I came up with the same idea for treating autoimmune disease years ago - in my first year of med school, actually. Back then the platform for doing this elegantly via mRNA didn't really exist, though, and I didn't want to drop out of med school to spend a half-decade or more in grad school proving the concept the clumsy way.
I'm really glad that it's finally come to fruition, but I definitely feel a bit of regret that I have come to embody the "ideas are cheap, execution matters" truism.
They were working on applying mRNA technology to other diseases, including (and in particular) cancer, well before the pandemic. While it is true that they have received significant funding this year, they had a $7.6B market cap on Dec 31, 2019 and were already conducting several clinical studies for mRNA-based medicine [1].
IMO, the healthier coping mechanism is to realize that the path you take in life will never be the most optimal. We all make mistakes, and if all we care about is extrinsic achievement, we'll be either steeped in regret (or perhaps, blissfully ignorant). Instead of being outcome dependent, try to value things that are by nature, intrinsic.
No. The cash helped develop a vaccine this fast, but further application comes with the recent innovation in the lipid nano particles for delivery. That was done before the pandemic.
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.
I really hope this mRNA train keeps going and companies succeed executing on it. Does anyone know the status for CRISPR medical technology? I remembering hearing about all these great applications using CaaS-9 and 13 but I haven’t really heard any new medical breakthroughs recently (though the hemophilia “cure” was awesome!).
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
CRISPR most definitely made a huge economic contribution. It's used massively
https://pubmed.ncbi.nlm.nih.gov/?term=crispr
and it allows to do things that would have been very difficult (and expensive, thus providing value) to do otherwise, allowing researchers to do new therapies and diagnostic tools that WERE applied in clinic.
That's a bit like saying containers haven't provided meaningful economic contribution because consumers don't use them very often.
I state that CRISPR benefits researchers. However, that is still a niche benefit relative to the long term societal benefits we anticipate from CRISPR.
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.
Oh man, this is amazing news. I am surprised at how much promise mRNA has! Let’s hope it will not be too long before awful conditions like MS are consigned to history.
I've re-read the article a couple of times but I'm having trouble understanding how this works. I understand how an mRNA vaccine can teach the immune system to recognize a virus, but in the case of an autoimmune disorder, the challenge is to teach the immune system to stop attacking something, right?
How can an mRNA vaccine cause the immune system to "forget" something that it thinks is harmful?
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)
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.
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.
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).
I haven't yet seen anyone mention this, but will BioNTech's / Modernas mRNA vaccine need to go through phase 1-3 trials when encoding for other proteins?
The greatest advancement with mRNA is that you can have a vaccine in under a month. But that doesn't help if for each new mRNA encoding you need 9 months worth of health & safety trials.
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.
> 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.
true, but there are loopholes. the 510(k) loophole for medical devices where any device that is "substantially equivalent" to an existing approved device can get fast track approval has proved problematic. this has been publicly documented both in the press and in independent documentaries for some time.
The have to go through an approval process on every update but AFAICR only with a study including 300 adults, so substantially less then the tens of thousands that were included in the Biontec/Moderna trails.
Thanks. So they only test for lack of side effects, not for effectivity (outside of leech dish experiments), because with just 300 it would take decades to see a meaningful delta? (unless they do challenge tests?)
That's talking about selection for production, not about development. How is development not part of three scope at all? Are they only selecting amongst a pre-developed library? Do they have a reusable process that goes from strain to vaccine and "just works"? The latter would be very similar to a liberal approach like "we got delivery mechanism for mRNA blueprint of spike protein X approved, we can use the same approval for spike protein Y".
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. 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.
When I first read of the messenger RNA based vaccines I was thinking that perhaps the one good thing coming from this horrific pandemic is providing mRNA treatments the funding they needed.
I think originally BioNTech worked on cancer treatments.
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.
>I believe that it's considerably worse than 1918.
The COVID IFR is known to be lower than that of the 1918 influenza pandemic, which killed between 50 and 100 million people in less than a year, and pulled that off at a time when the Earth's population was a quarter of what it is today and much less mobile. I have no idea whatsoever where you get the idea that COVID is worse than 1918. It most emphatically (at least so far) is not at all showing itself to be as bad, let alone worse.
If it was describing that as "worse", didn't leave it very clear, and in any case, that's an awfully ambiguous comparison. Death from influenza was slowly asphyxiating, and sometimes even hemorrhagic, neither of which sound especially peaceful.
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.
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)
Great news! I wonder how much industry resistance there will be. Treating MS patients is a massive industry. Drug treatments are $100k a year currently, replacing that with a single $20 vaccine would be disruptive in the best way.
Doubtful. Insurances dont run at a loss, every penny that goes into them they take a cut as profits. If the treatment is expensive, great! More demand for their product, and even if their cut is the same, their profit and revenue will be greater.
There's an 80/20 rule in the ACA [0] where at least 80 percent of the premiums paid must be spent on healthcare costs, otherwise the difference between 80 percent and the actual amount paid must be returned.
Sounds great, until the insurance companies figured out that the best way to make more profit with this profit cap is to pay out more and increase the premiums accordingly. [1] Obviously, the hospitals don't mind that either.
I'm sure they would, but bear in mind that the costs are likely going to be much higher for an MS vaccine than for nCov2, due to the economies of scale that the latter has. Insurance companies will still probably love a one-time $20,000 (or whatever number they can justify) treatment compared to ongoing costs.
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.).
Indeed. It most certainly won’t be $20. If it permanently “cured” someone of MS they could charge hundreds of thousands and insurance companies would gladly pay it.
Big Pharma is likely very pro covid vaccine boon, 1) because some got a free loan to fund improvements of their own MRNA tech to catch up to Moderna's 10 year head start and 2) as an excuse to now field their MRNA tech with new vaccines and therapies when in prior years there would have been insurmountable barriers due to the FDA and lack of existing pharmacological precedent.
I'm really glad that it's finally come to fruition, but I definitely feel a bit of regret that I have come to embody the "ideas are cheap, execution matters" truism.