testing for PSSM 2

[paddy555]

I don’t blame Valberg for refusing to work with EquiSeq - they were using her name and recommendations whilst refusing to share their evidence for what they claimed was a distinct genotype/phenotype.

Yes she has profited from the PSSM1 genetic test patent and from selling feeds - but the evidence for these was all published and peer reviewed so that people could make informed decisions about using them. EquiSeq have made a fortune and never given any evidence for their claims at all - when I asked them in 2017 they were adamant they were due to publish imminently and yet it’s never happened. It makes it look like they don’t have good evidence for what they’re selling.

Winger23man

can you please just answer this question. If in 2017 equisec were going to publish imminently and it is now 2024. That is 7 years later. My definition of imminently is a little less than that.

do they not have the evidence and therefore cannot publish,
are they scared it will not stand up to scrutiny

are they making too much money without publishing which means desperate horse owners are testing with no peer reviewed back up. Snake oil salesmen in other words.

we don't need you to go into any more detail just tell us why?

many of us are novice horse owners when it comes to PSSM2 or whatever else it may be. So we listen to people who can help us.
On here it is Shortstuff and khalswitz. People who work daily in this sort of area.

Why should we listen to you rather than them?

what are you qualifications in this area?

someone less generous than me may even think you are on commission from equisec.

 

[khalswitz]

It’s Valberg who refused not the other way round and there is evidence to prove that too. Can you prove your statement perhaps Valberg would comment herself

Yes a muscle biopsy is the gold standard in medicine however it isn’t fool proof as Valberg herself admits

You will not find the disease by muscle biopsy in a healthy young horse

DNA has advanced over the years

Yes, I literally said Valberg refused. A variety of researchers have tried to work with or discuss research with EquiSeq - RVC, Minnesota, UCDavis, and others - and every person I have discussed this with including myself (some of whom I have even seen the written correspondences) has similarly not been shown any evidence when they have asked EquiSeq for it. When no one with a good reputation wants to work with them, that’s not a conspiracy.

No, biopsy samples are not fool proof. But they are the best we have, and can illustrate a variety of physiological problems in the muscle. And using ‘muscle biopsy is not fool proof’ as a defence for a test that hasn’t even got evidence of disease association is really quite hypocritical.

And yes you can. I personally have seen signs of exertional myopathy (because PSSM2 is so nonspecific and we don’t really know for sure it’s distinct from RER/ exercise-associated myopathy syndrome more widely) in samples from a large number of horses as young as 2 - what is more associated with severity of disease state on histology is athletic use. So many horses nowadays aren’t broken til 5 or 6 and then never work hard, so it takes longer for accumulation of mild muscle disease signs than horses that do - and we’ll only see the samples when they are older and have been in work. Considering we don’t even have a distinct, clear disease phenotype for PSSM2, lots of caveats have been added to any claims about age made in the literature.

Equiseq has made a fortune with the commercial selling of these tests and were at fund raising roadshows raising investor capital.

Irrespective of whether Valberg is interested they should have the funding to do the research. It was 2-3 years ago that Paul said they'd produce a paper on the k1 variant. It is pretty catastrophic in humans and would show on biopsy - so if it affects horses then it should show on biopsy.

This is a huge issue with these tests. If we see absolutely nothing on biopsy, and it’s not because the horse has never been symptomatic (in which case you wouldn’t know anything is wrong) or because the wrong muscle has been biopsied etc, then we’d expect to see at bare minimum signs of historical muscle damage and repair cycles in a horse with myopathy.

The diseases that these have been compared to are devastating in humans, and the muscle biopsy sample appearance is severe. With PSSM1 the appearance is usually very obvious histologically unless the horse is very young and heterozygous. Why would functional mutations in any of these genes produce such a mild phenotype as to be nonexistent histologically whilst producing such severe clinical signs when handled and ridden? It makes no logical sense and no evidence has been provided.

 

[I'm Dun]

Winger23man

many of us are novice horse owners when it comes to PSSM2 or whatever else it may be. So we listen to people who can help us.
On here it is Shortstuff and khalswitz. People who work daily in this sort of area.

Why should we listen to you rather than them?

what are you qualifications in this area?

someone less generous than me may even think you are on commission from equisec.

someone might think his name was Paul, I mean not me, but someone might...

 

[Fieldlife]

someone might think his name was Paul, I mean not me, but someone might...

It's pretty obvious he is Paul.

 

[Winger23man]

There is research it

I was pro the type 2 test, until it turned out there was no research to be published by the company, and there is literally nothing linking these genes to any sort of diseas

 

[Winger23man]

There is research it

There is research and it’s published what you are referring to is peer reviewed research this will take years as it’s not that straightforward. My point to you is that Valberg has refused to work with the commercial companies doing their own bungled research and decided mim doesn’t really exist in anything but warmbloods

I state again why hasn’t Valberg worked with the dna companies undertaken their own biopsies on the horses identified as symptomatic by dna. Compared notes even if it’s only to blow the theory out of the water. Why because the gold standard gives all the answers when they know it does not and Valberg admits biopsy can be negative

Really makes no sense not to pull together however Valberg test makes the vets lots of money dna makes them nothing

Anyway we have an admission on this thread that the dna does highlight the disease but what it never set out to do is say the horse is symptomatic as a result. The way forward is the two sides work together however vets are so blinkered they wont

 

[Winger23man]

someone might think his name was Paul, I mean not me, but someone might...

Ready the rubbish on here are you happy to listen to these so called educated people. If so crack on I have an open mind

 

[shortstuff99]

No we don't, I said genetics can tell you what gene regions are present. THIS IN NO WAY SAYS THAT THE DISEASE IS PRESENT. I can link anything I feel like to a gene region, say COX1 makes rabbits like carrots, and every rabbit with that gene likes carrots. Doesn't make it true. You can do some pcr on a rabbit sample for cox1 and find it. Still isn't true.

And if it takes you over 10 years to publish a study in a scientific journal that you've completed then your study is sh*t.

 

[Winger23man]

Yes, I literally said Valberg refused. A variety of researchers have tried to work with or discuss research with EquiSeq - RVC, Minnesota, UCDavis, and others - and every person I have discussed this with including myself (some of whom I have even seen the written correspondences) has similarly not been shown any evidence when they have asked EquiSeq for it. When no one with a good reputation wants to work with them, that’s not a conspiracy.

No, biopsy samples are not fool proof. But they are the best we have, and can illustrate a variety of physiological problems in the muscle. And using ‘muscle biopsy is not fool proof’ as a defence for a test that hasn’t even got evidence of disease association is really quite hypocritical.

And yes you can. I personally have seen signs of exertional myopathy (because PSSM2 is so nonspecific and we don’t really know for sure it’s distinct from RER/ exercise-associated myopathy syndrome more widely) in samples from a large number of horses as young as 2 - what is more associated with severity of disease state on histology is athletic use. So many horses nowadays aren’t broken til 5 or 6 and then never work hard, so it takes longer for accumulation of mild muscle disease signs than horses that do - and we’ll only see the samples when they are older and have been in work. Considering we don’t even have a distinct, clear disease phenotype for PSSM2, lots of caveats have been added to any claims about age made in the literature.



This is a huge issue with these tests. If we see absolutely nothing on biopsy, and it’s not because the horse has never been symptomatic (in which case you wouldn’t know anything is wrong) or because the wrong muscle has been biopsied etc, then we’d expect to see at bare minimum signs of historical muscle damage and repair cycles in a horse with myopathy.

The diseases that these have been compared to are devastating in humans, and the muscle biopsy sample appearance is severe. With PSSM1 the appearance is usually very obvious histologically unless the horse is very young and heterozygous. Why would functional mutations in any of these genes produce such a mild phenotype as to be nonexistent histologically whilst producing such severe clinical signs when handled and ridden? It makes no logical sense and no evidence has been provided.

This is where you are wrong. If the horse is not in a dieased state or the disease has not progressed due to age it won’t show as you claim. Also if bets get the sample wrong which they do you haven’t got a hope in hell of seeing muscle damage

 

[Winger23man]

No we don't, I said genetics can tell you what gene regions are present. THIS IN NO WAY SAYS THAT THE DISEASE IS PRESENT. I can link anything I feel like to a gene region, say COX1 makes rabbits like carrots, and every rabbit with that gene likes carrots. Doesn't make it true. You can do some pcr on a rabbit sample for cox1 and find it. Still isn't true.

And if it takes you over 10 years to publish a study in a scientific journal that you've completed then your study is sh*t.

Do you actually understand how complex the process is. Pssm1 was straight forwards even if Valberg has confused Mim with pssm2. We are talking about 6 variants not one and there are two recently discovered new ones along with a load of unknown ones. With anything even humans there are undiscovered muscle disorders. You make it sound so easy

 

[khalswitz]

This is where you are wrong. If the horse is not in a dieased state or the disease has not progressed due to age it won’t show as you claim. Also if bets get the sample wrong which they do you haven’t got a hope in hell of seeing muscle damage

I’m wrong, and all of the biopsy submissions where I have seen exactly that, evidence of muscle damage in young athletic horses, and all the published reports going back even before the 90’s of exercise related muscle damage in racing thoroughbreds as young as 2, is all a hallucination? The known muscle repair physiology timeline is a lie?

I’m tapping out here before I say something I regret. If anyone else has genuine questions I’m happy to reply but there’s no point arguing with trolls.

 

[shortstuff99]

Do you actually understand how complex the process is. Pssm1 was straight forwards even if Valberg has confused Mim with pssm2. We are talking about 6 variants not one and there are two recently discovered new ones along with a load of unknown ones. With anything even humans there are undiscovered muscle disorders. You make it sound so easy

Yes, I am a published geneticist, are you?

It is complicated hence, why it is disingenuous to claim that these gene regions are indicative of disease when no one has been able to show it and charge money for it.

I absolutely believe there are unknown muscle disorders in horses, and I'm fully behind trying different management regimes. But I draw the line in trying to get desperate owners to spend 100s of pounds for a test that shows them nothing more than they already know.

 

[Tiddlypom]

.

I’m wrong, and all of the biopsy submissions where I have seen exactly that, evidence of muscle damage in young athletic horses, and all the published reports going back even before the 90’s of exercise related muscle damage in racing thoroughbreds as young as 2, is all a hallucination? The known muscle repair physiology timeline is a lie?

I’m tapping out here before I say something I regret. If anyone else has genuine questions I’m happy to reply but there’s no point arguing with trolls.

Thank you khalswitz, your contributions are invaluable. You are flushing out the bad science and the troll doesn’t like it.

 

[paddy555]

I’m tapping out here before I say something I regret. If anyone else has genuine questions I’m happy to reply but there’s no point arguing with trolls.

I quite understand but thanks as you have provided a lot of info. I'm others are also grateful

Winger23man

if we are to take you as other than a troll we. need at least your qualifications. Presumably as you didn't answer my comment about this you don't have any. Is that correct please?

 

[paddy555]

someone might think his name was Paul, I mean not me, but someone might...

deary me I'm Dun. But as you say not you.

 

[khalswitz]

.

Thank you khalswitz, your contributions are invaluable. You are flushing out the bad science and the troll doesn’t like it.

I quite understand but thanks as you have provided a lot of info. I'm others are also grateful

Winger23man

if we are to take you as other than a troll we. need at least your qualifications. Presumably as you didn't answer my comment about this you don't have any. Is that correct please?

Thanks guys, this is a topic I’m hugely interested in and there is so much interesting chat to have about it - always happy to discuss genuinely!

 

[FieldOrnaments]

It's pretty obvious he is Paul.

Who is paul?

 

[Tiddlypom]

Who is paul?

There’s enough clues in the thread to Google the answer to this.

 

[FieldOrnaments]

got it

 

[FieldOrnaments]

shortstuff and khalwitz thank you so much for your hugely informative contributions they are really invaluable and much appreciated

 

[nutjob]

My point to you is that Valberg has refused to work with the commercial companies doing their own bungled research and decided mim doesn’t really exist in anything but warmbloods

But if you feel that way about Valberg and you are ridiculing all other scientists working in the field then surely your company er I mean Paul's company wouldn't want to work with them anyway. If these scientists are bungling their research and confusing MIM with PSSM2 what would they bring to the table when equisec are so sure they are correct and everyone else who doesn't believe them without seeing evidence or data is narrow minded.

I wonder why equisec don't publish their findings and data, or commission independent researchers to confirm their hypotheses.

 

[SEL]

Thanks guys, this is a topic I’m hugely interested in and there is so much interesting chat to have about it - always happy to discuss genuinely!

The frustrating thing for me if that there was genuine research going on I'd offer up a muscle biopsy from my symptomatic p1 mare who I suspect has more going on than just P1. But I'm not paying £100s for an unproven set of tests which don't really tell me what is actually going on in the tissue.

I also wonder that if the nutritionist who is seeing results supplementing manganese has just found some horses don't absorb it well and their positive Equiseq results are purely incidental

 

[khalswitz]

The frustrating thing for me if that there was genuine research going on I'd offer up a muscle biopsy from my symptomatic p1 mare who I suspect has more going on than just P1. But I'm not paying £100s for an unproven set of tests which don't really tell me what is actually going on in the tissue.

I also wonder that if the nutritionist who is seeing results supplementing manganese has just found some horses don't absorb it well and their positive Equiseq results are purely incidental

I’m not affiliated with this research in any way, but I’m aware the University of Minnesota (Molly McCue’s group) were running a large project collecting genetic material and health data from a large number of horses. If the project is still recruiting that could be a good one to look up if you’re interested!

 

[Winger23man]

I’m wrong, and all of the biopsy submissions where I have seen exactly that, evidence of muscle damage in young athletic horses, and all the published reports going back even before the 90’s of exercise related muscle damage in racing thoroughbreds as young as 2, is all a hallucination? The known muscle repair physiology timeline is a lie?

I’m tapping out here before I say something I regret. If anyone else has genuine questions I’m happy to reply but there’s no point arguing with trolls.

You clearly haven’t read up with Valberg. Whilst you are being “trolled” don’t forget to keep up. Modern trolls are friendly!

 

[paddy555]

. Modern trolls are friendly!

I'm sure they are just in your case totally unqualified it appears.

 

[SEL]

I’m not affiliated with this research in any way, but I’m aware the University of Minnesota (Molly McCue’s group) were running a large project collecting genetic material and health data from a large number of horses. If the project is still recruiting that could be a good one to look up if you’re interested!

I tried to be a part of that but they needed a comparable pssm negative horse. My other horse then was homozygous (asymptomatic) so I wasn't eligible.

They kept asking me if they were on the same diet - obviously they weren't because one was horrendously symptomatic and needed all the supplements!

 

[khalswitz]

I tried to be a part of that but they needed a comparable pssm negative horse. My other horse then was homozygous (asymptomatic) so I wasn't eligible.

They kept asking me if they were on the same diet - obviously they weren't because one was horrendously symptomatic and needed all the supplements!

Useful to know, thanks for feeding back!

 

[Exasperated]

It’s Valberg who refused not the other way round and there is evidence to prove that too. Can you prove your statement perhaps Valberg would comment herself

Yes a muscle biopsy is the gold standard in medicine however it isn’t fool proof as Valberg herself admits

You will not find the disease by muscle biopsy in a healthy young horse

DNA has advanced over the years

When I suggested this to our equine vet; who did NOT favour biopsy for suspect PSSM 2 (invasive, false positives, false negatives, etc, etc); replied: ‘Yes, it’s the standard test, but solid gold it ain’t, believe me’.
That doesn’t mean biopsy has no value, nor that genetic tests hold the answers, rather that far more, and far more open-minded (rather than polarised) research is required.
By the way, did anyone ask about the Liverpool Uni project?

 

[I'm Dun]

I’m not affiliated with this research in any way, but I’m aware the University of Minnesota (Molly McCue’s group) were running a large project collecting genetic material and health data from a large number of horses. If the project is still recruiting that could be a good one to look up if you’re interested!

they had samples from both of mine a couple of years back.

 

[Winger23man]

Wrong but in your case totally blind and unwilling to think outside the box.