myriad of other diseases like:
    - heart attacks
    - muscle wasting diseases
    - injuries involving the skin, tendons, muscles
    - aneurysms
    - growing replacement parts like eye lenses, blood vessels
    etc. etc. etc.

    are you really trying to make the case that stem cells are an apriori implausible treatment for all of these? Because you need to do all of this in order to reasonably support the first point you were trying to make in your first post.

  12. jaranathon 06 Apr 2010 at 3:34 pm

    A simple side question: Why could she only blink her eyes? It seems like I hear this often with locked-in cases. Is there a reason voluntary eyelid control is “the last to go?”

  13. daedalus2uon 06 Apr 2010 at 3:58 pm

    We do know that Alzheimer’s isn’t “caused” by a lack of exogenous stem cells. There are adults who do not develop Alzheimer’s and who also never received stem cells. There are stem cells that give rise to neurons in the adult brain. Why aren’t those natural stem cells enough?

    If you look at this paper, table 5, in the frontal cortex they show 83% metabolism (0.80/0.96) vs. 68% metabolism 3 years later (0.67/0.98), in normal controls vs AD patients.

    http://archneur.ama-assn.org/cgi/content/abstract/49/11/1142?ijkey=69089c77d6777ecdf883bcda05674b43bd0ac55b&keytype2=tf_ipsecsha

    There are many other tissue compartments with similar metabolic differences. 75% is not a grossly wrong value, some are higher, some are lower. It does decline over time, and will eventually reach zero (upon death), so at some point it will reach 75%.

    Adding stem cells will increase the metabolic demand without increasing the metabolic capacity.

    The “best” time to treat Alzheimer’s is before there is lots of damage, the sooner the better. A treatment that is initiated before there is much damage doesn’t need to repair damage, all it needs to do it prevent damage in the first place.

    There is no reason to suppose that if fully functioning normal cells were somehow beamed into the brain of an Alzheimer’s disease patient and connected (via Scotty’s transporter), that they would somehow function normally at only 75% power. They would very likely fail too. Since it is not known how to restore normal metabolism to the brain, there is no reason to suppose that a few stem cells would restore normal function. They might fail slower, or they might fail faster. I see no reasons to suppose that failure would be delayed long term. I would expect it to proceed at the same rate as the rest of the neurons or maybe faster because the stem cells need to grow to do anything and so they need a higher metabolic rate than the already existing neurons which are dying.

    In most cases, when cells in the brain die, they do so via excitotoxicity, by being stimulated until their metabolic capacity is exceeded. Using this method allows the brain to “prune” the “weakest links”, prune those cells that have impaired mitochondria biogenesis capacity. Once the bad cells are pruned, remaining cells can be recruited to take over what ever those cells were doing. At least until there are no more extra cells left.

    I haven’t commented about stroke because I don’t know as much about it. I know a lot more about Alzheimer’s and the other chronic neurodegenerative diseases.

    In any case, injecting stem cells is not “fixing the damage”. It is injecting stem cells. Will those stem cells divide and differentiate and integrate themselves into the already existing neuronal network in ways that provide function? That is a good question, and no one knows the answer. They probably can, endogenous stem cells do, so exogenous stem cells can probably be induced to do so also. But in the case of the degenerative diseases, the endogenous stem cell recruitment has failed. Does that mean that exogenous stem cell recruitment will fail also? I think it does, but that remains to be seen. Until the reason(s) for endogenous stem cell recruitment failure are known and corrected, I think it is a reasonable default position. To me, that does not mean stem cell research should be stopped, but rather that the causes of endogenous stem cell recruitment failure should be investigated too.

    I didn’t mean to imply that I saw no role for stem cells, but in the case of degenerative disorders, unless the cause of the degeneration is found (and fixed), the new cells are going to degenerate too. Preventing existing tissues from degenerating is going to be a better approach than letting tissues degenerate and then replacing things that have degenerated (at least for the foreseeable future).

    I think for all of the diseases you mention, prevention would be better than cure via stem cells. Many of those tissue compartments all ready use stem cells to maintain themselves. When those tissues fail, there is something that has gone wrong with the normal stem cell recruitment, proliferation, differentiation and incorporation into the working tissue. Without understanding what has gone wrong in the degenerating tissue, I don’t think there is a reasonable expectation that stem cells will be a panacea. Maybe they will be for something, but until that happens I am not going to hold my breath.

    In the case of organ transplants, in many cases the new organ fails much more rapidly than it would have failed in the body of the donor, and not because of rejection. A stem cell derived organ would be expected to fail more rapidly too.

  14. stompsfrogson 06 Apr 2010 at 5:42 pm

    d2u needs his own blog. he could call it “I have a woody for NO.”

    Back to the Mexican stem cells… I hope Michele Mandel sees your blog, Steve. And feels bad. She’s definitely destined for a career in local news. (That was an insult – I hate local news. )

    I hope they can fix brain damage from strokes with stem cells soon. My great grandma just had a few :( She can’t remember me, but at least she knows better than to go to Mexico.

  15. daedalus2uon 06 Apr 2010 at 6:44 pm

    Stumpsfrogs, I do have my own blog.

    http://daedalus2u.blogspot.com/

    In case you didn’t know, “woodies” are caused by NO, so everyone has a woody for NO. ;)

  16. CivilUnreston 06 Apr 2010 at 6:56 pm

    d2u, I think you’re missing JurijD’s point:

    The problem is that you are making assumptions about treatment outcomes based on an unproven hypothesis about the “root” cause of Alzheimer’s.

    IF the hypothesis that you favor turns out to be correct, you may very well be right. There are many people researching this disease, however, and I think you’d be hard-pressed to get a consensus on what the underlying cause is (if there even is a single cause!).

    Also, I’m sure anyone will agree with you that preventing a serious disease and avoiding major tissue damage in the first place is always the best option. The problem is that it isn’t always an option. Many people, with and without preventative interventions, experience debilitating injuries that won’t heal fully on their own.

    Stem cell research is a promising field for those people. I have no idea if giving someone stem cells will turn out to be the best treatment (personally, I would bet that the best treatment is figuring out how to activate endogenous stem cells), but I agree entirely with JurijD in that there is absolutely no reason to count stem-cells out as a valid form of repairative (is that a word?) treatment.

  17. daedalus2uon 06 Apr 2010 at 8:22 pm

    CivilUnrest, you and JuriDG are assuming I don’t know what I am talking about without knowing what I know. I know the Alzheimer’s literature very well, and the “amyloid hypothesis” isn’t proven either. I think it has been disproven by the amyloid vaccination studies. The “amyloid hypothesis can’t explain why when amyloid is removed there is no improvement. To me, that calls into question the fundamental premise. The “amyloid hypothesis” also doesn’t explain the prompt improvement when Etanercept is injected into the CSF. You have to look at the whole literature. When you do that, there are credible alternatives to the amyloid hypothesis, alternatives which I think are more plausible because they are compatible with more of the literature than the amyloid hypothesis is.

    Accumulation of amyloid is not confined to Alzheimer’s, and is not confined to the brain. The actual function of the amyloid protein that accumulates in Alzheimer’s is unknown. There is some recent work that it is an excellent antibacterial agent, as good as any other antibacterial protein. It turns out that Tau is elevated in neurosyphilis. Is that a “feature”? Could be. Some of the symptoms of neurosyphilis are similar to some of the neurodegenerative diseases and in neurosyphilis they resolve if treatment occurs early enough. Neurosyphilis causes Alzheimer’s-like symptoms that can be reversed. Can the neurosyphilis-like symptoms of Alzheimer’s be reversed? Etanercept in the CSF does that, I think via a NO mechanism.

    The stem cell advocates are making the same assumptions you are faulting me for; assuming that stem cells will work without understanding the fundamental causes of the disorders. I am not saying they won’t work, just that I consider them implausible because of my own understanding of the disorders. You can’t just add cells and assume they will integrate and work properly. The stem cell advocates don’t know how to control the proliferation, differentiation and integration of cells into complex neurological structures. All they can do is add the stem cells and then hope they connect correctly. Maybe they will, but there are vastly more incorrect ways they can connect that correct ways, and there is already substantial derangement of many pathways in the brain of an Alzheimer’s patient.

    So far there haven’t been any successful stem cell treatments (that I am aware of other than bone marrow transplant which I think is a special case). There have been some experiments that caused tumors. There are lots of quacks that inject people with what they say are stem cells. Probably they are not stem cells, or they would be causing a lot more tumors than have been reported. Probably they are just injecting cells that get killed and cleared by the immune system. In one of the Chinese clinics they report the “reaction” indicating the stem cells are working as flu-like symptoms. The classic signs of immune system activation. Causing more inflammation in the brain would very likely worsen Alzheimer’s (that was the reason the amyloid vaccination trial was halted).

    I am not saying there should be no research on such things, just that the research should not be hyped beyond reasonable extrapolation. Too much hype is a major problem in science publication these days. Tiny insignificant advances get pimped and hyped beyond all reason, and “real” advances languish (and can’t get funded) because no one understands them except the few experts working on them.

    I happen to agree with you that the “best” treatment will turn out to be activating endogenous stem cells. One of the factors that regulates stem cells is NO through the NO/sGC/cGMP/PKG pathway. There is also NO via NFkB, VEGF, HIF, and not a few others. A lot of the migration of cells is regulated by NO, and most stem cells have to migrate to get to where they are needed. I think that more NO will help. Can I prove it? Not yet.

  18. Steven Novellaon 07 Apr 2010 at 12:13 am

    Locked in syndrome can be caused by a brainstem stroke – in a particular part of the brainstem that allows a patient to be conscious and is also below the point of the pathway for voluntary control of the eyes. So it’s just about the pathways in the brainstem.

  19. ccbowerson 07 Apr 2010 at 1:23 am

    # daedalus2u

    “My hypothesis is that Alzheimer’s (and other neurodegenerative disorders) is only caused/associated by/with long term reduction in perfusion”

    This describes vascular dementia. Are they one and the same in your mind?… because not all people with dementia have amlyoid deposits like this as you know, which I believe is why there is a distinction. I agree that the evidence does not suggest a simple amyloid cause for dementia.

    I gather that your position is a reaction to stem cell advocates, but I agree in principle with JurijD’s criticisms. You seem to be ‘strawmanning’ stem cells by criticizing the extremist view. Of course just injecting stem cells by themselves where you want stuff to grow is not going to be the answer.

    The ‘not addressing the root cause’ argument is a bogus one. Most treatments are not cures and do not address root causes, but may have great (or small or moderate) utility. For example, no one argues that treating hypertension addresses root causes, but it prevents strokes, CHF, MIs, etc. If stem cells could prevent disease progression for 10 years (not that I’m saying they will), that may not get at a root cause, but would effectively be a cure for many people (for those who would die by then). Even a few years is alot in alzheimer’s where people often don’t live long after diagnosis.

    “I think for all of the diseases you mention, prevention would be better than cure via stem cells.”
    – So what, that is always the case. That applies to all acquired diseases, but is irrelevant. We have to have a multipronged approach to attacking diseases, and if we can treat after the fact, then great. It does no good to someone with a disease to say “we only know how to prevent this disease, not treat it.” We have to be able to do both.

    You are correct in that stem cells have been overly hyped, and this may backfire in the public’s view years down the road (like the war on cancer), but let’s counter hype with a balanced view not antihype.

  20. BillyJoe7on 07 Apr 2010 at 8:28 am

    Here’s an example of responsbile reporting:

    The ABC’s “Foreign Correspondent” recently did a sceptical piece on stem cell treatment available in places like Russia, Tijuana, and the Dominican Republic. They followed a family with a child with a rare disorder causing blindness. Their community raised the $20,000 to take her over to the last mentioned destination. On their return the parents were convinced their daughter could now see and the media proclaimed a miracle had occurred. The scientists tested her and found no difference in her vision. The parents remain convinced she can see.

    http://www.abc.net.au/foreign/

  21. jaranathon 07 Apr 2010 at 10:07 am

    Thanks, Steve. Remind me to never have a brainstem stroke…

  22. lordrunningclamon 07 Apr 2010 at 12:52 pm

    Stupid question here: If they can afford $150,000 to travel back and forth to Mexico for treatment, why can’t they afford, say, $1,000 (at most) to have one of them fly to Mexico, pick up the prescription at the clinic, fill it in Mexico and fly back?

    Is it because the “doctors” a the clinic aren’t real doctors and can’t actually write a prescription? The fact that a Mexican doctor told them to get a Canadian doctor to write a prescription for them sounds fishy to me. Why didn’t the Mexican doctor just write the prescription and phone it in or mail it? Are prescriptions invalidated as they cross international borders? (Seriously, I have no idea about that last point.)

    I think the real subtext of this article is the family and the reporter bitching because the Canadian health system won’t pay for their phony-baloney treatments.

  23. daedalus2uon 07 Apr 2010 at 4:05 pm

    Ccbowers, I was not talking of comparing stem cells to “most treatments”, I was talking about using stem cells to treat degenerative diseases. I completely agree with you that the answer to hype is not anti-hype, but rather a balanced view. I think that is what I have.

    It is difficult to present ideas with great promise without them sounding like they are being hyped. This is a problem I have with my nitric oxide research. It is difficult to portray it without it sounding “too good to be true”. When Michael Faraday was asked (in 1850) by William Gladstone, then British Chancellor of the Exchequer, “what was electricity good for?” He said “one day you will tax it”. I don’t think that Faraday would be surprised by anything that electricity is being used for today. I think there were only a handful of people at the time who could appreciate what electricity could do while realizing it was not hype.

    There was a recent news article about using fat-derived stem cells to make scaffolds of bone-like material that could be grown in vitro and then implanted. I think that is a fine use of stem cells, one that will very likely be technically successful. Using stem cells to generate material for cosmetic and functional repair of tissues injured in accidents is likely to be useful medically. Whether it will be commercially successful is another story. It will likely only be useful in a limited number of disorders, where new structural materials are needed.

    I think the higher metabolic load organs, liver, heart, kidney and brain will be much more difficult because they usually degenerate from the “inside”, that is they are not injured through trauma (except xenobiotic liver or kidney failure, but then it would take too long to grow whole organs from stem cells) but rather degenerate through “natural” and as yet poorly understood mechanisms.

    Virtually all existing treatments don’t actually “repair” any damage. They set up conditions so the body can repair the damage by healing. In individuals who have degenerative diseases, the healing rate has slowed way down. Healing is a complex process. It requires a complex control system. When healing is slowed, healing still occurs, the “process” still proceeds, just at a slower rate. To me, this suggests that the slow-down of healing is still under physiologic control. I think that slow down in healing is an outcome of the normal regulation of the allocation of resources. If there isn’t enough ATP, the body doesn’t want to “waste” it on something it doesn’t need. Rapid healing is a “luxury” for organisms that are in good health. If you are in bad health, you can’t “afford” to heal rapidly. The understanding that fundamental aspects of physiology such as healing rate are regulated and controlled by physiology is not well appreciated. I think if it were, then the role of stem cells as potentially one step in a complex chain of processes leading to restoring function would be better appreciated.

    All of the neurodegenerative diseases are characterized by reduced brain metabolism. I happen to think that is a much more important symptom than the accumulation of amyloid, or Tau, or Lewy bodies, or lipofuscin. There are only two pathways by which damaged proteins are recycled and cleared inside of cells, the proteasome which clears damaged proteins one molecule at a time, and autophagy which clears volumes of cytoplasm and so can handle large aggregates of damaged proteins. Both of those protein recycling pathways require ATP. When they are inhibited artificially, deposits of “gunk” accumulate. When you reduce ATP levels “gunk” accumulates.

    Degenerative diseases are all characterized by reduced ATP levels. I think that restoring ATP levels will greatly improve the course of degenerative diseases. People are not used to thinking about ATP as something that is regulated and which can be changed. Getting people able to think about such things is important before they will be able to consider treatments based on improving ATP regulation.

  24. daedalus2uon 07 Apr 2010 at 10:58 pm

    I came across an excellent use of stem cells today, but it was for research, not for treatment. The researcher took cells from the skin of someone with a genetic abnormality, turned them into stem cells, then differentiated them into nerve cells to do research on human nerve cells growing in culture with the actual genetic abnormality without taking a biopsy of human nerve cells.

  25. borealyson 10 Apr 2010 at 11:38 am

    Why didn’t the Mexican doctor just write the prescription and phone it in or mail it? Are prescriptions invalidated as they cross international borders? (Seriously, I have no idea about that last point.)

    They are.

    I can’t even pick up a prescription in the province of Ontario that was written by a doctor in the province of Quebec, never mind one written outside the country.

    The reason is pretty simple — doctors and pharmacists in any given jurisdiction have no control whatsoever over professional regulation in other jurisdictions. If a doc from a poorly-regulated region (say, I dunno, somewhere in Mexico) writes a prescription, a pharmacist in Toronto has no guarantee that the prescription meets the accepted standard of care in Ontario. Providing the medication under those circumstances would be unethical.

    For the record, having lived in the Toronto area, I should point out that the Toronto Sun (where this story appears to come from) is a notoriously bad rag of a newspaper, with credibility just a smidge above a supermarket tabloid.

  26. Plittleon 11 Apr 2010 at 9:25 pm

    Michelle Mandel’s at it again, is she? I complained about her reportage on Jenny McCarthy a couple of years ago: http://aurorawalkingvacation.blogspot.com/2009/04/jenny-mccarthy-body-count.html
    At that time I characterized Mandel as attempting to write a skeptical article, but losing her way as she went. Having read this article, however, I am now not so sure. She may have just been pretending to a skeptical position in order to make her “conclusion” seem more rational.

  27. [...] stem cell transplants for a long list of fatal or incurable diseases, like ALS, spinal cord injury, or stroke. They seem to be deliberately targeting affluent Westerners – although many of their victims [...]

  28. mcwhippeton 27 Jun 2012 at 11:18 pm

    If all of you likely didn’t have the drug companies in your back pocket, and actually stopped postulating and posturing, you would likely see there is a whole world out there where cures and medical breakthroughs do happen. Canada is the sore on the backside in the fight to win medical wars. We are so backware and incestuous with drug company paid off people, it’s sickening. Why don’t you, in all your infinite wisdom, open your eyes – better yet – why don’t you go visit Alda Byers. Get your heads out of your educated asses and understand that medicine and treatment takes on many forms and if we can find help elsewhere, we should grab on to it and embrace it!

  29. ChrisHon 28 Jun 2012 at 4:08 pm

    mcwhippet:

    If all of you likely didn’t have the drug companies in your back pocket, and actually stopped postulating and posturing, you would likely see there is a whole world out there where cures and medical breakthroughs do happen.

    Oh, how droll, it the the old tired and boring Pharma Shill Gambit. Perhaps next time instead of using insults you might try posting some actual verifiable evidence. Because, insults are also boring, and using them as a form of debate is more a reflection on the quality of your statements (none).

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