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.<p>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.<p>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.<p>[1] <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5474703/" rel="nofollow">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5474703/</a><p>[2] <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5109942/" rel="nofollow">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5109942/</a>
While it is sad that this drug cannot continue for MS directly, I love that this is science work at its best.<p>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.<p>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.
> 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<p>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 <i>very</i> expensive treatment, and the NHS will not pay for it).<p>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.
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.<p>Translation: come back in 2040.
> 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.<p>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.<p>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.<p>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.<p>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’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.<p>I fully believe that for chronic life threatening diseases people should be allowed to try all sorts of treatments that would be deemed unsafe.
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.<p>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: <a href="https://pubmed.ncbi.nlm.nih.gov/30903705/" rel="nofollow">https://pubmed.ncbi.nlm.nih.gov/30903705/</a><p>Likewise, the effects on blood lipids are significant enough that patients are frequently forced to take statins during their course of treatment: <a href="https://pubmed.ncbi.nlm.nih.gov/29805374/" rel="nofollow">https://pubmed.ncbi.nlm.nih.gov/29805374/</a><p>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.<p>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.<p>The structure is very close to another popular drug, Isotretinoin (Accutane), with similar side effects.<p>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".<p>Also:
<a href="https://en.wikipedia.org/wiki/Flowers_for_Algernon#Synopsis" rel="nofollow">https://en.wikipedia.org/wiki/Flowers_for_Algernon#Synopsis</a>
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]<p>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.<p>Unofficially, I've heard it was a great success. But let's wait.<p>Edit: Just found another completed study [3]<p>[1] <a href="https://pubmed.ncbi.nlm.nih.gov/29454153/" rel="nofollow">https://pubmed.ncbi.nlm.nih.gov/29454153/</a>
[2] <a href="https://clinicaltrials.gov/ct2/show/NCT03995810" rel="nofollow">https://clinicaltrials.gov/ct2/show/NCT03995810</a>
[3] <a href="https://www.jns-journal.com/article/S0022-510X(19)32236-1/fulltext" rel="nofollow">https://www.jns-journal.com/article/S0022-510X(19)32236-1/fu...</a>
wow. it is so cool to see this on HN! :O<p>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.<p>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.<p>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.<p>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.<p>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.
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?
They’re treating Microsoft addiction?!? Cool! ;)<p>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.<p>Is it that the dosages must be higher to treat MS?<p>[1] <a href="https://www.webmd.com/drugs/2/drug-17979/targretin-oral/details" rel="nofollow">https://www.webmd.com/drugs/2/drug-17979/targretin-oral/deta...</a>
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.<p>Documentary on Emcell on YouTube: <a href="https://youtu.be/gYRcmDySFyE" rel="nofollow">https://youtu.be/gYRcmDySFyE</a><p>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.
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.