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Canadian doctors reverse severe MS using stem cells (vox.com)
371 points by yurisagalov on June 11, 2016 | hide | past | web | favorite | 77 comments

I live in Canada. I just listened to one of the participants talk about the experience on the radio and I found it just incredible.

In her own words, "She could not feel her body from the neck down. After the long and gruel ordeal procedure, she began to get sensation back. Things like hot and cold water began to be discernible. She no longer needed to hold both railings when walking down stairs in her home, needing a cane to get the mail, etc ..."

She said that it gave her her life back. She said that in short time, she began to get bored with doing the regular, tired routine and actually got a part-time job.

I mean, all that sounds phenomenal.

It does sound phenomenal, but bear in mind there was no placebo control, so we don't know how much of the effect was due to the placebo effect.

Generally the placebo effect will vary depending on the type of intervention. A very novel and invasive intervention like this will have a high placebo effect. Remember Liberation Therapy?

Given that psychological treatment alone can reduce the fatigue in MS to below that of healthy controls (van Kessel 2008), it's likely that the placebo effect plays a large role. (The placebo effect will also affect pain, weakness and numbness, as the part of the brain that produces fatigue - the anterior cingulate cortex and insular cortex - also produces those symptoms).

Hang on a minute.

Placebo effect does not explain regaining sensation, nor regaining ability walking.

Sure it can. Sensation is a subjective measure by the patient themselves. If the patient takes a drug then you ask if sensation improves, they could certainly say "it feels like it's improving".

And with regards to ability to walk, fatigue is often a major complaint in MS. If the patient takes a drug, "feels better", they may have more energy and do better on a walk test.

There are measure where a placebo effect is unlikely, such as blood tests of biomarkers or physical processes that are easily measurable without having to ask the patient (e.g. plaque buildup on arterial walls).

I think you're vastly and grossly underestimating how multiple sclerosis impacts your nervous system if you think that a placebo effect making you "feel better" will give you the ability to walk again.

It's actually a little stunning, reading your position on this.

It's not my position, it's the FDA's position. Take a look at some of the FDA's comments on other disabling diseases like Duchenne's muscular dystrophy. An improve in an ability to walk (6 minute walk test, 6MWT) is view with skepticism by clinicians.

For the purposes of clinical trials, are there any conditions that are excluded as possible placebo effects?

Regrowing limbs for an obvious start. Placebo is mostly effective with pain and has minor impacts on other issues.

That's exactly the placebo effect. You think that you get a treatment and your body reacts to that

Also MS in particular is famous for misleading results due to spontaneous partial remission unrelated to the treatment.

Placebo effects don't last 15 years.

They certainly can if the initial illness is psychosomatic. I'm not saying that is the case here, but I've certainly seen people with identical symptoms fully recover from psychological treatments. There does appear to be a certain psychosomatic aspect to MS, given how effective CBT is in treating the fatigue, the fact that it is triggered by stress, and that depression is a major factor in MS (and plaques appear to be correlated to depression rather than to disability).

I could see that if it was a pill or injection taken periodically over 15 years, but not a single procedure. In general, you have a point but the fact a single procedure has been curative for 15 years suggests with high confidence that there is real effect.

Also claiming that MS is largely psychological is, at best, insulting to MS patients.

>I could see that if it was a pill or injection taken periodically over 15 years, but not a single procedure

This is a pretty involved, and long, procedure. One of the main factors about psychosomatic fatigue/pain illnesses is that the patient gets stuck in a vicious circle where the stress of the illness itself causes further symptoms. Sometimes all that is required is something that breaks the cycle.

>Also claiming that MS is largely psychological is, at best, insulting to MS patients.

First of all, I never said that. I pointed out there there are psychological aspects to it, and argued that there may be some patients diagnosed with MS who have a psychosomatic illness. What % that is, we don't know.

I would also argue that it is very unhelpful for you to have that attitude, and it is a reflection of the bias against psychiatric illness that is so prevalent in society.

It also goes against what we know about how the brain works. It has been pretty conclusively demonstrated by Noakes and others that psychosomatic fatigue is a fundamental part of the human brain, and likely all mammals as well. Saying that psychosomatic symptoms are somehow bad - or imaginary - is fundamentally misrepresenting the science.

Unfortunately this is a very common attitude. I saw last week one of the world's top medical researchers say that changes in mitochondrial activity prove that an illness is not psychosomatic. That statement is, of course, demonstrably false, because cortisol (and therefore stress) reduces mitochondrial activity.

MS is nerve damage caused by the nerve cell's coating (Myelin) being mistaken for a foreign body by the immune system, and attacking it. How would the Placebo effect stop and reverse that nerve damage?

Placebo would have no effect on that nerve damage.

Some of the symptoms of MS have nothing to do with the nerve damage. Some of the symptoms are real, but not explained by the MS. Those symptoms may be relieved with psychological therapy.

They use CBT for pain in some cancer patients - use of psychological therapy for real symptoms in people with physical illness isn't a bit of woo-peddling. It's giving people in pain some help.

>MS is nerve damage caused by the nerve cell's coating (Myelin) being mistaken for a foreign body by the immune system, and attacking it.

That's the headline theory for MS, but if you look at the actual research you'll see that it's not actually proven. Sensitivity and specificity are 46% and 63% for the McDonald criteria, which is very poor. Plaques in MS are associated with depression, not disease activity in general. Patients with depression (but no MS) show myelin damage and brain plaques as well. The myelin damage may just be a factor of depression.

Sometimes things in medicine aren't quite as settled and proven as you might think. MS is certainly a very good example of this. Unfortunately there is such emotional and intellectual attachment to the idea that MS is neurological and caused by myelin damage that it is next to impossible to change people's minds. (I'm talking about the minds of doctors and researchers, not patients). It's certainly not something I'm interested in doing. I just find it interesting.

(I might have entirely misinterpreted your comments, but they're definitely thought provoking -- and I only have more questions)

Are you suggesting that there might be 2 or more diseases that present as MS, some of which might be psychologically caused? If this was true, is there a process to look for this? Or that we don't know anything at all about MS since 'its' effects that we know to look for could be caused by the depression that comes with a debilitating condition?

Is there a point where if a costly placebo grants amazing results, is it was worth 'going through the motions' anyway to save lives \ greatly improve the quality of life?

[reply deleted due to downvotes]

I guess this isn't the place for logical discussion. You post a logical, well-thought-out reply based on science, and people just downvote it. Discussion over. Sadly, this obviously isn't the place to discuss innovative research like this.

Sounds like another good reason to consider banking stem cells, as described here: https://news.ycombinator.com/item?id=11830407

In this case the article describes using chemotherapy to stimulate generation of stem cells, then scrubbing them of the disease before reintroducing. I have no expertise in this field, but I would think having a bank of healthy stem cells would have simplified the procedure and perhaps improved the likelihood of positive outcomes.

@markkat if you're reading this, do you have any comment?

>I would think having a bank of healthy stem cells would have simplified the procedure and perhaps improved the likelihood of positive outcomes.

It is possible, assuming that the banked cells were drawn before progression to a disease state. Here, they used the patient's own cells, which they treated before reintroduction, which strongly suggests there is a state to which they can be reverted. It's reasonable then to assume that at the very least, previously banked cells could be similarly treated before reintroduction, which might be a better starting point.

As speculated in the article, those patients that did not respond might have progressed too far for the treatment to work. If so, cells banked years before might be advantageous. Of course, that may not be reason why those patients didn't respond. Much of MS still remains a mystery.

Still, these results are very exciting, and add to the growing evidence that bone marrow stem cells have real clinical potential.

I'll ask our Chief Science Officer, Dr. Ben Buller, to discuss this trial in our blog: http://foreverlabs.co/blog He has published work using bone MSCs to reverse demyelination, which occurs in MS. I'm sure he'll have some good perspective.

In the study, the patients' immune systems were cleansed of the agent or agents that caused the autoimmune response. The agent might be present from birth; no one knows what it is, even today. Thus, unfortunately, banking stem cells and restoring them to the body might have the opposite effect of a cure.

If they can figure out how to isolate only the specific agents that trigger the attacks on myelin, that would obviously be a huge step forward.

That all happened 15 years ago. The article mentions that it's available at some hospitals, so that suggests it was ultimately successful and it's now part of regular medicine. I suppose it's still only for 5% of cases and only as a last resort and still most patients aren't having any reversal of their disease. There doesn't sound like much hope for it to expand to cure MS in general given how long it's been with apparently no further progress.

> still most patients aren't having any reversal of their disease

From the article, "70 percent saw the progression of their disease halted or reversed"

70% change of no further progression or even reversal? Those are good odds.

I was just stating the outcome in a more negative way. Most had no reversal but also most didn't get worse either. Because half of that 70% were in the "halted" category which might not be much use if you're already at a late stage of the disease and you were only eligible for this treatment because you were almost dead.

"One patient died, which puts the potential for death from this procedure at around 4 percent, and severe infections after stem cell treatments — the kind Molson picked up, or worse — are also common."

That was patients in the study, the comment was about all patients with MS.

This is the tech support approach to the immune system:

Try turning it off and on again.

A corollary of which is that the immune system runs on MS Windows.

Given its baffling nature, I'd say that's a pretty apt comparison.

Just in case anyone is wondering -- though at this point, isn't it your first guess? -- the stem cells used in this therapy were adult stem cells, meaning they were collected from her own body, as opposed to embryonic stem cells.

I mention it here because the article doesn't give that info until about half-way down.

I don't understand why you felt it necessary to mention this. I think it's half-way down in the article because it's not really the most important aspect of the conversation.

I think the fact that MS has been cured in some people for the first time is far more relevant than the source of the stemcells used to cure MS.

Simply recalling days where there was a big bugaboo over the source of stem cells and how many were claiming that research would be forever stunted without full access to embryonic stem cells.

While it likely did impact several promising areas of study it did end resulting in good research being performed in the field with what they could easily and without controversy obtain.

Oddly while some outside the field attempted to limit the areas of research some inside were unintentionally limiting themselves as well

I don't understand why you don't get it. There's a long history in the United States where people are strongly against funding stem cell research.


People who don't understand the political climate are hindering science because of various groups. We could probably be a decade farther in research if more money was available for stem cell research 20 years ago, for example.

> There's a long history in the United States

Headline: Canadian Doctors.

Americans can hide themselves away from the world in made up religious ideas, the rest of the world will get on.

Please don't be dismissive and shallow on hn. This is not Reddit.

I take his point to be substantive: if Americans continue to tolerate the religious right's war on science, we will continue to fall behind the rest of the world.

We're getting off track. America does a tremendous amount of the medical (and otherwise) science that helps progress modern medicine, and here we have a documented use of stem cells with an incredible outcome that is not encumbered at all with controversy. This is a win, no matter how calous you want to be about America. (New flash, religion affects the political climate all over the word.)

It is not a 'war on science' to oppose killing embryos for their cells any more than it is a war on science to oppose killing prisoners for their organs. Science can only answer the question of what will happen if one does one thing or another; religion/morality/philosophy must answer the question of what should happen, which implies what one ought to do.

Save for psychopaths, everyone applies some sort of moral calculus to his actions.

The religious right does comprise the largest portion of those who recognise the scientific fact that an embryo is a living human being and apply the moral principle that killing innocent human beings should be avoided (much as the religious right comprised the largest portion of those who recognised the scientific fact that blacks are human beings, and applied the moral principle that human beings ought not be enslaved, 150 years ago). It's not a war on science; it's applying moral principles to scientific facts.

This comment will be interesting to look back on in ten years if Trump wins.

We can be pretty bad here in Canada in fact my province has just made abortions legal here in this province this year 2016.

Technically abortions were legal for years but you had to leave the province drive two to four hours plus a $50 road toll, plus fuel, time off work etc.

I'm not female and never been in a situation needing one but I think it's about time it was allowed here.

So yeah the people here would probably be very vocal about stem cells at all still today. Any who knew of stem cell history would probably still assume they were fetal sources or just not care and protest anyway.

Haper is/was about as anti-science as they come, no matter his motivations for being so. Canada isn't some pancea of unencumbered science.

> Canada isn't some pancea

I did not say, nor did what I did say imply, it was.

What I replied to was putting an American debate forward as a global issue. What American policy makers do has very little to do with what research occurs in other parts of the world.

Once again, that I said the USA is deficient in one regard does not mean I am saying the rest of the world is better in every other, or even any other regard.

Well, a rather large part of the country want nothing to do with embryonic stem cells as they are linked directly with abortions. Non-embryonic stem cell research is pretty much only opposed by a small sliver of the population (generally the type that opposes everything). Treatments that use your own body as part of the cure are widely accepted as fine (well, expect by the FDA, but that's another article).

You can get a lot of non embryonic stem cells from your own placenta and cord (if it was kept). Had the cells been embryonic I wonder how many of the anti choice crowd would have changed their views.

Yep, and I've seen women keeping those for that purpose (have no idea about how the long term storage is accomplished). Probably all of the anti-choice crowd, would be a bit hypocritical to change view. They would regard it as trading souls for souls.

I wonder who owns a placenta - child or mother? Presumably it's only handy to the child.

Well, I understand that it is handy for the mother in dealing with depression. I don't have the literature handy.

Depends how you feel about stem cell research.

I feel like it's been held back for a decade or two by, mostly, the religious right, and I wonder how many people's lives are worse off as a result.

Why was it held back? The only legislation passed was around gov't funding of new embyonic stem cell lines. Private money has no restrictions.

I wonder how many more lives would have been ended had federal dollars funded research using embryonic stem cells.

The religious right (US-version):

Life begins at conception and every life is special.

Also for: guns, more prisons, war on drugs, war on terror, global warming does not exist, borderline racist social policies, george bush jr., "doesn't trust science", lack of financial success can only be the result of personal failings (and choices), and no taxes because "who needs roads" and "I did it all myself".

Not saying you (PP) share any of those, but why is it that the supposed humanitarian group when it comes to embryos tends to treat actual living members of society so poorly?

Meanwhile, the bleeding heart liberals are all baby killers (or at least, there's a rather large distinction between embryos and babies, in their opinion).

Serious question, isn't that a weird dichotomy?

A group who actively works to convince others they are victims is treating others poorly.

I long for days when it won't really matter how you feel about stem cell research.

Just as important for USA readers is the line "They then hooked her up to a machine that cycled through her blood 32 times over the course of seven hours, in order to collect stem cells. Those stem cells were then purified, wiped of any memory of the disease, to later be transplanted into Molson through a blood transfusion."

Our FDA has been making life a pain in the butt for anything that takes stem cells from a person, processes them, and then puts them back into that person.

Not just the FDA, but the EMA in Europe as well. "Non homologous use" or "substantial manipulation" makes it an ATMP (advanced-therapy medicinal product): http://www.ema.europa.eu/docs/en_GB/document_library/Scienti...

Quite interesting. But something i don't understand, MS causes immune cells to attack the myelin cells. Depending on the severe of the attack the myelin cells are completly destroyed or even the nerv cells themselves are destroyed. Recreating the immun cells would prevent the immun cells from attacking the myelin cells, but what happens to the tissues which are already destroyed? As far as i know, the body is not able to repair all kind of destroyed nerv cells / myelin cells on his own. So how can this treatment help to repair/recover already destroyed tissue?

A similar (smaller) study was done back in 2003 with Crohn's disease. The results were similar.


A more recent, better controlled study found very little difference between traditional treatment, though.


Related; Type 1 diabetes being also auto-immune disease. There have been now atleast 2 groups that have succesfully done "cure" using same kind of immune system reboot strategy.

few interesting links;

[1] http://cureresearch4type1diabetes.blogspot.fi/2008/12/burts-...


[2] http://cureresearch4type1diabetes.blogspot.fi/2010/11/snarsk...

> And there are questions about the very long-term effects. It’s not clear what the next 10, 20, or 50 years look like for patients like Molson.

Does that even matter? Molson would probably be dead right now if it weren't for the treatment, not to mention an enormous increase in quality of life. Even if the treatment kills her in 10 years, she will have had 25 years of a proper life, versus a few more years of lying in bed.

Of course long term effects are interesting to study and see if there is room for improvement, but I don't see them impact the validity of the treatment.

There was a comment on this on BBC breakfast yesterday, with an MS specialist saying that it was promising, but not up to the hype that people were making over it? He said it was an Avenue to explore further, and looked to be a good technique, but there was a long way to go - he quoted the stats from the study, and certainly seemed to be familiar with it and the methodology used. Can't find a link to it (it was an interview rather than a feature), alas.

My Dad had MS and died earlier this year of pneumonia. MS is a horrible disease in every way. It's debilitating, humiliating, and painful.

Hopefully this study can be repeated. So many studies using whatever is the trendy science of the day end up failing. This study looks hopeful and could be life changing in the best way possible. But it's not the first study that has started with an amazing result.

Publicity materials: http://www.eurekalert.org/pub_releases/2016-06/tl-tln060816....

Paper: http://www.thelancet.com/journals/lancet/article/PIIS0140-67...

The latest update for ongoing efforts to test destruction and recreation of the immune system in patients suffering from the autoimmune disease multiple sclerosis demonstrate that this approach is effectively a cure if the initial destruction of immune cells is comprehensive enough. Researchers have been able to suppress or kill much of the immune system and then repopulate it with new cells for about as long as the modern stem cell therapy industry has been underway, something like fifteen years or so. Methodologies have improved, but the destructive side of this process remains unpleasant and risky, something you wouldn't want to try if there was any good alternative. Yet if not for the scientific and commercial success of immunosuppressant biologics such as adalimumab, clearance and recreation of immune cell populations may well have become the major thrust of research for other prevalent autoimmune conditions such as rheumatoid arthritis. Destroying these immune cell populations requires chemotherapy, however, and with avoiding chemotherapy as an incentive for patients, and the ability to sell people drugs for life as an incentive for the medical industry, biologics won. For conditions like rheumatoid arthritis, the aim became control and minimization of symptoms rather than the search for a cure. Only in much more damaging, harmful autoimmune conditions like multiple sclerosis has this research into wiping and rebuilding the immune system continued in any significant way.

It is worthy of note that while these trials were only enrolling a small minority of patients, the approach could be used on every patient. That tends to be the way trials work, picking a small subset. The driving factor for keeping the numbers small is the onerous and risky chemotherapy process.

Beyond being able to pinpoint which tissues are suffering damage due to inappropriately targeted immune cells, the underlying mechanisms of most autoimmune conditions are very poorly understood. Multiple sclerosis, for example, results from immune cells attacking the myelin sheathing essential for proper nerve function. Collectively, the cells of the immune system maintain a memory of what they intend to target, that much is evident, but the structure and nature of that memory is both very complex and yet to be fully mapped to the level of detail that would allow the many types of autoimmunity to be clearly understood. That these autoimmune conditions are all very different is evidenced from the unpredictable effectiveness of today's immunosuppressant treatments - they work for some people, not so well for others. Many autoimmune diseases may well turn out to be categories of several similar conditions with different roots in different portions of the immune system.

Destruction of the immune system offers a way around present ignorance: it is an engineering approach to medicine. If immune cell populations can be removed sufficiently comprehensively, then it doesn't really matter how they are storing the bad data that produces autoimmunity. That data is gone, and won't return when immune cells are restored through cell therapies. The cost of that process today is chemotherapy, which is not to be taken lightly, as the results presented here make clear. A mortality rate of one in twenty is enough to give pause, even if you have multiple sclerosis. In the future, however, much more selective cell destruction mechanisms will be developed, such as some of those emerging from the cancer research community, approaches that will make an immune reboot something that could be undertaken in a clinic with no side-effects rather than in a hospital with all the associated damage of chemotherapy. Autoimmune diseases are far from the only reason we'd want to reboot our immune systems: as we age, the accumulated impact of infections weighs heavily upon the immune system, and its limited capacity fills with uselessly specialized cells rather than those capable of destroying new threats. Failure of the immune response is a large part of age-related frailty, leading to both chronic inflammation and vulnerability to infection, and it is something that could be addressed in large part by an evolution of this approach to autoimmune disease.

Does this teach us anything about the causes of MS, and potentially inform on preventative measures?

A nice longterm study. However, the fact that they need to specify in the title of this lay article that "this isn't hype" really says it all about science "journalism."

Also the fact that if you read the study, it IS hype. (fromory, because I'm mobile) One study, of 24 people. The treatment is only for 5% of MS sufferers, and it's 70% effective at stopping the progress of the disease. Only 3 of the patients in the study had a reversal like the case they describe, so 12%. And the treatment is incredibly rough on the body. One person in this study died from treatment, but almost everyone else suffered at the high end of the scale.

The not hype version would be "Potential treatment for 3% of MS patients in extreme risk cases! It even reverses the disease for a lucky handful."

It is a bug advance, but... Well this is Vox, after all.

The 5% was for eligibility, because other treatment options had been exhausted for that group - but presumably it could be made available for a wider range as well. Due to the intensity of the treatment the other 95% may opt for a different path.

The treatment is definitely rough on the body as they appear to wipe out the entire immune system via chemo, but the person who died did not die from the treatment itself.

The number of patients experiencing some sort of reversal was 8 out of the 24, or 33%. There were also 7 (I believe) who had the progress of the disease halted. The last 8 did not see the progress reversed or halted, but I was unclear on whether it progressed at the same rate or not. Regardless, it would seem that at least 70% of the participants saw a benefit.

They did also mention that of the 8 that did not see a regression or halt they believed that the cause may have been the timing of the treatment and the prior progress of the disease in those patients. I wonder if the treatment could be started quickly enough if it would be possible to see a regression in a higher number of cases?

Anyways, I wouldn't say it's really hype in any way. There's clear results, and they can likely be improved on to increase the efficacy and availability for those who suffer from MS.

Well the title wasn't "MS universally cured". It's significant progress towards a cure. And curing 3% of a disease that afflicts millions of people is still tens of thousands of lives saved.

And, more interesting, I think, it confirms the theory of what cause the illness. That was not so clear the last time I read about it.

That in itself is a big advancement.

The Lancet article says that one patient died of complications with the transplant procedure, and this was Phase 2. I'm in pharma, not stem cells, but if a patient died due to treatment, the project would be killed. Perhaps the transplant procedure is well-understood along with its risks (I assume you have to transplant into the CNS?), but even oncology drugs aren't allowed to kill patients anymore.

No, not into CNS. It is a well established procedure, is more than a little rough. "Those stem cells were then purified, wiped of any memory of the disease, to later be transplanted into Molson through a blood transfusion."

> Only 3 patients in the study had a reversal

It was actually 8 of the 24 that saw recovery so that's 33%.

Thank you for your diligence.

At this point I'm surprised there aren't Science Researchers with Giant Gold Clocks around their necks to promote a new paper they're spinning.

I believe this might have been the study where 25%(?) of the patients were killed by the treatment. As a result, this is only indicated for the very severe RRMS (relapsing-remitting, not related to Stallman) cases.

I'm sure HN can correct me if I'm wrong, but the point to make is that this isn't a cure.

Maybe you can read the article and correct yourself?

1/24 patients died during the trial (no causal link was specified), and the treatment was given to progressive MS patients (PPMS or SPMS).

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