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A noninflammatory mRNA vaccine for treatment of autoimmune encephalomyelitis (science.sciencemag.org)
88 points by lawrenceyan 9 days ago | hide | past | favorite | 29 comments

So excited by this ! Im 30 and finally, after reading tons of papers about AS and/or inflammatory pathways it is the first time I can imagine a cure for my anlylosing spondylitis. Too bad it will take years of approval once developed. I volunteer for trials and not in the placebo group please !

I can't see the full text of the article and most of the abstract is over my head. Is AS mentioned in the paper or are you just hopeful that a similar thing could be developed for AS and other autoinflammitory diseases?

The same method very likely could work for most auto-immune conditions if they can repeat the basic method in humans. They’re essentially turning on and/or ramping up the existing self-regulation mechanism of the immune system. I’ve only read the abstract, but what I’m not sure about is their selective delivery/targeting method, as that seems the hardest part. The various regulatory pathways cells are fairly well studied for most AI conditions and the mRNA sequences for their associated receptors could be programmed readily as I understand the technology.

However, if it does work in humans it’ll be a huge leap forward for treatment of auto immune diseases. Perhaps long term, even inflammatory issues like arterial plaque, which we’re slowly realizing is formed by chronic inflammation as much as by high cholesterol. Alzheimer’s May also be largely driven by incorrect immune responses too.

I suspect the challenge will be long term mRNA suitability, e.g. if the mRNA delivery mechanisms will develop immune reactions of their own. The cost of delivering the mRNA treatments could be large too. Biologics for autoimmune conditions require self administered shots too, but don’t require deep freezer cold. Also it could increase long term cancer risks by over stimulating self-regulatory pathways.

Not sure if the full article mentions if it’s a one time shot or on going. I’m presuming ongoing dice mRNA will degrade.

Another complication with RA and AS will be the number of linked autoantigens involved. Both RA and AS likely will benefit from collagen II autoantigens but also appear to be triggered by a bunch of other autoantigens as well. Still mRNA should cope with that case better than current methods too! It’s easy to print lots of different antigens in one go.

See https://pubmed.ncbi.nlm.nih.gov/12678429/

Were it to work in humans, does anyone know if there is any reason such an approach couldn't be extended to other autoimmune disorders which attack the various other tissues of the body?

I think this is what they are eventually aiming for. Half of the authors is affiliated with BioNTech of BioNTech/Pfizer-mRNA-vaccine-fame by the way.

When people think vaccine they think, ‘only effective if taken beforehand’. Is that the case for mRNA vaccines?

I don't think that's ever the case actually. It's just that the immunity conveyed by an active infection often is as good or better than what a vaccine would produce so there's no reason to apply the vaccine after an initial immune response. But just like some vaccines, after an infection you may need a booster later to maintain immunity.

Though for this specific vaccine the question is somewhat irrelevant. In this case, they are introducing an antigen that the underlying condition, MS would never cause to occur. This antigen activates regulatory cells which then supress the immune systems production of myelin targeting antibodies.

So in the case eof a normal vaccine, regardless of whether it is mRNA or not, the vaccine is conveying information to the immune system that you might also acquire through an active infection.

This vaccine however is conveying information to your immune system that no active infection would convey.

This all kind of answers my own question which would seem to be yes. As long as they can find an autoantigen that will stimulate regulatory cells which supress the problematic autoantibody producing immune cells. At least that is my read after mucking through the medical jargon.

Vaccine implies acquired immunity. Exactly same mRNA tech can potentially be used to treat cancer, cardiovascular or metabolic diseases, only the messenger RNA changes. It's probably called mRNA drug instead of mRNA vaccine even if the process is the same.

mRNA is tech that BioNTech is developing is completely digital. Once you have the RNA structure in the computer, you can just "print out" drug/vaccine using the same process without changing anything else.

i seem to recal that with this technology personalized anti-cancer drugs thst teach the immune system can be created with low cost at some point... seems like a real revolution if true...

Some vaccines are effective after exposure. The rabies vaccine for example is commonly given to people after exposure. As long as it is given soon, it can save your life.

I could be wrong but I'm not sure the rabbies vaccine is a good example. Because even though it is effective after rabbies enters the body I'm not sure it is effective after the initial immune response which may only occur once the virus reaches the central nervous system. Not saying you're wrong, I just genuinely don't know if an immune response is triggered by the virus before that.

Going from memory here so I may be wrong, but rabies takes a while to travel along nerve pathways from the bite site to your brain, and that's why the vaccine has time to work.

If an auto immune disease damages your body but then it stops manifesting, your body will remain damaged. A medical treatment for the caused damage would be called a cure in this case. Vaccines that stop the auto immune response are not cures. A somewhat helpful example is pancreas transplant for type 1 diabetics: the person with the transplant would be "cured" (ie they'd have their own insulin production) but the auto immune disease will destroy the donor pancreas eventually. Hopefully in the future we will have complete, synergistic treatments that take care of both.

Wouldn't this depend on the type and severity of the autoimmune disorder? Someone with mild Rheumatoid Arthritis for example would be effectively cured if the inflammatory antibodies were supressed as their inflamed joints would largely be able to heal near to their original state.

You are completely right, in many autoimmune disorders if the damage is stopped in time it could be cured.

Some autoimmune diseases cause damage that can be healed though.

that's why i've been saying that the mRNA vaccine delivery method could be the next paradigm shift... like antibiotics were.

I think that this could be thought as part of a more general revolution: the know-how to program the immune system. This would include things like T-Cells therapy for cancer (1)

(1) - https://science.sciencemag.org/content/371/6525/145

I don't know why you're being down voted. mRNA and tcell programming is the future of medicine. We may literally not have to worry about pathogen borne, auto immune, or cancer ever again...

Please check my understanding:

Some cells in the body present features that teach the immune system that these features are 'OK' and part of the healthy body and shouldn't be attacked.

This therapy seeks to cause those cells to produce features, or produce more of some features, that are being incorrectly recognized as 'bad' by the immune system. Thus correcting the immune systems 'understanding' and suppressing mistaken attacks on the body which underlies auto-immune disorders.

Comparing notes, my understanding is that it causes the production of additional structures which supress the specific parts of the immune system which are attacking the body.

Wow so we could make rna to produce pollen and treat seasonal allergies?

The benefice/risk would not be worth it for such benign allergies

Those are not necessarily benign allergies. They can trigger asthma attacks which can be life threatening in some cases.

I’m hearing the risk is very minimal though.

Cost/benefit at least, compared to respiratory protection and decontamination.

I have vitiligo, I wonder if this could help me?

Please explain like I'm five.

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