How far away is a treatment that stabilises this disease?

[FlexyWex101]

Young guy here (26) who has suspected motor neurone disease. Obviously, the prospect of having MND is devastating but from what I read we might be on the cusp of some real progress in MND research and treatments. AMX0035, which apparently grants an additional 6 months over a 2 year period, could well be available by the middle of this year. T-REGs may also make a dent. Am I naive in thinking there are reasons to be optimistic, and that treatments that dramatically slow this disease will be available shortly?

[Cat lady]

I don't think it's being naive at all. We have to have hope.

[Onein300]

The general consensus is that we are within a couple of years of treatments for some members of our community. The amount of research has exploded. Once the first breakthrough happens, money will pile into the disease as we would have shown it's treatable.

No one knows tomorrow !

Best wishes
Lee

[FlexyWex101]

The general consensus is that we are within a couple of years of treatments for some members of our community. The amount of research has exploded. Once the first breakthrough happens, money will pile into the disease as we would have shown it's treatable.

No one knows tomorrow !

Best wishes
Lee

Thanks for getting back to me Lee, and I hope you're doing well. Sorry to press but when you say 'some members of our community', I assume you're talking about those with known genetic causes e.g. SOD1, FUS and others. It seems like they've been on a verge of a gene therapy that might arrest the disease in those groups for a while now and that they're getting close. It won't benefit me personally I doubt but for their sakes, I hope it comes soon. Have you any thoughts on things like T-Regs? Those had some impressive Phase 1 trials, but of course it was just 3 people they tested and its very possible the slowed/stopped progression was like a fluke or placebo effect. It seems as though there's interesting research being conducted in autoimmune and stem cell fields in particular but also that it's unclear how much will actually come of it: as I understand it the MND community has a tragic history of being teased with treatments which appear to be effective in early trials but then fail more detailed studies. And of course,as a layperson it's difficult to find anyway to get reliable updates on how research is going. Companies have an incentive to spin their results as positively as possible. Practicing neurologists are often out of the loop of really cutting edge research.
Best wishes,
Flex

[Onein300]

Thanks for getting back to me Lee, and I hope you're doing well. Sorry to press but when you say 'some members of our community', I assume you're talking about those with known genetic causes e.g. SOD1, FUS and others. It seems like they've been on a verge of a gene therapy that might arrest the disease in those groups for a while now and that they're getting close. It won't benefit me personally I doubt but for their sakes, I hope it comes soon. Have you any thoughts on things like T-Regs? Those had some impressive Phase 1 trials, but of course it was just 3 people they tested and its very possible the slowed/stopped progression was like a fluke or placebo effect. It seems as though there's interesting research being conducted in autoimmune and stem cell fields in particular but also that it's unclear how much will actually come of it: as I understand it the MND community has a tragic history of being teased with treatments which appear to be effective in early trials but then fail more detailed studies. And of course,as a layperson it's difficult to find anyway to get reliable updates on how research is going. Companies have an incentive to spin their results as positively as possible. Practicing neurologists are often out of the loop of really cutting edge research.
Best wishes,
Flex

Flex,

Hi there. Yes I am good thank you. I march on still!

Before I respond it's important to note that all experimental treatments are just that until one or more is proven and then approved. As you say, there is a lot of overstating progress in some quarters!

The most likely treatments to come to the fore will always be those that have a solid scientific and plausible modes of action. With SOD1 cases of MND we have over 30 years of knowledge and now we have a solid consensus that toxic build up of aberrant SOD1 proteins is highly involved in the disease triggering and or progression. Despite the reported Phase 3 failing of Tofersen (primary endpoint) the ongoing open label extension OLE (which is run under full trial conditions) showed very very promising signs after the short placebo period. In my opinion if the placebo controlled period had been longer this would have been perhaps clearer earlier. However, the OLE is still ongoing and it will be fascinating to see the results probably this year. They have about 3 years of OLE data I believe! That is some data. Compare that to the short 7 months of data a certain other highly published treatment has!

Gene therapies for the other the gene mutation causes will be the most likely first truly effective therapies.

BUT IMPORTANTLY, this does not mean that only the known associated gene mutation caused cases can be treated by gene therapy. There are at least 2 gene therapy trials underway for sporadic MND. Eg Ataxin, NRF2 etc.

A lot of people mistake gene therapy as only being of any use for familial cases.

This is NOT the reality.

Gene mutations are probably responsible for a lot more cases, and there is even evidence, for example, that knocking down the SOD1 gene might have positive effects for even non-SOD1 caused cases. Remember our genome changes as we age and genes control everything, not just inheritance.

The TREGS trial in the USA is very early doors and yes has no weight yet, with 3 cases in phase 1 it was only a short trial and the results could be purely within the natural history of the disease. There are other ways to boost tregs, rather than the complicated and burdensome technique under investigation in the USA, eg with drugs etc. The Mirocals Interlukin 2 trial has just ended and I am keen to see the results of that. If that has good results it would be a lot cheaper, less burdensome method of boosting tregs.

Stem calls are a "sound bite" and the majority of researchers don't believe stem cells are a viable therapy approach for MND. It's why you see not much enthusiasm for them, as the mode of action of stem cells for MND is near science fiction in replacing up to 1 metre long cells. I certainly have no belief in such an approach.

Importantly we have lots of targets now, and we are getting closer.

I do not agree with your statement regarding practicing neurologists. The majority are fully aware of where progress is, and as I say everything is experimental until proven and then approved. So largely our neuros advise the best course currently.

If you ever have any questions or have doubt in something you have heard, you should always contact the MNDA to ask.

How can I put it? Please don't believe everything you might read on Facebook, social media and twitter from some campaign groups. Always go to an association like the MNDA. They are world class, and although they might not say want we want to hear, they do have their finger on the pulse and have a solid scientific background etc.

And remember, as I have said, boy are we in interesting times for our disease!

Keep the faith.

Lee

[Banned]

I still don't know what kind of MND I have got! I would settle for just that before the end of 2023!

[Johnny5]

It is human nature to survive, we keep the faith because we want to live. Frustration of purpose is another story.

Common sense is under utilized it seems. I presented the same question to several researchers...Are there any studies on longevity comparing pALS who survive 10-20 years vs those who are gone in 2 or 3? Seems as if studies on comparison would point to whatever causes 5% of us to survive 20 years. If they find why those 5% survive so long, then they could develop treatment to change the course of this disease and provide a substantial extension of survival for the rest of the 90%. All I get are illogical answers about the necessity to test drugs on fast progressing, qualified clinical participants. There is no common sense in shooting in random directions to hit a target when you don't know where the target is. There are more living human lab rats with MND/ALS that would volunteer for this study than we have patience. Sometimes I think they spent more making genetically alterations in mice than they have in curing this disease.

[FlexyWex101]

It is human nature to survive, we keep the faith because we want to live. Frustration of purpose is another story.

Common sense is under utilized it seems. I presented the same question to several researchers...Are there any studies on longevity comparing pALS who survive 10-20 years vs those who are gone in 2 or 3? Seems as if studies on comparison would point to whatever causes 5% of us to survive 20 years. If they find why those 5% survive so long, then they could develop treatment to change the course of this disease and provide a substantial extension of survival for the rest of the 90%. All I get are illogical answers about the necessity to test drugs on fast progressing, qualified clinical participants. There is no common sense in shooting in random directions to hit a target when you don't know where the target is. There are more living human lab rats with MND/ALS that would volunteer for this study than we have patience. Sometimes I think they spent more making genetically alterations in mice than they have in curing this disease.

I rather share your frustrations, Johnny. Smart though undoubtedly many researchers are, they also seem to be very blinkered and working to outdated paradigms. An example: in the past few years, more and more studies are rolling out which suggest that ALS is predominantly(and certainly in a good number of cases) a disease of the neuromuscular junction and the axons, that problems arise where the neurones interact with the muscles and then the motor system 'dies back'. Nerve biopsies are a low risk procedure that allow for this area to be scrutinised in intense detail, researchers could see abnormal protein aggregations, for example, or changes in gene expression (and indeed some already have, in labs) and with a decent amount of sufferers and controls they could flag abnormalities pretty quickly, yielding new targets for therapies. Yet this research isn't happening. Individual researchers and labs have made their names and earned significant amount of grants faffing around with stem cells and focusing myopically on the neurones (which animal studies have shown, even if you preserve them do not prevent symptoms and ultimately death since axon decay still occurs, so the neurones can't connect to the muscles), procedures which have so far yielded few results, and are almost certainly a dead end. But they're committed now; they've tied their research stars to that direction and it'll take a miracle to get them to shift focus. Meanwhile, ALS patients are dying, with no treatments anywhere to be seen. It's maddening.

A lot of shady stuff seems to go on at the interface of researchers, investors and bringing a product to market too. Leaving aside the issue of the difficulties of jumping through regulatory hoops and excessive red tape, a lot of biotech companies just simply do not seem to operate in good faith. I've recently been very disappointed in Coya Therapeutics, the company that is developing Dr Stanley Appel's idea of injecting ALS patients with T-Regs. Dr Appel suggested years ago that in fast progressing ALS patients there tends to be low and dysfunctional T-Regs, and that a faulty inflammatory response is implicated in progression. However, now evidence suggests that inflammation is probably a very small part of ALS and not applicable to many patients - it certainly doesn't drive decline. Coya read research, they must know this, yet they're doing interviews talking about ALS as though it is predominantly inflammation driven, and touting their treatment as a possible cure. And what is there to show so far? A 6 person study (if I recall correctly) with very ambiguous results. Probably beefing up T-Regs does something, but I can't see it buying any more than a few months, and that's in people with high inflammation. In ALSers without that they'd be better off drinking sparkling water.

[John D]

The easiest and probably most reliable way of keeping up with research is via the MNDA’s research pages and subscribing to their monthly Newsletter - https://www.mndassociation.org/research/

Onein300 Lee - Any progress in obtaining the £50m from the Government?

[Onein300]

John D Hi there.

re the £50m project please take a read of our update here

https://patientsunited2endmnd.org/2022/02/07/status-update/

We will updating further soon.

Subscribe to our website to get updates. We will be updating at least monthly.

https://patientsunited2endmnd.org/subscribe/

With regards to TREGs they have been implicated for years, and Coyas attempt at boosting is one attempt, but in my opinion a bit of a sledgehammer to crack a nut. Not only does it involve a rather complex and risky procedure, it involves out of body processing and re injection.

But there are many ways to boost and target TREGs, including drugs like Interlukin 2 which has just finished trials in the trial Mirocals. We are expecting results very soon. Yes it's unlikely to be a game changer, but if successful would provide a simple way to boost TREGs.

MND research has vastly progressed in the last 5 years and targets have solidified. In addition gene therapies are starting to breakthrough, and probably Tofersen is still very likely to be the breakthrough drug for sod1.

At the same time there are at least 3 other gene therapies ongoing in trial including 2 for sporadic MND.

Genetics is probably ultimately the reason why some people progress slower, for example the common variant unc13a has good evidence for a protective gene/progression speed.

Science has to take the lead, and despite our plight just simply rushing unproven drugs to market is not the best strategy.

My personal ethos is that we must do nothing that potentially slows or delays the arrival of eventual truly effective treatments. I for one would want a treatment available before my son gets older! Trials are largely an altruistic act and we must think of those to come. We will save more lives by being very analytical and using solid regulations.

Best wishes

Lee

[Johnny5]

It is hard to justify shooting at a target if you do not know where the target is. A long-term progressive study on longevity to identify what exactly is the difference between those who survive 10-20 years vs 2-3 years should identify what the target is.

Just shooting in the dark has done very little for decades. If what they are doing is not/has not gotten results, it is time to change the way they do it. Simple logic and common sense, nothing out of a book.

[Banned]

I agree Johnny.

I have defeated MND, with the battle scars, yet science is not the slightest bit interested how I have done it! It is as if I have patented something!!

[EvelynMW]

i got turned down for resaerch because my progression is too slow! I was happy to hear that at the same time as being slightly annoyed.

[neil m]

I have been taking Tudca every day since AMX 00035 was shown to reduce the progression, AMX 00035 is 50% Tudca and 50% Sodium Phenylbutyrate which is very expensive.
you can buy Tudca on Amazon btw.
I take the same dose that showed statistically significance ie 2 grams a day.
should AMX become available then il add the other part.

[neil m]

I agree Johnny.

I have defeated MND, with the battle scars, yet science is not the slightest bit interested how I have done it! It is as if I have patented something!!

Hi Graham
are you being serious? If so how did you do that?