So the long term risks are mostly from secondary infection, and it's only half of the 5-11% of the cases of mortality after treatment.
I think that sounds pretty fucking good considering the other option is definitely just being dead. That's as close to a miracle treatment as I believe we will get.
For the sake of my question let’s assume this is legit and magically works for a wide range of autoimmune conditions. How many years away are we from being able to sign up for this treatment? 10 years? 20? 30?
It would be nice to dream of it happening sometime soon.
Only for orphan and ultra orphan diseases where there are so few patients that it’s not economically viable to do full clinical trials.
There is also a breakthrough therapy designation where the clinical evidence is solid enough to release the drug while they finish full trials but that’s only in exceptional cases.
Not really, the process gets shortcut when the benefits of moving fast are dramatic enough.
So sure we could speed things up by killing more people undergoing medical experiments. But the current approach of validating safety in humans then efficacy in humans is inherently serial. Further a lot more stuff is going into the pipeline than actually ends up working.
amen. I've tried 3 tnf inhibitors that have not worked (and had negative side effects). Cosentyx (il 17a inhibitor) kinda scares me. I always like to keep my hopes that some better autoimmune treatments could come soon
For context, I had been on Taltz before for psoriasis, and it worked very well. It seems like il17 inhibitors specifically are extremely targeted in what they affect.
In comparison, I was also on otezla at one point (tnf-a inhibitor) and it didnt work for me either, and the side effects were terrible.
(Please don’t downvote me because you don’t like the tone of that. Europe banned artificial food colors and Japan is using self-replicating RNA vaccines. There is a wide spectrum of risk tolerance and healthcare does not revolve around the USA)
I'm not sure about Mexico, but here in Argentina I think we wait until the drug gets a the FDA or EMA approval and ask for a copy, well we probably ask for all the paperwork but I don't remember cases of weird fast local approvals. It's possible to buy Metamizole/Dipyrone here https://en.wikipedia.org/wiki/Metamizole . Anyway, we have special cases, like a vaccine for a local illness https://es.wikipedia.org/wiki/Virus_Jun%C3%ADn that I guess is not approved anywhere else.
Every few years, there is an scandal for illegal medicine, but I think most of the case it's about using industrial silicone in human cosmetic surgery or something as stupid like that, not cutting edge new drugs. Perhaps it's possible to get tourist-illegal-medicine, but I strongly advice against that.
---
> Japan is using self-replicating RNA vaccines
Do you have a source for that? I can try to take a look. I suspect it's very bad journalism reporting.
Self-replicating RNA are just https://en.wikipedia.org/wiki/Viroid but they only survive in plants, not animals. If they make their own coating, they are retrovirus. Writing a retrovirus from scratch is too difficult, some vaccines use edited virus, where they add the interesting part but also remove another part to the virus can't reproduce outside the lab. And there are vaccines with "live" attenuated virus, like the oral polio vaccine, but they are more difficult to make.
Thanks. Very interesting. From the research paper:
> The ARCT-154 study vaccine consists of sa-mRNA encapsulated in lipid nanoparticles. The RNA comprises a replicon based upon Venezuela equine encephalitis virus (VEEV) in which RNA coding for the VEEV structural proteins has been replaced with RNA coding for the full-length spike (S) glycoprotein of the SARS-CoV-2 D614G variant.
IIUC the RNA makes copies of itself inside the cell, but it does not get a capsule of proteins to travel and invade other cells. Is this correct?
All of these amazing therapies coming out of applied biology are based on years and years of basic science that has been done in universities across the world. Much of it funded by the US NIH. Unfortunately funding for basic science is very hard to come by.
Imagine if the billions of dollars being blown on boiling the oceans for a slightly better autocorrect were being used on basic and applied biological research instead. I have no doubt many afflictions would be a thing of the past (at least for those who embrace science instead of superstition).
> In FY2024, NIH received a total program level of $47.311 billion, a decrease in its overall program level (-$368 million, or -0.8%) for the first time since FY2013.
The NIH already gets $47 billion per year, do you think they should get more?
That sounded almost too good to be true, especially with autoimmune stuff which seems even trickier to tackle than many cancers. One hell of achievement if it pans out long term.
I suffer from psoriasis.
This seems like another 'solution' that really only addresses how the diseases manifest but not the root cause.
I can go get a shot today that blunts my immune system, and my psoriasis will calm down for a year but I'll probably get a couple wicked chest colds.
Autoimmune diseases in no small part ruined my life. Forgive me if I seem rude, but I don't trust pharma to solve jack or shit without the correct financial incentives, and those proper financial incentives just can't organically exist for chronic sufferers of any novel disease.
> This seems like another 'solution' that really only addresses how the diseases manifest but not the root cause.
If you read the article, you'd see that one of the features is that in the vast majority of cases, the B-cells return, but not the B-cells that were causing the immunodeficiency
quote: "Once injected into the hosts, the CAR T cells got to work. They multiplied and targeted and destroyed all the B cells — including pathogenic cells linked to the autoimmune conditions. The bioengineered T cells survived for weeks in the recipients before largely vanishing. Eventually, new healthy B cells returned, but no pathogenic ones did. A similar response has been observed in people with autoimmune conditions who received CAR T cells derived from their own cells."
My point being that the immune system appears to remains functional with this treatment, differentiating it from the clinical therapies that are available to you currently.
Speaking as someone who has also been let down by the medical system, but also who wouldn't be alive without it: I agree that Big Pharma is a problem (anyone disagreeing with that is arguing against the scientific evidence -- Ben Goldacre's book Bad Pharma is a good introduction to the problems with the industry), and that in the gross case they are lacking financial incentives. At the same time, this does not mean that the clinical therapies we have or are developing, are utterly ineffective.
I thoroughly agree with your grayed comment. It doesn't necessarily imply that it's all greed and evil, but there's enough of it to dignify your statement, without applying my own experience.
There's nothing preventing pharma companies from just charging the equivalent of a lifetime supply for a one-off treatment. In fact, this is how cancer treatments are priced at the same time being the single largest source of revenue for pharma:
I'm not directly arguing against this, but it seems to me that this would eliminate a large part of the 'survival market'. Incremental debt, paycheck to paycheck accounts for much of the population.
Personally, I'd rather explore Elysium than give the entirety of my already insufficient and all prospective funds to what I consider pharmaceutical pimps. Poverty in America is, in my experience, worse than much of the 3rd world, where the practice is often more salubrious, less stigmatized and better performed, depending on one's values.
My friend would have long been dead of hep-c had he remained in the US. Although the US is my home and I'll go nowhere else, he took advantage of his Aussie ancestry and obtained citizenship, relocated and was treated for free. Here it would have been at least 250,000.
On the subject of cancer treatment, notably in the US, I'll not argue the subject, but will directly offer my perspective, which views it as highly exploitative and financially motivated. One example is the absurd reluctance to embrace or iin some cases, explore, the subject of enzymatic therapies and other 'foreign' procedures.
I'm an incorrigible cynic here and not worth trying to educate.
Does this new donor-cell therapy potentially include the top-10 autoimmune diseases, such as rheumatoid arthritis, lupus (checked), and/or Hashimoto's thyroiditis?
While the promise is great, let's be real. All of these personalised therapies get loads of funding because they almost inherently will be very expensive since they cannot scale, meaning drug manufactures supplying these can make a killing even compared to already expensive but more commonly used therapies. I guess this is more a comment on car-t usage in oncology and if this leads to seriously improved health outxomes, then of course, all the power to them.
This approach does scale, but has new safety risks.
They aren't genetically modifying each patient's own cells, one patient at a time, but are trying to create a line of generic T-cells that will attack only the B-cells of any patient.
The risk is that genetically modified T-cells that are not derived from your own cells might attack all the cells of your body, and not just your misbehaving B-cells.
They have made additional modifications to the CAR-T T-cells that they believe will prevent them from going rogue, but more safely testing is needed.
From what I've read, this same more generic approach is being attempted with CAR-T cancer treatment as well.
I understand this therapy is inherently more complex, but there are plenty of medical treatments that have helped millions of people without scaling like a drug: IVF, cognitive behavior therapy, casts for broken bones, etc.
Maybe I’m too optimistic but I’m sure the overall cost can be reduced dramatically over time even with individualization.
I'm not sure that I understand what you're saying.
These therapies are very individualized and will probably be very expensive.
How is CBT and casting a broken bone in any way like that? Those two things aren't reliant on medicine at all. Please explain, because I feel kind of stupid right now.
Derek Lowe on this use of CAR-T: https://www.science.org/content/blog-post/car-t-autoimmune-d...
And on the apparent long term risks of CAR-T: https://www.science.org/content/blog-post/downside-car-t-the...
So the long term risks are mostly from secondary infection, and it's only half of the 5-11% of the cases of mortality after treatment.
I think that sounds pretty fucking good considering the other option is definitely just being dead. That's as close to a miracle treatment as I believe we will get.
For the sake of my question let’s assume this is legit and magically works for a wide range of autoimmune conditions. How many years away are we from being able to sign up for this treatment? 10 years? 20? 30?
It would be nice to dream of it happening sometime soon.
Maybe not long at all. Scroll down to the section that says "Our Approach : Building a Designer Immune System" on this site[0]
[0]https://orcabio.com/what-we-do/
In the US, my "back of the napkin" estimate tends to be 8-15 years, if it passes trials.
Is there a way to speed up trials without compromising quality?
Only for orphan and ultra orphan diseases where there are so few patients that it’s not economically viable to do full clinical trials.
There is also a breakthrough therapy designation where the clinical evidence is solid enough to release the drug while they finish full trials but that’s only in exceptional cases.
Possible to use surrogate endpoints, which is used for slower evolving diseases. But then the claims need to be associated with the new endpoints.
FDA can fast track certain drugs, but it really needs to show amazing efficacy.
https://www.outsourcedpharma.com/doc/an-overview-of-the-fda-...
Not really, the process gets shortcut when the benefits of moving fast are dramatic enough.
So sure we could speed things up by killing more people undergoing medical experiments. But the current approach of validating safety in humans then efficacy in humans is inherently serial. Further a lot more stuff is going into the pipeline than actually ends up working.
amen. I've tried 3 tnf inhibitors that have not worked (and had negative side effects). Cosentyx (il 17a inhibitor) kinda scares me. I always like to keep my hopes that some better autoimmune treatments could come soon
Out of curiosity I'm curious why it scares you?
For context, I had been on Taltz before for psoriasis, and it worked very well. It seems like il17 inhibitors specifically are extremely targeted in what they affect.
In comparison, I was also on otezla at one point (tnf-a inhibitor) and it didnt work for me either, and the side effects were terrible.
Depends. Do you want to be a patient, or a trial test subject?
I would assume they primarily would like to suffer less.
My uncle has developed an autoimmune respiratory disease over twenty years ago, and I know he would give a whole lot to improve his condition.
In Mexico, maybe a year?
(Please don’t downvote me because you don’t like the tone of that. Europe banned artificial food colors and Japan is using self-replicating RNA vaccines. There is a wide spectrum of risk tolerance and healthcare does not revolve around the USA)
I'm not sure about Mexico, but here in Argentina I think we wait until the drug gets a the FDA or EMA approval and ask for a copy, well we probably ask for all the paperwork but I don't remember cases of weird fast local approvals. It's possible to buy Metamizole/Dipyrone here https://en.wikipedia.org/wiki/Metamizole . Anyway, we have special cases, like a vaccine for a local illness https://es.wikipedia.org/wiki/Virus_Jun%C3%ADn that I guess is not approved anywhere else.
Every few years, there is an scandal for illegal medicine, but I think most of the case it's about using industrial silicone in human cosmetic surgery or something as stupid like that, not cutting edge new drugs. Perhaps it's possible to get tourist-illegal-medicine, but I strongly advice against that.
---
> Japan is using self-replicating RNA vaccines
Do you have a source for that? I can try to take a look. I suspect it's very bad journalism reporting.
Self-replicating RNA are just https://en.wikipedia.org/wiki/Viroid but they only survive in plants, not animals. If they make their own coating, they are retrovirus. Writing a retrovirus from scratch is too difficult, some vaccines use edited virus, where they add the interesting part but also remove another part to the virus can't reproduce outside the lab. And there are vaccines with "live" attenuated virus, like the oral polio vaccine, but they are more difficult to make.
https://www.prnewswire.com/news-releases/japans-ministry-of-...
Your characterization is inaccurate, of both the reporting and the technology
Thanks. Very interesting. From the research paper:
> The ARCT-154 study vaccine consists of sa-mRNA encapsulated in lipid nanoparticles. The RNA comprises a replicon based upon Venezuela equine encephalitis virus (VEEV) in which RNA coding for the VEEV structural proteins has been replaced with RNA coding for the full-length spike (S) glycoprotein of the SARS-CoV-2 D614G variant.
IIUC the RNA makes copies of itself inside the cell, but it does not get a capsule of proteins to travel and invade other cells. Is this correct?
(A few more details in https://en.wikipedia.org/wiki/MRNA_vaccine#Amplification but not enough for my curiosity level.)
All of these amazing therapies coming out of applied biology are based on years and years of basic science that has been done in universities across the world. Much of it funded by the US NIH. Unfortunately funding for basic science is very hard to come by.
Imagine if the billions of dollars being blown on boiling the oceans for a slightly better autocorrect were being used on basic and applied biological research instead. I have no doubt many afflictions would be a thing of the past (at least for those who embrace science instead of superstition).
> In FY2024, NIH received a total program level of $47.311 billion, a decrease in its overall program level (-$368 million, or -0.8%) for the first time since FY2013.
The NIH already gets $47 billion per year, do you think they should get more?
That sounded almost too good to be true, especially with autoimmune stuff which seems even trickier to tackle than many cancers. One hell of achievement if it pans out long term.
I suffer from psoriasis. This seems like another 'solution' that really only addresses how the diseases manifest but not the root cause. I can go get a shot today that blunts my immune system, and my psoriasis will calm down for a year but I'll probably get a couple wicked chest colds.
Autoimmune diseases in no small part ruined my life. Forgive me if I seem rude, but I don't trust pharma to solve jack or shit without the correct financial incentives, and those proper financial incentives just can't organically exist for chronic sufferers of any novel disease.
> This seems like another 'solution' that really only addresses how the diseases manifest but not the root cause.
If you read the article, you'd see that one of the features is that in the vast majority of cases, the B-cells return, but not the B-cells that were causing the immunodeficiency
quote: "Once injected into the hosts, the CAR T cells got to work. They multiplied and targeted and destroyed all the B cells — including pathogenic cells linked to the autoimmune conditions. The bioengineered T cells survived for weeks in the recipients before largely vanishing. Eventually, new healthy B cells returned, but no pathogenic ones did. A similar response has been observed in people with autoimmune conditions who received CAR T cells derived from their own cells."
My point being that the immune system appears to remains functional with this treatment, differentiating it from the clinical therapies that are available to you currently.
Speaking as someone who has also been let down by the medical system, but also who wouldn't be alive without it: I agree that Big Pharma is a problem (anyone disagreeing with that is arguing against the scientific evidence -- Ben Goldacre's book Bad Pharma is a good introduction to the problems with the industry), and that in the gross case they are lacking financial incentives. At the same time, this does not mean that the clinical therapies we have or are developing, are utterly ineffective.
Could this work for chronic urticaria (autoimmune hives)?
Bye bye type 1 diabetes
In the future a pill with donor cells will be prescribed 1x a day for 3 days.
Depends. If it's up to bigPharma, it will be 1 pill 3x a day, forever. Chronic patients are the best to the bottom line
Keep an eye on sickle cell anemia cure then.
I thoroughly agree with your grayed comment. It doesn't necessarily imply that it's all greed and evil, but there's enough of it to dignify your statement, without applying my own experience.
It's a common misconception though.
There's nothing preventing pharma companies from just charging the equivalent of a lifetime supply for a one-off treatment. In fact, this is how cancer treatments are priced at the same time being the single largest source of revenue for pharma:
https://www.statista.com/chart/18311/sales-revenues-of-drug-...
I'm not directly arguing against this, but it seems to me that this would eliminate a large part of the 'survival market'. Incremental debt, paycheck to paycheck accounts for much of the population.
Personally, I'd rather explore Elysium than give the entirety of my already insufficient and all prospective funds to what I consider pharmaceutical pimps. Poverty in America is, in my experience, worse than much of the 3rd world, where the practice is often more salubrious, less stigmatized and better performed, depending on one's values.
My friend would have long been dead of hep-c had he remained in the US. Although the US is my home and I'll go nowhere else, he took advantage of his Aussie ancestry and obtained citizenship, relocated and was treated for free. Here it would have been at least 250,000.
On the subject of cancer treatment, notably in the US, I'll not argue the subject, but will directly offer my perspective, which views it as highly exploitative and financially motivated. One example is the absurd reluctance to embrace or iin some cases, explore, the subject of enzymatic therapies and other 'foreign' procedures.
I'm an incorrigible cynic here and not worth trying to educate.
Does this new donor-cell therapy potentially include the top-10 autoimmune diseases, such as rheumatoid arthritis, lupus (checked), and/or Hashimoto's thyroiditis?
Can I ask how “top 10” is defined? Is it the most common, or perhaps the most destructive to the individual?
I sorted by the most common, not the most destructive, but the key point is how 'easily' this could be extrapolated to other autoimmune diseases.
While the promise is great, let's be real. All of these personalised therapies get loads of funding because they almost inherently will be very expensive since they cannot scale, meaning drug manufactures supplying these can make a killing even compared to already expensive but more commonly used therapies. I guess this is more a comment on car-t usage in oncology and if this leads to seriously improved health outxomes, then of course, all the power to them.
Edit: i was mistaken, see below.
> very expensive since they cannot scale
This approach does scale, but has new safety risks.
They aren't genetically modifying each patient's own cells, one patient at a time, but are trying to create a line of generic T-cells that will attack only the B-cells of any patient.
The risk is that genetically modified T-cells that are not derived from your own cells might attack all the cells of your body, and not just your misbehaving B-cells.
They have made additional modifications to the CAR-T T-cells that they believe will prevent them from going rogue, but more safely testing is needed.
From what I've read, this same more generic approach is being attempted with CAR-T cancer treatment as well.
I understand this therapy is inherently more complex, but there are plenty of medical treatments that have helped millions of people without scaling like a drug: IVF, cognitive behavior therapy, casts for broken bones, etc.
Maybe I’m too optimistic but I’m sure the overall cost can be reduced dramatically over time even with individualization.
I'm not sure that I understand what you're saying.
These therapies are very individualized and will probably be very expensive.
How is CBT and casting a broken bone in any way like that? Those two things aren't reliant on medicine at all. Please explain, because I feel kind of stupid right now.
That’s the whole point here, it’s not personalized. It comes from a donor so it’s somewhat standardized.