Today’s post is my no-B.S. guide to the possibility of stem cells for Multiple Sclerosis (MS).
There is a great deal of buzz about using stem cells to treat or even cure multiple sclerosis.
How much of this stem cell buzz is real hope and how much is hype?
Symptoms and standard MS care
MS has a host of symptoms.
For many patients, conventional chemical medicines do a reasonable job managing the disease. However, for others the disease relapses, is unacceptably resistant to treatment, or the medicines have severe side effects.
New, safer and more effective therapies are desperately needed for multiple sclerosis.
The specific potential of stem cells for treating patients with MS is exciting and gives hope, but realistically there is tons of hype.
I know a lot of people with MS and many more contact me with generally the same question: can stem cells treat or cure MS today?
My best answer is “Maybe someday that will happen and I am hopeful, but that day is not today and it won’t even be this year or next.”
The most commonly sold stem cell intervention for MS at present involves IV injection of mesenchymal stem cells (MSCs) from either fat or marrow. Many times the MSCs are propagated in a lab prior to the transplant.
Challenges of using stem cells for multiple sclerosis
Below I outline the key issues and challenges with using stem cells today to treat multiple sclerosis.
To grow or not to grow? One of the most important issues in the arena of using stem cells to treat MS is whether (A) to use straight, non-manipulated stem cells that are freshly harvested or (B) to grow the cells in culture first to greatly increase their numbers. The advantage of (A) is that the less manipulation there is the fewer regulatory hurdles one is likely to face, although non-homologous use plays in here even if the cells are not grown. The disadvantage of (A) is that you may have only a few million true stem cells in the mix and that is thought, even by most experts in the for-profit clinic field that I have talked with, to simply be not enough to make any meaningful difference. Think drop in the bucket, or perhaps more like a drop in an ocean of the human body. The advantage of (B) addresses this issue. If via growth you can give a patient a billion rather than a million stem cells, you might have a profoundly more powerful therapy. However, the big problem for clinics is that growth in culture makes stem cells a drug subject to more practically challenging and expensive FDA regulatory oversight due to safety concerns.
Getting stem cells into the CNS. One of the challenges of treating MS with stem cells is that it is a disease of the central nervous system (CNS) meaning the brain and spinal cord. As it turns out the brain and spinal cord are protected from the rest of the body by the blood-brain barrier and cerebrospinal fluid blood barrier (let’s call them collectively the “BBB”). The BBB is vitally important because our bodies need to keep many things out of the brain and spine so that we can remain healthy. This potentially neurotoxic “stuff” that is excluded from the CNS can include outright toxins, chemicals that might change brain function, and pathogens like viruses and bacteria.
Without the BBB we all die.
However, the BBB makes it therapeutically challenging if not impossible to treat neurological disorders such as multiple sclerosis, autism, Parkinson’s, Huntington’s, and others with cellular therapies administered by IV injection. Cells are huge compared to many of the small molecules that the BBB filters out.
How exactly do you get cellular medicines into the CNS to treat such diseases if the BBB is in the way?
The answer is that you don’t get stem cells into the CNS via IV injection. (Update: it should be noted that in some disease states the BBB is somewhat compromised and some cells may more readily enter the CNS than usual. Also, although the evidence that MSCs can cross the BBB is very limited, other types of cells such as human cord blood cells may have higher intrinsic potential to enter the human CNS from the bloodstream. However, even in this case, the published evidence is very limited at this time.)
Often IV injection of even traditional chemical “pill” medicines into the bloodstream or ingestion of such medicines won’t work for CNS disorders because the BBB keeps them out, sometimes even super tiny molecules.
Therefore, you can imagine relatively huge things such as stem cells just do not make it across the BBB. That is literally like trying to push an elephant through the tiny holes in your colander. Maybe sometimes one strand of spaghetti will hang out part way through a hole in a colander after being drained, but not even the tip of an elephant’s trunk can fit, let alone the whole animal.
So what can be done to get stem cells into the CNS?
Some legit proposed stem cell therapies for CNS disorders interestingly invoke direct injection of the cells into the brain itself. I just saw a talk on this recently and it works to get cells into the CNS. A small hole is bored in the skull and a very fine needle is inserted via a device that can pinpoint the location of the injection of the cells. Fortunately, you usually don’t see for-profit clinics offering to inject stem cells into people’s brains. They go the IV approach instead almost 100% of the time, although some do sell high risk intra-thecal (spinal) injections of stem cells.
What this all means is that the clinics selling IV stem cell transplants for treatments of MS are either (A) selling a load of BS that the stem cells can get into the brain from the blood and do good stuff or (B) have to invoke a different theory that IV injections of stem cells do good things to the CNS indirectly.
Let’s talk more about the latter (B) option.
Helping Multiple Sclerosis indirectly via immunomodulation?
What good things could stem cells do for MS indirectly via that (B) option above and how would that work?
The idea is generally based on the fact that MS is an immunological disorder. The body attacks its own nerves in the CNS, damaging or destroying them. Stem cell clinics pitch the idea that injecting say a billion stem cells into the blood stream via a vein could help MS indirectly through immunomodulation, meaning calming down the immune system in general. In other words, they claim that by flooding a bunch of stem cells into the blood stream the patient’s general immune system activity will be lowered and that in turn will help MS by lessening autoimmune attacks on the nerves even if not a single cell makes its way into the CNS. It’s a good idea in theory, but in practice I’m not convinced that there is much evidence to support it actually working as an MS treatment today.
What are the issues with this potential approach?
A hit-and-run medicinal effect for the diseased CNS of MS? Unfortunately, in fact, there are some big problems with this indirect idea. First, stem cells from fat or bone marrow are not supposed to be floating around willy-nilly in the blood stream and your body knows this. As a result, your body filters all these stem cells out, mostly in the lungs (where potentially life threatening pulmonary emboli can form), and kills nearly all of them within hours. Autopsy studies of patients who received stem cell transplants of this kind show that essentially zero stem cells “engraft” (meaning stably find a home and survive) within the human body for years. Katarina LeBlanc’s lab published an incredibly important paper on this that you can find here. I highly recommend reading it.
What this means is that for IV administered stem cell transplants to help MS patients, they must within a period of hours (or at most a few days) have a powerful, helpful, and lasting effect on your body’s immune system. In science this is called a “hit-and-run” mechanism.
Even if we assume for the moment that the transplanted stem cells do indeed have a clinically meaningful calming effect on the immune system in MS patients that still is not enough by itself. This effect must last for years to help MS patients, who cannot get stem cell injections running $10K-$20K a pop every few weeks, right? That is impractical and would greatly increase the risks of side effects to patients.
The bottom line is that today there is no compelling scientific or medical evidence that IV stem cell transplants of this kind can help MS patients.
If providers here in the US or those in foreign clinics such as in Panama or elsewhere selling this kind of therapy truly believe that these therapies work, they owe it to patients and to the stem cell community to collect data and publish it in journals or an online database.
Anecdotal evidence or testimonials won’t cut it. Show us all in the stem cell community real data.
Designer stem cells. One area that has promise, but will take as much as a decade or more to realize, is the production and use of designer stem cells that might treat MS. What do I mean by “designer stem cells”? These laboratory-produced stem cells would be made to secrete either the same stuff that stem cells naturally make but to a greatly increased extent (think 100,000 fold higher) or to secrete man-made medicines that are helpful for MS. Another idea is to make stem cells that are sneaky and somehow do not get eliminated by the body so they can hang around and do good stuff long term or sneak past the BBB.
In these kinds of ways, designer stem cells injected IV or directly into the brain might effectively help MS. It’s almost like a doctor being able to go inside your body and your CNS in this case and treat it from the inside out. However, this comes with associated elevated risks. Designer stem cells would almost certainly have a much higher risk of causing side effects such as cancer.
Take home and looking ahead
Stem cells have very important, real promise for Multiple Sclerosis in the long run as in the coming decades, but the science today does not support their use now in the ways that non-compliant or foreign stem cell clinics are selling them.
The risks from stem cell interventions for MS today such as infection, cancer, pulmonary embolism, and worsening of immune symptoms just to name a few are simply too high to justify the clinics selling a therapy that has no proven benefit.
I realize there are many people with multiple sclerosis who are suffering and for whom today’s conventional medicine has too little to offer, but at least for now I believe that stem cells are not the answer. To be clear, I do not judge patients who get such treatments. Rather, I worry about them in terms of their safety and their being exploited by people who in most cases are just after their money.
I’m critical of the not-read-for-prime time technology and the people selling it today, not the patients who are their targets.
Note: This post is not medical advice. I am not a medical doctor and all medical decisions should be made with your own physicians. This post is for general educational purposes on multiple sclerosis only.
http://www.news-medical.net/news/20120927/Adult-stem-cells-can-prevent-Alzheimers-disease.aspx
http://www.stepahead.org.au/media/pdfs/Adultstemcellsandspinalcordinjurytreatment.pdf
The cells migrated through the blood brain barrier, thought by many to be impossible for adult stem cells to cross, and went into the brain
Dear Paul,
I GREATLY appreciate all the information you have shared about stem cell treatment and MS. I just found out (August 18, 2013) about adipose-tissue stem cell treatment for MS patients.
At first, I thought, “How does that work?” How is is administered? How long between harvesting the stem cells and administration of said cells (do they have to be cultured/grown)? What about the BBB???
My concerns were for a lady who apparently is in the Bahamas for a two-week stem-cell therapy to “cure” her MS.
You answered ALL the questions I had regarding the process.
As you mention for your self, my concern is also for the lady’s safety.
I myself have Secondary Progressive MS (I initially had Relapsing-Remitting for the first 15 years, then it got “promoted”) 🙂 My interest was piqued when I found out about this latest treatment, but I had my questions and my doubts.
You successfully answered all of them. 🙂
Thank you.
Sincerely,
Hélène Marcotte
Dear Helen,
If I may suggest, before considering any treatment do your own due diligence and talk to specialists in the field instead of basing your decision on blogs and forums. Some of the anwsers you might get here or in other blogs are clearly flawed.
There are currently several clinical trials for MS at ruputable hospitals (not in Panama!!!) that might be worth a try. Currently, none of these treatments promise cure, but might be able to do some benefits. Their aim seems realistic.
As far as I know even halting progression for a few years might be a great thing that only patients can appreciate. I really hope that some of the clinical trials for your disease and for others will prove some benefits in the near future.
Dear BePrecise,
Thank you for your considerate and kind comment 🙂
I have no intention, presently, to get any invasive treatment done for my MS….. I am too much of a scaredy-cat 🙂
I appreciate your cautioning of doing my own due diligence. That is the reason I looked into the stem-cell claims.
Have an excellent day! 🙂
Sincerely,
Hélène Marcotte
Dear Helen,
no offence to anyone, I just wanted to say that the best way if someone is reading official papers from clinical trials and other official sources and talks to well-respected experts rather than relying on second hand opinions.
Unfortunately, today, there is no distinction made between scientifically well based methods and bogus, scam treatments.
I really wish you a good health.
BP
Dear Beprecise,
I’m a bit confused by:
“You also just touch an important delivery method that is lumbar injection. This way you get the cells into CNS.”
Are you saying that an epidural injection to the lumbar region will efficiently get MSC to the brain?
Hi Brian,
“Are you saying that an epidural injection to the lumbar region will efficiently get MSC to the brain?”
Yes, in clinical trials, MRI shows that the labeled cells migrated into the brain. During the clinical trials they used both intravenous and inthratecal injections.
I really value the caution of the author of this article, but the use of MSCs are pretty safe. More caution should be devoted to the place where someone gets the treatment. Would you get a heart surgery in a shady clinic in a country which has lax regulations?
Dear Paul,
Last time, you made quite a few mistakes with regard to quoting from the Lanza presentation on hESC applied in the animal model of MS and this time with regard to potential MSC treatments in MS.
You are mixing clinics in Panama and in other third world countries that offer not more than snake oils for money with the use of straight, non-manipulated stem cells that are freshly harvested with those that do culture expansion. This latter approach is already in clinical trials in the UK and the US at reputable clinics. Previous clinical trials with culture expanded MSCs demostrated efficay in Phase 1/2. This method is laborous as it requires circa 3 months of culture expansion.
You also just touch an important delivery method that is lumbar injection. This way you get the cells into CNS. The mesenchymal cells were marked in clinical trials so that the scientists could track them and verify that they reach the intended destination in the patient’s body. So, your argument that MSCs can not enter the CNS with current delivery methods is just not true.
Phase 1/2 clinical trials just involve circa a dozen patients so far reaching conclusions can not be drawn from them, but we have to see that already several Phase 1/2 clinical trials have come to the same conclusion that circa 70% of the patients benefited from culture expanded MSCs infused at least partially by lumbur puncture. And no serious side effects.
You got it right, however, that adult MSCs do not have a long lasting effect. According to the current information from clinical trials their effect lasts for only circa 6-12 months. Also, if you consider that the median improvement achieved by this method is circa 0.5-1.0 in EDSS, then you should realize that patients can gain a year or two by turning the clock back this way. That is something that no drugs can emulate today.
You should also know that Lanza is working on hESC derived MSCs and according to his public speeches this method has a long lasting effect in mice MS as compared to the short lved effect of adult MSCs.
Also, you did not mention the differentiated MSCs that will be soon in clinical trials and nothing was said about HSCT either.
So, I think you painted an unnecessarily pessimistic picture for the prospects of stem cells in the treatment of MS, even though, we all know that currently MS can not be cured.
Has anyone heard Robert Lanza of ACTC discuss his experience with Embryonic MSC’s and M.S..in mice.According to his experience he has seen paralysed mice get up and run after treatment with his HEMSC.Like most embryonic cells,they just seem to work much better than adult MSC’s.His imput on this subject might be interesting.
Interesting and makes a lot of sense. However, from a non medical person like myself, this explanation of the BBB does not make sense, because I am thinking how we are told to eat foods that are good for the brain (eg. Omega 3s, etc). These foods are not injected directly into the brain but I presume they go through the immune system or blood system or the like? Am I correct?
Paul, I think you are also know of many MS patients who have had quality of life improvements after stem cell therapy. Why no mention of them? Of course, everyone wants a cure to all that ails mankind, but quality of life improvements, no matter how insignificant they might seem to someone who is healthy, are very important to patients. I know of very few clinics that claim they can cure patients. If you have the names of any, I will be glad to red flag them on my site.
Patients have their own grapevine and no matter how much blogging you do on the subject, it isn’t going to deter seriously ill patients who talk to other patients who are seeing improvement. If you have a some other alternative suggestions for no option patients, I know we would all be glad to hear it.
You make some good points, Barbara.
I want the lives of patients to be improved including quality of life aspects for sure.
In the end my bias as a scientist is to see data.
In fact clinics could be collecting data on quality of life and publishing it either in journals or in online databases. I’m all for that.
If this stuff really works & is safe, why not let the world know about it via the most universal of languages: data.
It’s really a shame that almost none of the clinics will collect or publish data. I think that’s disrespectful to the patients who have put their faith in the clinics. So as I’ve said before, let’s pressure the clinics to collect and publish data.
If no option patients make the decision to get a stem cell intervention it’s not my place to judge them. I wish them the best and won’t criticize them. I never have.
Instead, I judge only the clinics & those docs for the many reasons I’ve mentioned before, mostly having to do with them not taking proper care of the patients and taking advantage of patients.
Here’s a xeno study with specifics on what the cells did after passing BBB “Human adipose tissue-derived mesenchymal stem cells improve cognitive function and physical activity in ageing mice.”
http://www.ncbi.nlm.nih.gov/m/pubmed/23404260/
And another discussion debating the ability of SC to reach the brain
http://www.regenexx.com/injecting-stem-cells-iv-means-only-00005-reach-their-target-in-the-brain/
Paul, I’ve never met a patient who got a whole drilled in their head to receive stem cells. Intrathecal spinal injection is what is used to reach the brain.
Thanks, SammyJo. The direct brain injection route is likely to become far more common in the next 5 years I would predict based on talks I’ve seen and seems promising as a delivery method as much as it is a tad creepy to think of a hole in the head and cells being put right in there. Isn’t intrathecal very inefficient for getting cells into the brain?
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“Evidence for crossing the blood barrier of adult rat brain by human adipose-derived mesenchymal stromal cells during a 6-month period of post-transplantation”
http://www.sciencedirect.com/science/article/pii/S1465324913004519
Thanks for the link. This paper is a xeno study reporting some cells put into the rodent brain end up in the spleen–that could be due to damaged blood vessels from the brain injection. Clinicians are hoping to go the other direction from the blood to the brain.
I agree that BBB could be much more complicated and trickier in terms of cell permeability than we think. There are some experimental studies (can’t get a link right now), which demonstrate that human cord blood cells migrate into the brain tissue of rodents in stroke models. More of that, there is a clinical case, reported by Evan Snyder /Joanne Kurtzberg, which showed cord blood cells into the brain tissue of patient with Krabbe disease. It was done on postmortem autopsy material.
So, human mononuclear cells migrate into the brain if infused iv. But the most important questions:
(1) do we want (need) them to migrate and stay there?
(2) if they migrate what do they do there and what their long-term fate?
(3) how many cells should engraft and persist in the brain for therapeutic effect?
We don’t have answer to all these questions as for now.
Thanks, Alexey, for the comment.
The folks I’ve talked to who know more about the BBB than I and are experts on stem cell transplantation were very skeptical about this concept. They don’t believe that anyone has really gotten clinically meaningful levels of useful cells from the blood into the CNS of human patients on a consistent basis.
Certainly in some disease states the BBB is compromised– that should have been mentioned in my blog post.
If one assumes that some IV administered cells do get into the CNS, I think your questions are excellent. I agree we don’t have answers. I wish there were more published studies on this area. If anyone has links to more relevant papers please post!
Here’s a UCB clinical trial ongoing for CP: http://clinicaltrials.gov/ct2/show/NCT01147653?term=NCT01147653&rank=1. They assert in the details:
“CB also engrafts and differentiates in brain, facilitating neural cell repair, in animal models and human patients with inborn errors of metabolism undergoing allogeneic, unrelated donor UCB transplantation.”
What are the papers supporting these statements?
Hi Paul,
I know the subject is MSC’s and I agree with you on the IV and BBB in that. But shifting gears a bit in regards to the BBB, I’d like to point out that CD+34 cord blood cells have been proven to transcend the BBB.
http://www.dukehealth.org/health_library/news/7582
Granted this articles focus is on donor units with immuno-suppression, however, there are on going autologus / non suppression Neuro regenerative studies at Duke (CP/TBI/near-drowning ect.) that are showing incredible promise. Paper is due out in 2016.
Thanks for the link, Super. Is there a link to the actual paper on this?
Hi Paul,
Re your question, see references 22-25 in:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3682484/pdf/nihms-94583.pdf
Thanks. This is super helpful reading material I have to dig into.
The following publication raises the possibility that the blood-brain barrier might be a little more nuanced than you seem to suggest.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3586765/
My reading is that our MSC are probably doing good things for our bodies. Until some clever people find good ways to artificially utilize MSC, maybe it would be good to know what we can do to keep our own, natural MSC in tip-top shape?
Brian, you make some good points. I have added an update to the article to include a few caveats.
In terms of what we can do to take care of our own MSCs, that’s a fantastic question. I don’t have all the answers, but in my upcoming book, Stem Cells: An Insider’s Guide, I propose some ideas on this. There are all pretty much common sense things like diet, exercise, etc., but linked to stem cells.
Paul,
Very well said. I think I agree entirely. There is no evidence iv injections of MSCs can help MS, despite the desires of these patients to find something more effective then what is currently available.
While I agree that patients desiring these therapies are not to blame, I do blame providers who prey upon patients. They offer therapies they tout as helpful, with no evidence this is the case. I wish there was some better way to stop these dangerous quacks.
Remember, another risk to patients is that is they get this MSC therapy is they would like then be ineligible for other trials but reputable investigators that could be helpful and are done is a proper (controlled) clinical trial.
Thanks for the comment, Dan. I have done a post in the past where I mentioned possible future trial exclusion–this might be of interest you:
https://www.ipscell.com/2012/12/eight-simple-reasons-not-to-get-an-unlicensed-stem-cell-treatment-3-exclusion-from-future-clinical-trials/
Paul