14 ms·

MS treatment a step closer after drug shown to repair nerve coating

491 points by pujjad 6y ago

bognition 6y ago
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.
- thowaway1001 6y ago
  It mat not be only the safety profile, but also the fact that drug patent has expired in 2016. I am sure they’ll come up with an alternative that may have similar or better safety profile and could pay for clinical trials. No company is going to finance Phase 3 trial on patent free drug.
  - justinclift 6y ago
    Are you meaning the expiry of the 1999/2000 patents? There seem to be several others, including some filed recently: https://www.drugpatentwatch.com/p/generic-api/BEXAROTENE https://www.drugpatentwatch.com/p/generic-api/BEXAROTENE On a side note, is anyone aware of better info source that "drugpatentwatch.com"? That site seems to lock useful info behind a paywall.
- james_pm 6y ago
  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.
- hardlianotion 6y ago
  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.
  - neltnerb 6y ago
    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.
    - Broken_Hippo 6y ago
      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.
      - neltnerb 6y ago
- kzrdude 6y ago
  How the disease hits is widely different and this generalization is incorrect - it might get some sufferers correct, but far from all. Source: friends with very normal lives
- djsumdog 6y ago
  > 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.
  - Fnoord 6y ago
    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.
- PragmaticPulp 6y ago
  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.
- deleted 6y ago
  [deleted]
hprotagonist 6y ago
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. Translation: come back in 2040.
- TheAdamAndChe 6y ago
  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.
  - epmaybe 6y ago
    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)
    - whymauri 6y 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.
  - gavinray 6y ago
    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.
    - TheAdamAndChe 6y ago
vwat 6y ago
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.
- shakna 6y ago
  > 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.
  - doctor_eval 6y ago
    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. [0] https://pubmed.ncbi.nlm.nih.gov/11706971/ https://pubmed.ncbi.nlm.nih.gov/11706971/
    - nnmg 6y ago
      > 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 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.
nottorp 6y ago
Please edit the title to fully spell out Multiple Sclerosis. At first I thought what does Microsoft have to do with nerve coatings?
- mettamage 6y ago
  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.
  - nottorp 6y ago
    Just to nitpick, if you're not a native english speaker MS may not even mean multiple sclerosis to you. In my language the acronym would be "SM". Later edit: and I've never seen the name of the disease acronymed, it's always been in full.
    - mettamage 6y ago
      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-sclerose-ms/ 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:)
    - ginko 6y ago
      Well, in my native language SM is something _very_ different. :)
    - 6y ago
irjustin 6y ago
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.
- derefr 6y ago
  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.
  - roganartu 6y ago
    > 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. [0]: https://en.wikipedia.org/wiki/Natalizumab https://en.wikipedia.org/wiki/Natalizumab [1]: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3128336/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3128336/
secondo 6y ago
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. [1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5474703/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5474703/ [2] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5109942/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5109942/
- melling 6y ago
  “Just 20 years ago..." 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.
  - aplummer 6y ago
    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.
    - melling 6y ago
      So, that wouldn’t be a good way to address basic medical research for some sort of Manhattan project. To make great progress over a decade, we’d need to do something else to advance medical science.
wrkronmiller 6y ago
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? [1] https://www.webmd.com/drugs/2/drug-17979/targretin-oral/details https://www.webmd.com/drugs/2/drug-17979/targretin-oral/deta...
- neltnerb 6y ago
  Could also be that the MS treatment effects are a different delivery mechanism.
- Ovah 6y ago
  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.
  - caymanjim 6y ago
    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.
- PragmaticPulp 6y ago
  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.
loceng 6y ago
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. Documentary on Emcell on YouTube: https://youtu.be/gYRcmDySFyE https://youtu.be/gYRcmDySFyE 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.
- cpncrunch 6y ago
  Its a scam. There is no evidence for any of this. Why are you shilling it here?
  - loceng 6y ago
    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.
    - cpncrunch 6y ago
      There is no research showing that stem cells are effective for these conditions. That's why it's a scam.
      - loceng 6y ago
        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.
JPLeRouzic 6y ago
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.
- JPLeRouzic 6y ago
  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: https://pubmed.ncbi.nlm.nih.gov/32916173/ https://pubmed.ncbi.nlm.nih.gov/32916173/
gavinray 6y ago
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.
- steelframe 6y ago
  Fascinating. I went through an Accutane treatment regimen as a teenager and went on to develop MS within a few years of finishing the treatment.
  - faeyanpiraat 6y ago
    With a big enough sample size, we could find someone who developed MS a few years after she stopped eating Broccoli. It wouldn’t mean it caused it though..
chime 6y ago
> 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.
- baldfat 6y ago
  My niece has aggressive MS and Ocrevus didn't help. CRSPR is the true dream. No more MS.
PragmaticPulp 6y ago
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/ 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/ 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.
GordonS 6y ago
> 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.
- revel 6y ago
  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.
  - GordonS 6y ago
    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.
- PragmaticPulp 6y ago
  > 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 https://www.karger.com/Article/Fulltext/498858#scrollNav-3-6 Otherwise, IVIG for SFPN is quite expensive just about anywhere.
Treblemaker 6y ago
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". Also: https://en.wikipedia.org/wiki/Flowers_for_Algernon#Synopsis https://en.wikipedia.org/wiki/Flowers_for_Algernon#Synopsis
nsxwolf 6y ago
I noted the use of the word "halt" in the article but not "reverse". Is it thought that remyelination would not reverse the effects of the disease?
rikelmens 6y ago
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. Edit: Just found another completed study [3] [1] https://pubmed.ncbi.nlm.nih.gov/29454153/ https://pubmed.ncbi.nlm.nih.gov/29454153/ [2] https://clinicaltrials.gov/ct2/show/NCT03995810 https://clinicaltrials.gov/ct2/show/NCT03995810 [3] https://www.jns-journal.com/article/S0022-510X(19)32236-1/fulltext https://www.jns-journal.com/article/S0022-510X(19)32236-1/fu...
- LinuxBender 6y ago
  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.
sjc01234 6y ago
wow. it is so cool to see this on HN! :O 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!!!
watersb 6y ago
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.
bradknowles 6y ago
They’re treating Microsoft addiction?!? Cool! ;) 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.

491 points by pujjad 6y ago

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.

thowaway1001 6y ago
It mat not be only the safety profile, but also the fact that drug patent has expired in 2016. I am sure they’ll come up with an alternative that may have similar or better safety profile and could pay for clinical trials. No company is going to finance Phase 3 trial on patent free drug.
- justinclift 6y ago
  Are you meaning the expiry of the 1999/2000 patents? There seem to be several others, including some filed recently: https://www.drugpatentwatch.com/p/generic-api/BEXAROTENE https://www.drugpatentwatch.com/p/generic-api/BEXAROTENE On a side note, is anyone aware of better info source that "drugpatentwatch.com"? That site seems to lock useful info behind a paywall.
james_pm 6y ago
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.
hardlianotion 6y ago
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.
- neltnerb 6y ago
  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.
  - Broken_Hippo 6y ago
    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.
    - neltnerb 6y ago
kzrdude 6y ago
How the disease hits is widely different and this generalization is incorrect - it might get some sufferers correct, but far from all. Source: friends with very normal lives
djsumdog 6y ago
> 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.
- Fnoord 6y ago
  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.
PragmaticPulp 6y ago
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.
deleted 6y ago
[deleted]

hprotagonist 6y ago

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. Translation: come back in 2040.

TheAdamAndChe 6y ago
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.
- epmaybe 6y ago
  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)
  - whymauri 6y 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.
- gavinray 6y ago
  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.
  - TheAdamAndChe 6y ago

vwat 6y ago

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.

shakna 6y ago
> 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.
- doctor_eval 6y ago
  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. [0] https://pubmed.ncbi.nlm.nih.gov/11706971/ https://pubmed.ncbi.nlm.nih.gov/11706971/
  - nnmg 6y ago
    > 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 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.

nottorp 6y ago

Please edit the title to fully spell out Multiple Sclerosis. At first I thought what does Microsoft have to do with nerve coatings?

mettamage 6y ago
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.
- nottorp 6y ago
  Just to nitpick, if you're not a native english speaker MS may not even mean multiple sclerosis to you. In my language the acronym would be "SM". Later edit: and I've never seen the name of the disease acronymed, it's always been in full.
  - mettamage 6y ago
    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-sclerose-ms/ 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:)
  - ginko 6y ago
    Well, in my native language SM is something _very_ different. :)
  - 6y ago

irjustin 6y ago

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.

derefr 6y ago
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.
- roganartu 6y ago
  > 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. [0]: https://en.wikipedia.org/wiki/Natalizumab https://en.wikipedia.org/wiki/Natalizumab [1]: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3128336/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3128336/

secondo 6y ago

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. [1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5474703/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5474703/ [2] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5109942/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5109942/

melling 6y ago
“Just 20 years ago..." 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.
- aplummer 6y ago
  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.
  - melling 6y ago
    So, that wouldn’t be a good way to address basic medical research for some sort of Manhattan project. To make great progress over a decade, we’d need to do something else to advance medical science.

wrkronmiller 6y ago

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? [1] https://www.webmd.com/drugs/2/drug-17979/targretin-oral/details https://www.webmd.com/drugs/2/drug-17979/targretin-oral/deta...

neltnerb 6y ago
Could also be that the MS treatment effects are a different delivery mechanism.
Ovah 6y ago
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.
- caymanjim 6y ago
  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.
PragmaticPulp 6y ago
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.

loceng 6y ago

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. Documentary on Emcell on YouTube: https://youtu.be/gYRcmDySFyE https://youtu.be/gYRcmDySFyE 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.

cpncrunch 6y ago
Its a scam. There is no evidence for any of this. Why are you shilling it here?
- loceng 6y ago
  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.
  - cpncrunch 6y ago
    There is no research showing that stem cells are effective for these conditions. That's why it's a scam.
    - loceng 6y ago
      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.

JPLeRouzic 6y ago

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.

JPLeRouzic 6y ago
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: https://pubmed.ncbi.nlm.nih.gov/32916173/ https://pubmed.ncbi.nlm.nih.gov/32916173/

gavinray 6y ago

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.

steelframe 6y ago
Fascinating. I went through an Accutane treatment regimen as a teenager and went on to develop MS within a few years of finishing the treatment.
- faeyanpiraat 6y ago
  With a big enough sample size, we could find someone who developed MS a few years after she stopped eating Broccoli. It wouldn’t mean it caused it though..

chime 6y ago

> 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.

baldfat 6y ago
My niece has aggressive MS and Ocrevus didn't help. CRSPR is the true dream. No more MS.

PragmaticPulp 6y ago

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/ 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/ 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.

GordonS 6y ago

> 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.

revel 6y ago
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.
- GordonS 6y ago
  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.
PragmaticPulp 6y ago
> 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 https://www.karger.com/Article/Fulltext/498858#scrollNav-3-6 Otherwise, IVIG for SFPN is quite expensive just about anywhere.

Treblemaker 6y ago

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". Also: https://en.wikipedia.org/wiki/Flowers_for_Algernon#Synopsis https://en.wikipedia.org/wiki/Flowers_for_Algernon#Synopsis

nsxwolf 6y ago

I noted the use of the word "halt" in the article but not "reverse". Is it thought that remyelination would not reverse the effects of the disease?

rikelmens 6y ago

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. Edit: Just found another completed study [3] [1] https://pubmed.ncbi.nlm.nih.gov/29454153/ https://pubmed.ncbi.nlm.nih.gov/29454153/ [2] https://clinicaltrials.gov/ct2/show/NCT03995810 https://clinicaltrials.gov/ct2/show/NCT03995810 [3] https://www.jns-journal.com/article/S0022-510X(19)32236-1/fulltext https://www.jns-journal.com/article/S0022-510X(19)32236-1/fu...

LinuxBender 6y ago
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.

sjc01234 6y ago

wow. it is so cool to see this on HN! :O 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!!!

watersb 6y ago

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.

bradknowles 6y ago

They’re treating Microsoft addiction?!? Cool! ;) 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.