To me, following modern MS research progress is as exciting of an inward journey as space exploration is an outwards one. In fact to the point where I have considered leaving the tech field within the next 5-10 years to partake in it so it's fun to see this here on HN.
Just 20 years ago the first disease modification treatments were introduced. These were recurring injections of interferon-beta (1b/1a) for a 18-38% reduction in relapses and annual relapse rate (ARR) of 0.256[1]. Today there are about 20 different options, with Rituximab and humanized variants indicating an annual relapse rate of 0.044 for RRMS patients with a well understood safety profile[2]. On such medications an MS patient can expect a relapse every 22 years vs every 2.5 years unmedicated.
My pet theory is that MS research will ultimately lead to significant breakthroughs in longevity research. This is based on the morbid view that the disease is serious enough for risks to be taken in understanding auto-immune responses, crossing the blood brain barrier and remyelination.
As someone with NMO and on rituximab ... I'm all for you joining the many, many people working on these conditions. You have no idea how thankful I was to everyone that has worked in this field (and fought for funding in this field) because only a few decades ago my prognosis would have been MUCH worse.
The author of the diet herself seems to acknowledge that it’s very much unproven. I very much doubt there’s more to it than “unhealthy overweight people do better if they lose weight and eat more healthily”.
Personally I’ll stick with treatments that have have had their efficacy well proven through rigorous medical studies rather than ones designed to sell hope on amazon.
I’m not convinced these diets work as advertised..
I’ve read tons of scientific papers and there are too many contradictions.
For example these diets tend to forbid gluten intake, but some research imply better outcomes for patients with high whole grain intake.
I’ve also read that inflamation is useful for preventing cancer, so what good is not having relapses when you get cancer from all the anti imflammatory stuff..
> I’ve read tons of scientific papers and there are too many contradictions.
Dietary science is full of contradictions, and sometimes contra-indications.
There seems to be a lot of focus on some sort of mythical one size fits all diet for everyone. As if everyone's body systems would react in the same way to any given diet and with an assumption that you can rigidly control the ingredients in your food while still getting food from the grocery store and possibly restaurants.
When evaluating diets for conditions, I would suggest trying to figure out:
a) is it grossly unhealthy / what signs could I use to see if it is affecting my health negatively?
b) does it seem to work for some people?
c) is it something I could feel satisfied with for a long time?
d) how will I know if it's working or not? / how will I be able to confirm?
This is generally a smaller burden of proof than is there scientific consensus that it's a good idea. For many things that might have a connection to food, there isn't consensus on the mechanisms involved, and there may be multiple. It's plausible thst some mechanisms would be affected by diet, and others wouldn't, so some people would see good results by eliminating things, others would see no change, and others may have bad results.
> I’ve also read that inflamation is useful for preventing cancer, so what good is not having relapses when you get cancer from all the anti imflammatory stuff..
Chronic inflammation is a cause of cancer, not a preventative.
In theory if you’re comparing white bread eaters to whole grain eaters I’d imagine there would be a net benefit. I wonder if whole grain vs no grain has been studied.
I down-voted this comment for its tone. This is a thorough and well-informed rebuttal of the parent comment, but it's buried under an unnecessary layer of sass and sarcasm. I appreciate your passion, but we can do better than this.
People new to HN need to be introduced to the culture here without being deterred entirely from commenting again in the future. This way, others can engage the new user on the merit of their ideas (right or wrong) rather than on their tone.
Generosity notwithstanding, the comment did contain a grain of truth (heh) in that a good strategy for cutting through the contradictory tendency of dietary science is focusing on what works for many people in practice. (At least, that's what I remember; it's flagged now so I can't read it anymore.)
I’m comparing specific AIP recommendations with research which might have other recommendations.
In this case eating the (sometimes 10xmore) expensive gluten free, “everything free” foods vs eating “normal” foods.
After reading results which show that eating whole grains gives better outcomes measured on the EDSS scale in the same period of time compared to eating white bread or not eating bread at all, what am I supposed to think?
The “normal” bread industry is funding science to opress the gluten free crowd?
And gluten is just one tiny piece of this puzzle.
My point is that I’m leaning towards reading about as much factors which play a role in my wellbeing, and then weighing my options with some kind of understanding about how they work, instead of accepting one size fits all solutions.
Are you deep in biology like with a minimum BS or higher degree? If not, might just be too difficult to understand the value of the ideas. The lady prescribing the Wahls protocol is an MD so has a lot more invested into the field than the layperson. That said, she could still be wrong.
One thing is for sure, there is no one-size-fits-all and there is no magic bullet. If there's something helpful for one condition, it's probably harmful for another. The body is a complex holistic system after all.
Dr.Wahls has been disingenuous about her recovery because she downplayed her chemotherapy and the expensive e-stim therapy she received, which is not covered by insurance, and chose instead to focus her promotion and communication on something she could commercialize - her diet. M.S. patients like myself who do not have six figures to spend on e-stim are generally better off focusing on creating an optimal diet that positively impacts their microbiome while maintaining a normal BMI and exercising at a comfortable level.
Personally, when people think we are making good progress on something, I’m reminded of these words:
“Before this decade is out...”
Sure, great and rapid progress might require a couple percent of US GDP, and a million people working on a problem, but advancing medical research a few decades in the next 10 years, would benefit everyone.
The thing about clinical trials, is there is a minimum time it takes to run one. You can up concurrency but it only gets you so far - you really need to know the long term impact before you can iterate much.
The thing is honestly, we make incredible progress every decade. What's important is doing it carefully, correctly, and investing in the right areas to make real positive change (less viagra and hair loss probably).
Just a decade ago, Hepatitis C wasn't curable in nearly 100% of patients (in 12 weeks with limited side effects!). It isn't great news cycle content to focus on rehashing the great achievements we have recently made.
It's heartbreaking to have such a methodical approach for sufferers now of course.
I work in the industry and I agree we make remarkable progress now. And for some technologies like CAR-T and gene therapy, we’ve just started.
Your HCV example is a great one. Before the anti-virals, it was interferon. You had to take it for months and from talking to people, it makes you feel like you have the flu...for months. The label actually describes a risk of suicide. It’s a very rough drug to be on and the cure rate is <50%. And that’s if you stick with it, which many people don’t.
Today, we have regimens that are weeks in length, minimal side effects and 99% cure rates across all genotypes.
You’re talking about going from a very difficult to cure, chronic condition that can lead to liver failure or liver cancer to just being cured after 12 weeks.
I'm reminded of the joke between the cardiologist and immunologist...but the story of MS therapies goes hand in hand with the revolution in molecular biology - and by extension, immunology.
While it is sad that this drug cannot continue for MS directly, I love that this is science work at its best.
Experimental drug, through the efforts of terminally ill, are able to discover/show/validate quite powerful benefits, but the drug is too dangerous to use itself. So we stop it.
It is progress and many times, progress is not easy nor cost free. Thank you to all those who, even in their terminally ill state, helped progress treatments for others.
One thing I’ve always wondered is: how many drugs have we rejected like this, which were actually bimodal in their safety profile, the way many drugs are bimodal (or polymodal) in their effect profile.
I.e., that there’s some inherent difference between the people the drug harms, and the people it doesn’t; and if you can identify that difference, and test for it, then you can safely give the drug to only the people it doesn’t harm.
The way we currently investigate drug safety in clinical trials doesn’t really allow for this approach. We only seem to do it when a drug is initially declared as safe; introduced into the market; and then we find that it has side-effects that clearly correspond to some subpopulation.
In this case, adverse effects from Bexarotene are virtually guaranteed, even at low doses. This study explored hypothyroidism in even low-dose Bexarotene and found 61 out of 66 patients exhibited hypothyroidism: https://pubmed.ncbi.nlm.nih.gov/30903705/
Bexarotene also significantly elevates cholesterol markers and blood lipids, which would accelerate heart disease and shorten lifespan.
The researchers aren’t simply dismissing drugs at the first sign of side effects. We have many drugs on the market with significant contraindications due to adverse side effects in specific populations, and doctors are generally well-informed about testing for these conditions and selecting only suitable drug candidates.
One of the things not mentioned about bexarotene is that it's very teratogenic. That makes it more difficult (but not impossible) to use it for women.
> Materials to support the Pregnancy Prevention Programme in women and girls of childbearing potential taking oral acitretin, alitretinoin, or isotretinoin have been updated. Oral tretinoin and bexarotene do not have a Pregnancy Prevention Programme in light of their oncology indication and specialist care setting. However, healthcare professionals are advised that these medicines are extremely teratogenic and product information should be consulted for contraceptive and pregnancy testing requirements when used in females of childbearing potential.
When used for cancer these side effects are very common (greater than 1 in 10) or common (between 1 in 10 and 1 in 100). Some of these are going to be mild and temporary. But some of them are serious.
> We only seem to do it when a drug is initially declared as safe; introduced into the market; and then we find that it has side-effects that clearly correspond to some subpopulation.
This exact thing happened with another MS drug: natalizumab[0].
It was originally approved in 2004, but later withdrawn in 2005 due to some cases of Progressive multifocal leukoencephalopathy (PML), an opportunistic brain infection that is often fatal. The manufacturer later identified a specific antibody for a virus (JC Virus[1]) present in ~50% of the population which correlated highly with incidence of PML after 1-2 years on natalizumab (~1% chance of PML vs ~0.01% of the normal population). tl;dr the blood-brain barrier maintained by natalizumab also prevents the body from killing the JC Virus in your brain, causing inflammation and eventually death or serious permanent disability.
It was then reintroduced but now patients must undertake regular blood screening (every 6 months) for JCV antibodies, and regular (~12 months) MRI scans to monitor for inflammation (though this is pretty standard with MS these days to look for changes in lesions).
My wife has a rare type of MS (tumefactive MS, ~3000 people in the US have it) and has been on natalizumab since diagnosis about 3.5 years ago with no evidence of disease progression. The story would've been wildly different if we were born 20 years earlier before these treatments came about, it's honestly amazing. Without modern treatments it's very possible she would've been confined to a wheelchair within 10 years of diagnosis, but instead her symptoms are only really noticeable upon examination by a neurologist.
My wife was in the same situation as yours and was under Tysabri for many years (10 I think). Then she got the JC virus and had to stop (she was given a choice but decided to stop).
She moved to Gylenia and so far so good (or at least as good as someone can be with MS).
When she was diagnosed 12 years ago it was the beginning of "modern" MS treatments. 10 years back and it would have been disastrous. In 10 years there may be wonderful advancements.
I feel that 100-12 years ago was a true milestone.
The drug used in this study, Bexarotene, is already approved for cancer treatment and available in the United States and Europe.
Using Bexarotene in cancer patients makes sense because the side effects are more tolerable than dying from cancer.
Using Bexarotene in Multiple Sclerosis patients doesn’t make sense if the net effect is a worsened quality of life (significant thyroid disease) and a shortened lifespan due to accelerated heart disease (hyperlipidaemia and hypercholesterolaemia).
> Metformin seems to work by rejuvenating stem cells in the central nervous system, which then go on to become myelin-producing cells called oligodendrocytes. These churn out fresh myelin to replace that destroyed by MS
I have small fibre neuropathy, which has left me with constant pain. There are basically no treatments available beyond pain control, except for maybe IVIG treatments (there have been some papers showing promising results, but it's a very expensive treatment, and the NHS will not pay for it).
This is the first I've heard about metformin rejuvenating stem cells - if anyone knows more, especially in relation to nerve damage, or has some starting points for further research, I've be grateful.
My mom has SFSN and my brother has CIDP. From what I've seen IV IG is the only treatment for this kind of condition currently available and, even then, it's not a permanent fix. My brother has had it several times and it saved his life but the side effects are horrible. There are some interesting advancements happening in the States using stem cell but it's still very early days and even more expensive than IV IG. Just due to the process involved it's hard to see it coming down in price all that much.
This result is particularly exciting since it sounds like it's a drug and not a bio-product like IV IG or stem cell therapy.
Also, sorry to hear about your SFSN. Hope you're doing ok.
I'm in the UK, and new treatments on the NHS happen very, very slowly. If they're as expensive as IVIG, if they happen at all, it will be a postcode lottery, and only available for 1 or 2 specific conditions, with several constraints. I very much doubt it will ever be a possibility for me.
I have chronic idiopathic axonal polyneuropathy (and several other chronic conditions) that have left me in near-constant pain (and at times with mobility issues, particularly the first year). It was initially thought to be possibly autoimmune in nature (I have two family members with 1 or more autoimmune diseases), but it was never confirmed.
I've been told that IvIG isn't even a good option for me, and in any case, I'm concerned about the at times severe side effects.
There are so many people around the world suffering from various forms of neuropathy, yet it seems to get relatively little attention. Some people are in wheelchairs, some in constant and severe pain, others lose control of their bladder or bowels, and some experience all of the above. Many millions of people worldwide. It seems like there would be a greater effort to come up with new therapeutics. At the very least, it's a huge market.
> except for maybe IVIG treatments (there have been some papers showing promising results, but it's a very expensive treatment, and the NHS will not pay for it).
I know this may sound hard to believe, but in some cases it's possible to get insurance to cover IVIG for aaSFPN in the United States, even though it's not yet FDA approved for that condition: https://www.karger.com/Article/Fulltext/498858#scrollNav-3-6
Otherwise, IVIG for SFPN is quite expensive just about anywhere.
I will try to get back to this thread with some resources but I would recommend as you are in the UK to look into clemastine/tavegil which you can get without prescription (noted in the article as about to be trialled with metformin) due to its action on P2X7 receptors/Schwann cells.
The ReBUILD doses were rather high though (10 tabs a day!). 1 tab would probably do it over a few months.
That's interesting. Just take care with that. There's some epidemiological evidence that anticholenergics like clemastine may possibly contribute to dementia:
The data suggest correlation, not necessarily causation, but at the least I'd carefully investigate the risks before taking any anticholergic in such high doses. I do understand (with my own chronic health issues) that even with the risk of dementia later on, it may still be a possibility, depending on the severity of current symptoms.
Thanks, I've never even heard of clemastine, and it's rare to find anything notable that doesn't require a prescription in the UK! I already take another gen 1 antihistamine at night (they are very sedating for me), so I guess could swap it for clemastine.
Now all I need to do is convince someone to give me a prescription for metformin...
Burying the lede a bit: the drug can’t be used because its safety profile is unacceptable, but the possible mechanism might be targetable by other future drugs.
Actually if they know the mechanism of action and receptor that it affects, they can run computer simulations of thousands of chemicals quickly. This method of simulating the 5-HT receptors was used to find 25i-NBOMe, an extremely powerful serotonin receptor agonist.
I think people assume that drug development is still slow. For many targets, the time from discovery to market is around 6-7yrs (per a big pharma VP I spoke to a few years ago)
But when drug discovery is a 4-6 year endeavor, knowing your site-of-action better and starting from a well-characterized template is worth its weight in gold.
Edit: I realize this might not be clear, but drug discovery is a separate paradigm from drug development. So, together they take around 10-13 years.
The entire 25x-NBOMe series was an unfortunate find (sociologically). Lot of people seemed to have a bad time on them.
That was David Nichols' lab at Purdue IIRC. I also believe that they had found other, even more potent derivatives, but refused to publish them for fear they would be used as chemical weapons.
The report had claimed activity at something like 1-10mcg range, which is real spooky when you consider the impact aerosolizing that could have on a room.
Well unlike LSD which is a partial agonist, 25i-NBOMe is a full, irreversible agonist that can be lethal in the event of an overdose. It really wasn't designed for use as a recreational drug.
It's history of discovery (as well as the 2C variants) was extremely interesting though.
I see your point as I thought it for a second as well. At the same time, MS is quite a well-known acronym for Multiple Sclerosis even among lay people (anecdata: I am a layperson and know no one who has MS).
I know this is a tech/curiosity forum, and that it might be confusing for a second, but I feel a bit "Black Mirrorred" if the acronym MS fully belongs to Microsoft on Hacker News. I'm against giving them that power when it's in conflict with a scientific concept such as Multiple Sclerosis as scientific thinking is part of Hacker News.
With that said, I'm fine with whatever the mods decide, I simply want the mods to have considered my argument.
I'm Dutch and we know it as MS, as we also call it Multiple sclerose [1], so I wasn't aware of that.
Good nitpick :)
[1] https://www.hersenstichting.nl/hersenaandoeningen/multiple-s... <-- I know that sourcing this is a bit much, but I figured that some of you non-Dutch speakers might feel whimsical enough to look at some Dutch text for funzies. Or maybe it's just me who looks at random texts of other languages O:)
> While bexarotene will not go into phase 3 trials for MS, the finding that the nervous system can be stimulated to resheath damaged neurons has given scientists fresh hopes for another trial they hope to launch later this year. That trial will monitor the effects of the diabetes drug metformin along with clemastine, an antihistamine, a combination that Prof Robin Franklin at the Wellcome-MRC Cambridge Stem Cell Institute showed last year could drive remyelination in animals.
That would be an amazing find if it works in humans. My wife was on metformin for many years (not for diabetes) before being recently diagnosed with MS. Coincidentally she experienced her first MS symptoms shortly after stopping metformin. We suspect that use of prescription steroids along with metformin might have been masking the onset of her MS for years and in an indirect way even delayed it slightly.
She just got her first half-dose infusion of Ocrevus, other half scheduled for next week. Ocrevus is such an amazing disease-modifying drug. It's very expensive but our insurance covers it and after the initial dose, she only needs one 3-4 hour infusion every 6 months. No other medication needed on a daily basis! Ocrevus helps ensure no new flare-ups happen anytime soon but it leaves her immunocompromised and there is no remyelination. If metformin + antihistamine end up producing even a little bit of remyelination that would be a game changer because she's young and has enough time to regain everything if it just involves taking a couple of pills daily.
Unrelated but just putting this out there since it's fresh on my mind - if you or loved one ever gets diagnosed with MS or equivalent, you absolutely have to be your own advocate. Best thing you can do in the US is to get an online fax# (I use redfax) and the Dropbox app. Scan every single medical document you get with the Dropbox app, convert it to PDF, and then fax it over to 100 places as needed. Also sign up for every single patient portal including Quest/Labcorp. Be sure to get a DVD of every imaging test (CT/MRI) and upload them for free to postdicom.com to share with anyone or to just see it yourself if curious.
It is a LOT of work and very stressful. But if you're technically savvy, you can avoid a lot of driving back and forth between testing, doctor, hospital, medical centers. And above all reach out to anyone you trust for assistance, even if it's just to pick up groceries. People can surprise you with their generosity.
It occurs more often in females (who have a stronger immune system), than males. That being said, my father had it. I've always known my father as being ill, having MS.
It’s kind of disappointing that this drug won’t be used as a treatment. I get that this drug has dangerous side effects but life with MS is terrible and the life expectancy is short 5-10 years.
I fully believe that for chronic life threatening diseases people should be allowed to try all sorts of treatments that would be deemed unsafe.
What you said about life expectancy is not that clear, so I will clarify: average life expectancy for MS sufferers is 5-10 years shorter than the norm, but this gap continues to narrow.
Oh. I was about to say, my doctor said median was wheelchair in ten years, not dead. The severity varies tremendously, I (as sometime with MS) can totally see people with recent major episodes trading. They might not get another MS attack for years.
Must have been a pretty bad side effect though, my first treatment literally resulted in me needing surgery. If that was better than nothing... I'm just going to guess the side effects are very serious. Most other approved MS drugs have some nasty side effects or another already, the bar must be somewhat high given what it's treating.
That's not the average now, though - especially not for someone taking medication. If folks ever even need a wheelchair, that is often temporary. It is so much more common to use other walking aids, if you need them at all. And this is still factoring in folks that aren't taking medications and are older and couldn't start on treatments early. This is all changing: People are getting diagnosed earlier than they were previously and started on modern treatments early on, which not only tend to reduce flares (in folks with Relapsing-remitting forms, the most common type) but they make flares less severe. All of this means as treatments get better and younger folks make up more of the statistics, the disability chances should still go down.
OF course, there are some folks that do better or worse. I have very few day-to-day symptoms and those are mild: I'm 42. Some folks get in pretty bad shape in their 20s.
As far as side effects: Some have a much higher chance of death. When that gets to high, they deem it unsatisfactory. I wouldn't be surprised if this was instead of or including a chance of being even more disabled or damaging heart/lungs or something else that shortens life.
I am male, which accelerates the progression. But that was what my doctor told me in 2012 for men, even if taking interferon (which I did). And the two big new ones since. I stayed basically great until 2017. But now both hands are mostly numb and my leg is numb. I've taken the best medication available at every opportunity. Now it's progressive. I'm 37 and was diagnosed and treated very early after just one mild attack.
Anecdotes. I know. Although my progression so far has been fairly in line with my first doctor's statistics.
Unfortunately, men are so much more likely to wind up with a progressive form of the disease. I'm really sorry to hear that it has 'leveled up' like this. This is one of those fears in the back of my head, though with women it becomes more likely after menopause. I truly hope it doesn't get you down too much anymore and that you are able to find some enjoyment in life despite all this.
I am lucky, mostly: I'm 42 and have a bit of fingertip numbness and get some electric shocks sometimes. I wasn't diagnosed until around 2 years ago, though I had ON in my 20's.
It is somewhat odd, though: My neuro first tried to put my fears to rest, assuring me that it wasn't the same disease as it was even 5 years ago due to the drugs available. I wish more of them worked on progressive forms as well, and I'm still hoping for some miracle - it doesn't have to be a cure, per se, but something that at least heals more often.
My doctor may have been blunt with me because I grew up with family that has it. I've known what it was since I was 5.
But my doctor says the same lately, not even dimethyl fumerate was out there yet in 2012 and the best drugs merely reduced the probability of an attack by a little under 50%. Several current drugs I think are more like 70% and way gentler to take. Still far from perfect though, I've gotten worse despite three very different medications. But with MS we're kind of just playing the odds, and that 70% is aggregated across all underlying causes. Mine is almost certainly genetic. Maybe one drug works great for genetic causes but badly for some say chemical exposure that triggered it. But no one can tell that's the case.
That seems like something that could be improved for sure, personalized medicine. But I also don't find it hard to believe that we'll be regenerating nerves in ten years, that seems entirely reasonable given how long we've been studying them and the tools now available.
Stress has never been proven to be a link, though it is often repeated. Being male does sometimes make things worse and males are more likely to have a more progressive form of the disease than females. (The vast majority of patients are females: I know they suspect an interplay of hormones creating different outcomes, but I don't know if they've proven it).
As far as progression, that is something that happens to some people. Some folks never have the relaspses and time in between and others, the disease turns into progressive form. If scientists haven't figured out why some are more progressive or why some folks' MS turns progressive, I highly doubt looking at one's own life is going to find a key to progression. I'm not the parent here, but I can't see the point in such a thing.
Oh, I thought the statistics were that half as many men as women have it. I don't know if I'd call that vast, though admittedly most people who have mentioned that they have it have been women. I probably just saw bad stats.
Like, yes, my life has been very stressful for years at a time. Those times weren't when it became progressive though, and good luck finding a control that has never had periods of stress and then doing statistics on them somehow...
I was more pointing out that males, when they get it, are more likely to have a hard time and more likely to get primary forms and the relapsing forms are more likely to turn progressive early on (women wind up catching up after menopause sometimes).
And yeah, everyone has stress. They thought that stress caused relapses at one time, though, but further research has ruled it out. They can look at folks that have had undue stress and look at timing of relapses vs times of major stress to see if the link is correct. The 'stress-free life' advice still gets passed around though.
I am not even sure if major things are improved by my medication because I have no idea whether it would be even worse without. I can't do statistics on that... I definitely can't guess whether it becoming progressive is because I've had a lot of stress and wouldn't want to mislead anyone by suggesting it. As far as I know it just tends to happen eventually.
Stress seems to trigger attacks and symptoms though, I don't think that part is controversial.
> with MS is terrible and the life expectancy is short 5-10 years
That's not true at all (edit: oh I see what you meant--see other comments). My mother was diagnosed before I was 5 and survived until my 30s. I volunteered some with the MS society and there were many man and women who had lived with for several years.
For most of her life, there weren't drugs like betaseron or avonex. Those drugs also had terrible side-effects. I remember listening to a much older woman with MS talking to my mom and how when she was younger she got onto some clinical trial, but got terribly terribly ill. She decided then she wasn't going to be a guinea pig.
The woman said her life slowed down, and she couldn't keep up with a lot of her old friends, but formed new ones. She kept on living.
My mother kept hoping she'd be cured and took treatments as they were approved. They had pretty bad side-effects, and they didn't reverse the existing degeneration, just attempted to prevent further damage.
If you're diagnose with something like this, your health decisions are your own and you should make them carefully. But no matter what you decide, keep living. Adjust your life, deal with your "number of spoons," and keep going as best you can, even as you watch your mobility be taken from you by your own immune system.
Warning: be wary when you read "MS treatment" in a news title. You need to look into what exactly is treated. I'll explain this further below at [1].
There's a slowly progressing form of MS, and a quickly progressing form of MS. I'm not sure of the medical names in English.
You can definitely become old with MS.
My father got the diagnose in begin 70s (1972?) and I was born in 1983. He passed away in 2015 due to complications of MS. The disease affected him everywhere. I mean, I never seen him properly walk, but he only ended in a wheelchair end of '00s. It affected his short-term memory. It affected his kidneys, he was on dialysis for about 6 years. Eventually due to other complications he got infections, ended up with an amputation. He never fully recovered from that. He got infections elsewhere, and half a year later passed away.
[1] My father always kept hope for getting a treatment. He tried a lot of (insane) diets back in the 70s and 80s. None worked. Treatment-wise, they can stop the disease from progressing, but the people who get that treatment who are first in line are youth and people with the quickly progressing version. My father lacked both these variables, so he down below on the list.
Now, from what I understand in this century there's been various medication which can severely slow MS progression down, or even (more recently) completely halt the progression. The challenge with MS nowadays is reversing the damage done.
> But no matter what you decide, keep living.
We decided to stop with dialysis because QoL (Quality of Life) was near 0. My father's body was done. He's always fought the disease, till that point, and he had the mindset you described. He had to adapt to his new limitations all the time. I grew up with a father who was cursing a lot, but had a strong will (I suspect he had autism, like I have).
What I'd argue you need to realize is go carpe diem _without_ doing stupid "YOLO" stuff. If the progression of the disease cannot be stopped) your QoL is going down, and you don't know exactly how it is going down (you may have some ideas though, and you get monitored by doctors). You can use this to plan things you still want to do.
I also want to add that growing up with an ill father affected me in some negative ways, but there's also a clearly positive one. I have compassion for ill people, for weaker people, for minorities, etc. I believe it is because of growing up with an ill father, because the rest of my family on my father's side (cousins most notably) is [IMO] weak in this.
Indeed. For those with an aggressive form of the disease, I suspect they might be willing to try it and trade MS symptoms for something else at least for a time. Still this is providing some hope that it's at least possible to reverse the damage.
The drug is already available on the market as a cancer treatment.
However, don’t underestimate the impact of those side effects. If the drug accelerates heart disease (hypercholesterolaemia and hyperlipidaemia are among the primary side effects) and causes thyroid issues, then it might very well have the effect of worsening quality of life and shortening overall lifespan.
This drug doesn’t appear to treat the root cause of MS, but instead shows some efficacy in reversing one of the downstream manifestations of MS. That implies it would have to be taken indefinitely or at least cycled throughout life.
I know people want to be free to try different medications, but in this case it would be shortsighted to trade one set of serious, life-threatening health complications for another that might actually be worse.
Bexarotene, the drug used in this study, is already approved and available for certain types of cancer treatment. The problem is that the side effects are severe. Severe side effects can be acceptable in relatively short term cancer treatment, but untenable for lifelong treatment in Multiple Sclerosis patients.
Specifically, the thyroid effects of Bexarotene are so common and significant that one study even recommended that patients be given adjunctive thyroid medication when beginning treatment, even when low doses are used: https://pubmed.ncbi.nlm.nih.gov/30903705/
Likewise, the effects on blood lipids are significant enough that patients are frequently forced to take statins during their course of treatment: https://pubmed.ncbi.nlm.nih.gov/29805374/
Assuming an MS patient would have to take this drug for a lifetime, or at least use it frequently, suggests that these side effects could worsen quality of life or even shorten lifespan more than MS itself.
Promising drug candidate, but no one should be rushing out to find a way to get their hands on a Bexarotene prescription just yet.
It's interesting that this drug is a Vitamin A derivative.
The structure is very close to another popular drug, Isotretinoin (Accutane), with similar side effects.
I imagine Accutane probably doesn't have this effect or we'd have caught it, but how wild would it have been if acne medication also ended up being the cure to MS.
Great news for MS, but doesn't myelin also play an important role in learning in general? If a safer drug can be found I wonder what role this could play in treating some intellectual disabilities? Or, if one tends toward a more dystopian outlook, a role in widening the gap between the "haves" and "have-nots".
L-carnosine is VERY promising for MS treatment. It's been found that carnosine levels are significantly decreased in both animal MS models and humans with MS. [1]
This [2] completed (results pending) small study will try to verify if supplementing with carnosine will help slow down the progress of or even reverse MS.
Unofficially, I've heard it was a great success. But let's wait.
Ive used L-carnosine in conjunction with zinc, l-glutamine, keto+IF to repair a serious aspirin lesion in my gut and it worked great. I've read that benfotiamine can also help with myelin repair but do not have the studies handy.
I am on Ocrevus myself to treat MS. I have RRMS. I've been on Ocrevus now for a little over 8ish months! I really like Ocrevus... haven't really had any side effects or infusion reactions.
I look FORWARD to more remyelination news and research!!!
Layman here. I can't find a report about this clinical trial, maybe I didn't try hard.
It is a phase II, in a phase II the goal is not to test the efficacy of the drug, it is to test the presence or absence of side effects.
A phase III role is needed to test if the drug is helpful to patients. It involves several hundred people to avoid statistical errors. Here there will be no phase III trial.
Another thing is that nerves can repair in the peripheral nervous system (PNS), but (until now) not in the central nervous system (CNS). If a drug can help nerves to repair in the CNS, it is certainly something revolutionary.
Actually there is a recent publication which hints that bexarotene reduced the number of pro-inflammatory microglia/macrophages while increased the number of anti-inflammatory microglia/macrophages in mice:
No, seriously, it really did take me at least a half second to figure out they’re talking about Multiple Sclerosis. A rather different MS. I would encourage everyone writing and discussing this subject to be more explicit up front, and then they can keep calling it “MS” later in the article.
One of my favorite jobs, network admin at Chiron Corporation. They managed to get beta interferon to mostly work as a treatment for some MS. The side effects were difficult, but I hope it helped some people.
I'm confused about why Bexarotene can be sold as Targretin to treat "skin problems"[1], but cannot be used as a potentially life-saving treatment for MS.
Is it that the dosages must be higher to treat MS?
It’s not just pedestrian skin problems. Your quote stopped short of the full context:
“Bexarotene is used to treat skin problems from a certain type of cancer (cutaneous T-cell lymphoma-CTCL).”
Bexarotene is an already-approved cancer drug. Cancer drugs often have worse side effects than normal drugs because they’re taken toward end of life, or taken to delay or prevent death. The difference is that MS patients would presumably need to take this medication over the course of their lifetime, as it doesn’t address the core disease.
If Bexarotene accelerates heart disease and causes thyroid problems, a lifetime of taking this medication might actually worsen quality of life and even shorten lifespan. Unfortunately, many patients desperate to improve the symptoms they know might rush to replace them with side effects they don’t yet know.
Drugs may only be prescribed for an approved set of diseases. Using a drug for a new disease indication without a study to back it up falls"experimental treatment". In other words, using a drug for an unapproved indication is doing scientific experiments on humans without approval which of course is unethical (and illegal). That said it's easier to get permission to use a new drug for a new disease indication if the drug has had previous clinical history of treating other diseases. At least in my country such permission is handed out on a case by case basis after the responsible physician has applied to the proper regulatory authorities.
Not so in the US. Doctors commonly prescribe drugs for off-label use. They are legally allowed to and don't need the government's permission. Insurance companies might not cover it, the doctor's employer might not allow it, and if something goes wrong, they might be sued, and their malpractice insurance coverage might be canceled, but the practice is widespread, legal, and ethical. There are just limits and risks to consider.
Emcell in the Ukraine has been offering fetal stem cells to treat MS and other "incurable" diseases for 25 years now; if treatment early enough then can stop progression and regression (undoing the damage) if not too far progressed.
The producer is working on another documentary as part of research Emcell is doing on treating infertility - via injecting certain stem cells into the testes.
Maybe you should provide evidence if it's a scam - countering their research, etc - e.g. Finding legitimate research from researchers who have used same process and fetal stem cells but couldn't reproduce the results; unfortunately you'll be hard pressed to find that research in part because very few places are doing research with fetal stem cells due to local laws due to religious-political stigma associated with fetal stem cells.
Obviously it's easy to label something a scam if you've not actually looked into the details and because "it sounds too good to be true."
Maybe watch some of the videos to see qualitative data from people treated to at least see that part of it if you're not going to dig deep into their research.
I just pointed you to a clinic in the Ukraine who 30 years ago initially did 5 years research before clinically offering fetal stem cell treatments for 25 years - where their research, and I'd recommend you read through their site + you can email to ask them for whatever evidence or 3rd party research by others they could point you to to satisfy you.
Edit to add: or even better for actual experiential learning - find someone with MS who's searching for non-harmful solutions and have them do it, be close to them before to know their quality of life intimately, perhaps go with them for treatment, and then be with them after closely to see how/if they have improvements that you can see + that they report.
I'm guessing you didn't watch the documentary on YouTube yet either - otherwise that's some amazing acting by patients and their local doctors. They have other videos on their site as well.
Anything's possible. But without much better evidence than these guys seem to be offering, I wouldn't touch them with a barge pole.
Your "even better" suggestion seems pretty ridiculous to me, by the way. "Want to know whether this thing that seems like a ghoulish fraud preying on people desperate for a cure is real or not? All you have to do is find someone with the disease they claim to be able to cure, persuade them to go and do this costly, risky, probably fraudulent thing, and see what they say about their quality of life is afterwards!" And even if they do manage to persuade someone to do that -- all they get is an n=1 single sample, which is pretty hopeless evidence for anything, especially for a disease like multiple sclerosis which commonly comes and goes in mysterious ways.
They state very bluntly that MS is an autoimmune disease... when did this become clear to mainstream science? I believe it is though, and I also believe that remyelination is always occurring but hampered in MS and even regular people. Taking away the inflammatory signal will result in remyelination without any stem cells in my opinion.
> They state very bluntly that MS is an autoimmune disease... when did this become clear to mainstream science?
A while. The primary symptom of MS, the demylination, is caused by the immune system attacking the myelin. The _why_ of the immune system's attack is still unknown at this point in time, but that it _does_ has been known since at least 1965, with Schumacher's criteria.
I don’t think it’s that settled at all, certainly not in 1965. Prineas in 2001 showed that MS progression may occur in the absence of immune cells and inflammation, for example [0], and people have complained of progression even when taking extremely strong immunosuppressants.
While involvement of the immune system seems likely, and certainly most treatments target the immune system, I don’t think causality has been rigorously demonstrated. It has however been a few years since I looked into it.
As an aside, ISTM quite likely that there may be several causes for MS.
I wonder how often science gets derailed simply because people are in the habit of expecting a single answer to their questions. We know that car accidents cause lacerations, although there are plenty of cases that happen in the absence of car accidents. Isn't it possible that MS is a symptom with multiple possible causes, any of which could set off a vicious cycle of nerve degeneration?
The scientists don't get derailed, but I get too many forwarded articles with silver bullets. One of my friends suggested intentionally getting stung by bees. This is magical thinking for a complex illness.
On the other hand, tecfidera had as the active ingredient a chemical I can buy from alfa aesar for $22 a liter. There's a lot of things that no one has studied yet I guess, for better and worse.
> Prineas in 2001 showed that MS progression may occur in the absence of immune cells and inflammation
MS researcher here. MS as an autoimmune attack is largely settled in mainstream neuroscience. The paper you cited does not show what you said it does.
From the paper:
> restricted largely to short segments of disrupted myelin located within linear aggregates of microglial cells
The paper is interesting because it shows that demyelination is happening in lesions that we thought were inactive, but actually do contain microglia and macrophages (immune cells) eating myelin (i.e. an autoimmune --immune system attacking self-- attack). The paper is paywalled but I but you can read it on sci-hub (https://sci-hub.scihubtw.tw/10.1002/ana.1255) Although just reading the abstract says the opposite of what you are claiming, the entire thing is about microglia and macrophages contributing to lesions that the researchers thought were inactive.
OK. I might be quoting the wrong paper, and I’m not a researcher, but I remember clearly that he found a case (14yo girl IIRC) who died during an attack, and there was no immune activity at the site of at least one of the lesions.
If I’m wrong about this then I will accept it, I don’t have an axe to grind.
MS is a catch all. Multiple causes can result in demyelination even if the mechanism is the immune system. You have MS if you have demyelination products detectable in your spinal fluid and have lesions on the spinal cord. Whether it's a genetic, environmental, or some other underlying condition clearly varies, for instance the version that I have is almost certainly genetic because of family history but plenty of other people get it with no family history.
But I think people are pretty sure that certain B cells are the easiest to interrupt culprit, my current medication literally just kills a specific B cell and that treatment last six months. Take from that what you will.
_Causality_ is unlikely to be demonstrated until a direct cause is known, and for a complicated illness like MS, it is likely to be a variety of factors, an active and changing area of research.
That in itself doesn't in any way mean that MS wouldn't be classified as autoimmune, however. If there is a high degree of immune system involvement, then it is generally classified as autoimmune, or immune-mediated. And that had been demonstrated. Such as in this [0] paper.
You seem to be well informed. Do you know if there are any studies on: if one suffers from one autoimune condition is he more likely to suffer from others?
I am in no way an expert, which makes me very hesitant to answer these sorts of questions. I am a random person on the Internet. Take that into account when you read what I've written, and weigh it very skeptically.
My knowledge comes from my own health. I was diagnosed with fibromyalgia (which is probably not an autoimmune disease. Probably.), after a ten year long process. MS was the other diagnosis being considered at the end of that process. If I had lesions, MS, if not, FM. Because the latter leaves no physical traces that can currently be detected (there is some progress on that front, but one study does not a trend make).
Some illnesses do have a likelihood to be co-morbid with others. FM for example, has a large number of illnesses it often masks, which may mean it is more likely to have that sort of comorbidity, or it may mean that the statistical model to work out if it is more likely to occur is extremely difficult to create.
I can't speak to whether a disease being autoimmune in nature makes it more likely to trigger other autoimmune illnesses, but it wouldn't be surprising to me. A malfunctioning immune system can malfunction in unexpected ways.
IME, many doctors, and even some consultants, use fibromyalgia as a catch-all where there is chronic pain and fatigue, but they can't find the underlying cause - basically a big umbrella to cover what are likely a broad spectrum of diseases and health issues.
I suffer from chronic pain and fatigue, and was previously diagnosed with fibromyalgia by both a rheumatologist and a neurologist, despite not even meeting the diagnostic criteria, and having an unrelated auto-immune health issue. Later on, via a skin biopsy I insisted on, it was discovered that I had small fibre neuropathy - damage to the small nerves responsible for pain signalling.
You didn't say anything about your specific symptoms, but if you have chronic limb pain, it might be worth looking at getting a biopsy.
> IME, many doctors, and even some consultants, use fibromyalgia as a catch-all where there is chronic pain and fatigue, but they can't find the underlying cause - basically a big umbrella to cover what are likely a broad spectrum of diseases and health issues.
That is very much not myself. I meet all the diagnostic criteria, and regularly experience somewhere around a hundred of the two hundred known symptoms. There is not another illness that matches my symptoms as well as fibromyalgia. I am a case study in what FM looks like at its very worst (literally, I've been featured in several journals as a case study).
I went through a variety of nerve studies before the diagnosis was made, and they're functioning perfectly. Including multiple biopsies. Getting the FM diagnosis is not easy where I live, most specialists would rather send you away with no diagnosis than that one. I met the criteria for FM on day one, and went through a decade of being tested for absolutely everything else.
The propensity for overdiagnosis, in some nations, of FM, causes me no end of pain whenever I raise the illness. There is always someone who feels the need to tell me that they believe it doesn't exist, or think that I must have something else that has gone undiagnosed, or think that they can suddenly cure it. That's exactly why I don't talk about it in detail. People think that they're helping, especially if they're empathetic. But all it does is undercut the last fifteen years. It makes the suffering more... Lonely. I can appreciate the sentiment, but I've never been able to appreciate the gesture.
I do expect that somewhere in the future FM will be split into several different types, and even illnesses. The illness is extremely "young", it got its name in 1993 (30-40 years younger than MS). Most of the illness is a total unknown at this point in time. There's no real global agreement as to what kind of illness FM is. It gets called autoimmune, neurological, rheumatoid, etc. depending on where you live. The evidence is currently leaning towards neurological, as FM has markers in the white matter of the brain that are unique to those who suffer from it. But we'll probably need another decade or two to be certain about that.
There is some mixed data, but the consensus is that MS is strongly correlated with other autoimmune diseases. This article has a good summary of several papers on the subject. You can scan down to the section on "Studies of Autoimmune Comorbidities in Multiple Sclerosis"
Just 20 years ago the first disease modification treatments were introduced. These were recurring injections of interferon-beta (1b/1a) for a 18-38% reduction in relapses and annual relapse rate (ARR) of 0.256[1]. Today there are about 20 different options, with Rituximab and humanized variants indicating an annual relapse rate of 0.044 for RRMS patients with a well understood safety profile[2]. On such medications an MS patient can expect a relapse every 22 years vs every 2.5 years unmedicated.
My pet theory is that MS research will ultimately lead to significant breakthroughs in longevity research. This is based on the morbid view that the disease is serious enough for risks to be taken in understanding auto-immune responses, crossing the blood brain barrier and remyelination.
[1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5474703/
[2] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5109942/