First steps to a cure for a/i disease

[PMRpro]

I thought people might be interested in this article from the Guardian:

theguardian.com/science/201...

It isn't necessarily specific research on PMR/GCA that will make the difference but things like this that give us hope for a cure.

[Longtimer]

How interesting, once again discovering something that they weren 't looking for......shame for those patients, but hopefully it will be a start to the why's and wherefores of A/I diseases.....thanks for that.....

[Hidden]

Good research, sounds like the war of the worlds inside the body 🤣

[DorsetLady PMRGCAuk volunteer in reply to Hidden]

Certainly does, no wonder we get fatigued with all that fighting going on!

When everything’s working okay we don’t even give it a thought, but when things go wrong, it’s mayhem!

[Hidden]

Who or what orders & controls the various components of the immune system to act the way they do? Can't just be chemical messaging can it! Sorry for my ignorance how this works.

[PMRpro Ambassador in reply to Hidden]

Most things in the body ultimately work on chemical messengers! Hormones are chemical messengers, so are the cytokines we talk about in the context of PMR and GCA, interleukin-6 in particular. Tocilizumab/Actemra for GCA interferes in the cascade of substances, the pathway that results in the production of IL-6 - result, no IL-6 to cause the inflammation.

No need to apologise for ignorance - it's a whole different world with its own language and a scientist in one field doesn't fully "get" the language in another.

[Hidden]

interesting, but that's a mainstream newspaper article, written for the general public, over-simplify what is already known as if it's a new discovery.

[PMRpro Ambassador in reply to Hidden]

If you feel that is too simplistic have a quote direct from the horse's mouth:

crick.ac.uk/research/a-z-re...

where you can look at a load of the publications from the Institute.

But we shouldn't look down on a "mainstream newspaper article, written for the general public". We are the general public.

[ConventCassie]

I understood this to say that giving these cancer drugs led to type 1 etc. or could. I replied in a post earlier (may have been Facebook) that I turned down a cancer drug I was encouraged to take, because I thot they were experimenting on us. It sounds here like they are-In the least, gathering stats.

[Longtimer in reply to ConventCassie]

Lots of times I believe we are guinea pigs when it comes to medication....look what happened about the PPI (think it was AA) some people were taking for 10 years, now lowered it to 5 because of the results....years ago patients probably wouldn`t have refused things....now, lots of us check first (on here) and don`t treat the doctors/rheumies like gods.....thank goodness we do....

[DorsetLady PMRGCAuk volunteer in reply to Longtimer]

Hi

I’m sure patients are used as guinea pigs sometimes, particularly in cancer cases, and in some instances are told that beforehand, and to me that’s fine. They then have a choice as to whether they want to try a new drug.

If they aren’t told then maybe that’s not morally correct (I’m not the one to judge) but to play Devil’s Advocate, if the drugs aren’t tested on humans how do know if they are going to work successfully.

[PMRpro Ambassador in reply to Longtimer]

It isn't until any drug is released onto the market as safe and effective that the long term effects can be seen - clinical trials can't carry on for 20 years, no drugs would ever be developed if they did. In fact, when it comes to PPIs (omeprazole and co) it was said from the start they shouldn't be used for more than a few weeks at a time.

As regards alendronic acid, a bisphosphonate, similar drugs had been used for 50 years for something called Paget's disease and perfectly safely. The problem with AA was the manufacturers being greedy and claiming it was perfectly safe, so safe it could be given to everyone and there need never be an elderly lady dying of a fractured hip ever again - because that is a real factor, for the very elderly a fall can be a death sentance or at least the end of them living independently. They gave strict instructions as to how it should be used taken - patients ignored and doctors did not emphasise them and the result was gastric problems. Once that was cleared up, it seemed this was fine, the adverse effects were rare. They had forgotten that you don't find how rare (or not) until hundred's of thousands of patients are taking it.

[Longtimer in reply to PMRpro]

Sorry if I came over in my post as being ignorant or not understanding....

[PMRpro Ambassador in reply to Longtimer]

No - not at all. But it is something loads of people don't know about, how drug development goes on long after a drug is launched in the market. It isn't "experimentation", it is how it all works.

[ConventCassie in reply to Longtimer]

You’re absolutely right. We are advocating for ourselves and that is a good thing. I served on a Review Board for the Eleanor Roosevelt Institute (for cancer research) and we reviewed relevant NIH grants. It is critical that patients know if they are in a study or not. Lots of “populations” have been taken advantage of e.g. prisoners of war, anybody at Gitmo, and tribes of American Indians, blacks and prisoners. That’s why Review Boards now exist. I guess the rest of us have to fend for ourselves.

[PMRpro Ambassador in reply to ConventCassie]

That is what the article says - and what it means is that they can see how an autoimmune disorder happens in the first place as Type 1 diabtes and RA are triggered in some of the patients. I posted the link because people on the forums often lament "they" are doing nothing to find cures for PMR and GCA - and this is a group which now has the means available to look at HOW the immune system goes wrong. It may not mean a cure for PMR in particular - but they have to know what goes wrong before they can find a way of putting it right.

I don't know what drug you were offered, but when my husband had cancer he was put on a cocktail of drugs and warned that one of them, cisplatin, can and does cause loss of hearing. He woke up one morning some weeks later and realised things didn't sound as they had the day before. Over the years his hearing has deteriorated. At the time it was felt that without treatment he might be lucky to live a few weeks - 24 years on and he is still here. As he said at the time, "Deaf or dead? No contest is there?" Almost all drugs you are offered to "cure" nasty diseases are likely to show some unexpected or unwanted effects. But as for my husband, death or diabetes is a choice that shouldn't be difficult, especially when it is a rare side effect.

If you are offered an "experimental" drug as part of a trial then that must be explained to you. You will never be offered a drug that has not already shown it does something and does it as well as the current option. That would be unethical. Those drugs have usually been used in patients who have gone through every available treatment option and nothing is left to prevent their death except possibly this new "experimental" substance. If it then shows it extends their expected survival then it is added to the drug repertoire as a second or third line choice. Over time it proves itself to be useful - and it may be offered to patients to gain more information. The patient is monitored very closely - there is nothing to fear in Phase 3 clinical trials. Without them, there would be no new drugs.

[HeronNS in reply to PMRpro]

My stepmother's final husband was offered such a drug for I think COPD and it did indeed improve his life for a couple of years, although in the end the drug proved ineffective in the long term and he died. But what about those healthy young men left with life changing effects after just a dose of some new drug in a trial? They weren't people in need of final intervention. mirror.co.uk/news/uk-news/h...

[PMRpro Ambassador in reply to HeronNS]

That was the very first level of a drugs trial in humans. And the PRIVATE company who had the task did not obey the strict protocols and rules that are set up to minimise the risks of something like that happening. There were too many involved and the dose used was much higher than it should have been for the first test. They were also not being monitored properly, all of them were given the drug at the same time and there were not enough ICU beds available close enough. It was a catastrophe from beginning to end. They were also not patients - they were volunteers, mercenaries if you like. It was appalling, but not the same thing at all.

[HeronNS in reply to PMRpro]

So that means if you are in the sick about to die category you will not be in the first human trial? The drug will have been tested on healthy young men (almost always) first? At what point in the testing do they establish whether a drug is effective or safe for women and the elderly? Or do they? And how do they go about it? Would the kind of early offering of a new drug to a sick patient be the level where they are figuring out safe dosages, etc., or has that been done earlier? And on whom?

[PMRpro Ambassador in reply to HeronNS]

It will have been exhaustively tested on animals first for toxicity - for many things there are animal near equivalents though obviously a mouse or whatever is not the same as a human. There are protocols for establishing therapeutic doses but I don't know the details, I imagine they vary by the type of drug.

I don't know whether it is always healthy young men - maybe women are included too, I have never worked in Regulation. Some medications are never tested specifically in the elderly or in children - which is why care should be taken using drugs in over 75s in particular. The numbers involved in the various stages of drug regulation vary according to the type of drug. If you are developing a medication for a rare disease you obviously won't have as big a cohort and possibly not many of any given age group as if you are developing something like iboprofen for pain relief. The numbers involved increase at each stage - Phase 3 trials are the final level before release, tocilizumab passed its Phase 3 trials in 2016, now they are on Phase 4 where they monitor it in real life use. It is in Phase 3 that they establish whether it does what it says on the tin. Loads of drugs fail at that stage despite having been very promising on paper.

en.wikipedia.org/wiki/Phase...

So you can see why drug development is such a lengthy and expensive process.

[HeronNS in reply to PMRpro]

Thanks for informative reply. I believe one of the problems with drug testing, at least what I hear about which is probably USA, is the fact that men are the primary test subjects. Perhaps that is changing now. Certainly some attention seems to be being paid to the fact that women experience heart attacks in a very different, less definite, way from well known classic symptoms that men have, so maybe researchers are starting to acknowledge that we probably metabolize many drugs in a slightly different way.

[SheffieldJane]

Thank you for posting this. It gives me hope.

[sassyscript in reply to SheffieldJane]

Me too

[B4lamb]

Sounds like we need more T Cells to slow down our autoimmune system attacking our muscles.

[Rimmy]

Thanks PMRpro - any research around AI diseases is good to hear about - especially when there is so much competition for research $$. Some people one day (hopefully sooner than later) will no doubt hit on a key variable very relevant to us lot - but not holding my breath - just taking my Pred in the meantime as such things are always complex and drawn out - as we all know.

[yogabonnie]

So... is prednisone is stopping the immune system from attacking our muscles or is it just masking the symptoms? And if our immune system is compromised then could we be at more risk for cancer... or is our immune system also attacking any cancer that is floating about considering going whacko in our bodies?? ...Forgive my ignorance.. but you do seem to know so much I figured I'd ask this question!

[PMRpro Ambassador in reply to yogabonnie]

I suppose you have to say it is masking the symptoms - it is controlling the inflammation as a very potent anti-inflammatory drug. It also probably suppresses the immune system - but whether it suppresses the bit of the immune system that has gone wrong in PMR/GCA is another question. I doubt it somehow - whereas tocilizumab/Actemra does.

PMR/GCA doesn't directly attack muscles - it is a vasculitis, inflammation of the arteries supply blood, oxygen and nutrients to the muscles so it is an indirect not direct effect on the muscles. Long term uncontrolled inflammation in the body does increase our risk of developing various diseases including cardiovascular problems and vascular disease and some cancers. It is said that if we lived long enough the low level of inflammation that is thought to exist in all elderly people would eventually cause cancers. And it is also thought that cells are continually going "wrong" and start to divide and form tiny tumours but either something causes it to abort or they never get large enough to cause problems. That is one of the (rather poor IMHO) arguments against screening for prostate cancer for example - they say most PC tumours will never develop far enough to make the patient ill. But there is no way of knowing which are going to become aggressive - so is it wrong to treat a patient "just in case"?

[dartmoorlass in reply to PMRpro]

Are you saying that tociizumab/Actemra might be a good idea? It's been suggested as a possibility for me because I've had such a bad reaction to steroids - first 18 months to 2 years in or on bed or occasionally on a reclining chair, lost my independence and even now, 3 years on, each day is a challenge. Spirit it is more than willing but flesh isn't having any of it! To be truthful, it's only DL's story in addition to my previously, but fading optimistic nature that's giving me any hope of a reasonably normal Ancient Briton's (as my grandkids used to say) daily life at some future date! I don't like the idea of more medication but........

[PMRpro Ambassador in reply to dartmoorlass]

It is definitely worth considering IF your doctor can still access it now that NICE has its use in limbo. If it works it will remove most medications from the equaltion - and hopefully you will be a person where it gets rid of all pred, it doesn't always to be fair.

If I were in your position and offered it - I'd at least try it.

[Bj2016]

Thank you for posting this. I have PMR, my husband has MS and my daughter has Crohns, all three are AI diseases. As seems often the case, drugs developed for one disease throw light on another. Very interesting and a bit hopeful.