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

theguardian.com

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

#21

Post by epmaybe »

TheAdamAndChe wrote: post #16
hprotagonist wrote: post #3

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.

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)

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

#22

Post by shakna »

unionpivo wrote: post #17
shakna wrote: post #9

Earlier quoted context omitted.

> 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.

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.

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

#24

Post by darkerside »

doctor_eval wrote: post #15
shakna wrote: post #9

Earlier quoted context omitted.

> 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…

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?

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

#25

Post by H_Pylori »

doctor_eval wrote: post #15
shakna wrote: post #9

Earlier quoted context omitted.

> 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…

A couple of interesting articles that may be related to what you are saying.

https://pubmed.ncbi.nlm.nih.gov/22189514/

https://pubmed.ncbi.nlm.nih.gov/20676785/

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

#26

Post by furyg3 »

nottorp wrote: post #8

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

I like that you got all the way to nerve coatings before you were confused. "MS treatment a step closer after drug shown to..." was all fine :)

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

#27

Post by kinow »

nottorp wrote: post #13
mettamage wrote: post #12

Earlier quoted context omitted.

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 pow…

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.

Good point, had no idea what was MS until I read the comments. In my language it's "esclerose múltipla", and have never seen it acronymed.

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

#28

Post by whymauri »

epmaybe wrote: post #21
TheAdamAndChe wrote: post #16

Earlier quoted context omitted.

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.

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

#29

Post by nnmg »

doctor_eval wrote: post #15
shakna wrote: post #9

Earlier quoted context omitted.

> 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…

> 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.

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

#30

Post by secondo »

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/

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

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