BioNTech CEO applies Covid-19 vaccine's mRNA tech to multiple sclerosis

Please provide a link to your thesis.

Don't feel too bad, the execution depended on a massive world-changing pandemic where funding flowed freely and normal economics just didn't apply.

Not to worry! When I was a little kid, I couldn't afford new shiny magazines,so I had an idea of an online library hosting all the magazines for a small monthly fee. Guess what, turns out apps like Readly doing exactly that.

We don’t even know if this will work so I wouldn’t feel too bad.

I read somewhere recently that CRISPR was actually causing far more accidental mutations than anticipated. Apologies I do not have the source handy, though Google should turn up some information.

CRISPR is a great example of a technology that has not yet made a meaningful economic contribution. Although the technique for editing DNA was discovered in 2012—and a Nobel Prize was awarded to its two discoverers this year—no treatment using CRISPR has been approved outside of clinical trials. So far, its impact has been limited to making researchers more productive—not a bad thing, to be sure, but not close to CRISPR’s full potential. As trials progress, however, I do think some CRISPR treatments will come online in the next few years, especially those targeting genetic disorders that we have very limited means of otherwise treating.

From Notes on Technology in the 2020s - Eli Dourado

The vaccine (or vaccine product, not sure which) targets the cells that modulate the immune response.

If I understand correctly, it gets the cells to produce the same autoantigen that they are misidentifying, which causes them to slow that activity.

It reads like the immune isn't forgetting anything, they just "flood" the system with the proteins that the antibodies would normally attack in nerve cells or brain, thus giving the antibodies another target to "keep them busy".

It sounds like they are creating large quantities of the "offending" protein via the vaccine mNRA mechanism in normal cells. Normally the antibodies/T-cells would attack the myelin coating of nerves and the brain but with the protein being abundantly available anywhere the immune cells are "kept occupied" and leave nerves and brain alone.

If this treatment works as I understand, you would need continuous refreshers each time the mRNA injection is depleted.

In a sense it sounds a bit like immunotherapy for allergies. That is typically about injecting pathogens into your body (e.g. under your tongue, under your skin, or in your lymph nodes), and then over time teaching your body that these pathogens are harmless.

As far as _why_ that works instead of sending someone into anaphylactic shock... ¯\_(ツ)_/¯ The immune system is weird and complex, and I guess that's why they want a medical specialist around in case you're one of the unlucky ones. (Only the first time with sublingual tablets as far as I know)

Derek Lowe, as usual, explains this quite nicely: https://blogs.sciencemag.org/pipeline/archives/2021/01/12/mo...

To quote:

One goal has been to try to selectively affect autoreactive T cells, but that’s a lot easier said than done. The regulatory T cells and regulatory B cells are key players in immune tolerance, the “friend or foe” recognition system that keeps our own immune systems from attacking everything in sight. If you could present some of the antigens involved to those cells in a way that they accepted them as normal human proteins rather than as an external threat, you could presumably turn down their response.

BioNTech and others have been trying to target the population of lymphoid antigen-presenting cells, known to be very important in immune tolerance mechanisms, but without setting off any of the general inflammation pathways. They have a liposomal formulation that when injected into the muscle tissue seems to end up almost entirely in the lymphatic system, and they’ve been doing all sorts of modifications to the RNA payload (such as replacement of uridine with methylpseudouridine) to make it as non-immunogenic by itself as possible. The liposome lipids themselves are also chosen to be as non-immunogenic as possible, too – the coronavirus mRNA vaccines actually get an adjuvant boost from such properties, but you don’t want that in this case.

Guys, correct me if I'm wrong... NickM, you can understand mRNA in this case as a software/firmware update for an operating system to fix bugs. So you can basically teach the body that he is doing something wrong (e.g. autoimmune disease) and tada the body is not doing it anymore

According to my wife, who is an immunologist working on this same mRNA tech, but applied to cancer, it also has promise in treating allergies -- both the food kind and the kind I have (animals).

As I've understood, (correct me if I'm wrong) one of the main concerns is that you end up with a protein that interferes with other functions of the body in unexpected ways. So I guess it would be prudent to go through phase 1-3 trials again.

Yes, they will have to go through health and safety trials for each additional vaccine developed using this technology. No one gets special treatment when it comes to FDA approval, and this is the way it should be.

You can get fast tracked if you show superior effectiveness, meet an unmet medical need, or get rid of serious side effects of an existing therapy. We should look at ways to speed up this process, (in the grand scheme of things 9 months isn't that long to wait to cure a disease) not eliminate it altogether. If we approved something that actually does harm, it will further undermine efforts to widely vaccinate the public. We already have issues with people trusting vaccines when there is no evidence of negative effects, I can't imagine how hard it would be if we had another thalidomide on our hands.

Of course they will. The issue is with the things the mRNA codes for, and not with the mRNA.

Yes. BioNTech are already into phase 1s and phase 2s with several others. My wife works on one of the programs targeting cancer, which has years of development and trials behind it.

Pretty screwed for at least another year.

Using a vaccine created by one of the many other mechanisms that are in the pipeline, like the Oxford or J&J vaccines.

https://www.nytimes.com/interactive/2020/science/coronavirus...

We’d be much happier with Astra-Zeneca.

I'd assume the traditional route of using virus particles for the vaccine would be used. In fact, I think that's what the Chinese and Russians are using.

If this hit 20 years ago I suspect that we wouldn't have perceived anything but the tip of the iceberg of people who actually die or get close, because PCR was much less industrialized back then. And the big invisible "underwater part" of young or lucky people who don't get bad Covid but still serve the virus as transmitter relays would have made it a very strong, short wave. Likely mass graves in every part of the world, but mostly over I think by late summer 2020.

And so much individual suffering, because Covid deaths seem to be pretty far from peacefully dozing off. On this scale, which is orthogonal to all the usual metrics, I believe that it's considerably worse than 1918. If this virus had hit us before we got the tools for asymptomatic detection it would have likely lead to quite a few changes in our approach to end of life care, instead of the extra progress we now see in our utilization of the mRNA toolbox.

Casually backwards but the audience can relate better this way.

Well, Covid is what made the technologies breach the apply to humans threshold. Could have taken ages otherwise, because the testing procedures create quite a bit of conservative bias (and I don't blame them)

Given that it doesn't suppress the immune system as much as existing treatments, other parties will likely tell them to go away (patients, doctors, insurance, etc.).

Wouldn't insurance companies love a lower cost one time treatment?

Avonex is off patent - still profitable, but drug companies are not entirely insensitive to being displaced by breakthroughs.

Where does it say it'd be only $20 ?