The Miracle of iPPS on MPS -Revisited

Well it's been quite a couple of weeks... How about I start this one off with a little humour...I need it as much as you!





Ok let's hit the ground running...



wo and half years later after I posted about the miracle of iPPS on MPS...I tonight, revisit and embellish on it..


It's a two part'er tonight, there is so much incredible evidence it just doesn't all fit into one post...


Please as always, do now enjoy!


THE MIRACLE OF IPPS ON MPS - REVISITED PART 1


RECAP

Back in in May 2021 I posted one of my most exciting posts (well I at least thought so!) on MPS and what exactly our drug is capable of.

Yes it has been a long 2.5 years...but this program has come along way too! We will get to that in a later in Part 2...lets' recap what I wrote back then to give the many many new guys to us, a briefing.

I referred to a paper that experimented on our Wonder drug on rats. (See Main reference at the end of Part 2)


Enzyme replacement Therapy (ERTs) is a major std of care for the MPS strains I, II and VI. There have been significant improvements in quality of life utilising ERTs however there is also some variability. How does it perform within the musculoskeletal domain?


"...the effects on cartilage and bone are modest".


The infused enzymes do not cross the brain blood barrier. Paradigmers, we already have evidence that iPPS CAN cross the barrier.

Researchers took MPS VI rats and treated them with Pentosan. The evidence was quite a read.

Tonight, a snapshot of the results from this incredible paper.


METHOD

Three groups of MPS VI rats were treated as follows:

GROUP 1 PPS given at beginning of 6 months of age


GROUP 2 PPS given at beginning of 1 months of age


GROUP 3 PPS given during prenatal development




So what happened?

What happened indeed!


Elevated levels of several serum inflammatory markers in ALL the MPS VI rats groups were reduced to near normal levels in the PPS-treated animals.

Now TNF-alpha is an inflammatory biomarker, you want LESS of this...


"Tumor necrosis factor alpha (TNF-α) is a cytokine that has pleiotropic effects on various cell types. It has been identified as a major regulator of inflammatory responses and is known to be involved in the pathogenesis of some inflammatory and autoimmune diseases".²


Yeah not good, we don't want elevated amounts of this, certainly in a chronic sense!


What was observed, ie what was the effect of PPS on this TNF-Alpha?

...the researchers put their observations like this:

"Reduced TNF-alpha levels also were observed in the livers, spleens and hearts by immunohistochemistry".


Lets just take a look at this via a pic.

In the below, TNF-Alpha was identified using a brown stain, the less brown the better...

There are three images below, the one on the left is the untreated rats...the other two images are two different samples representing the treated PPS rats:


Yes, the above figure is a sample from the heart tissue!




This is exactly what we want to see...PPS causing the TNF-Alpha to literally reduce...we want this done safely....as little side effects as possible...




Mate, the researchers also took articular chondrocytes at the end of the treatment period, grew it In Vitro and then analysed it....



Now look, I know there are going to be a number of you that say...Mozz, love your enthusiasm..but all I see above is some bl**dy dark grey bits that look a bit like moustaches on a bit of blotting paper...

Yeap - Let me point it out to you...


Seriously, can someone please calm me down...cos the market aint seeing what I'm seeing, are they that stupid?


_{Is anyone else going quietly nuts here?}



Ok sorry, I lost my cool there for a sec...I know there are corporate items we need to fix....there is revenue to be garnered...milestones still to be met...the reason why I'm getting so jumpy is cos I haven't even BEGUN to tell you about what else the researchers saw....
Let me continue...


These researchers were next level...they then began to investigate another part of the rats....I present to you....wait for it.....


THE TRACHEA

Now before you look at me funny and ask me how a trachea could be anything like as good as the heart in terms of evidence that we saw back there....let me just now ask you...what is the Trachea made up of?

Clues?



CARTILAGE !!

You should already know where this is going...


The researchers spent time examining the integrity of the tracheas...It is known that untreated MPS VI rat tracheas are generally collapsed by 9 months.

Look I don't want to get too emotional, but if you were the parent of a child that has a MPS strain and you know what's coming...wouldn't you seriously try anything that seems safe and that is providing even HALF the evidence and results as our PPS is showing?



What did the researchers find?

"In contrast, tracheas from the PPS-treated MPS VI rats were more open and the cartilage walls were thicker. Together, these results indicated that PPS treatment was reducing inflammation and increasing both articular and hyaline cartilage integrity in the MPS VI animals".


Yeah that's why I'm getting excited....pic?

Of course:




Yeah what you are literally seeing here is that Pentosan is widening up the openings of the trachea...this is profound.



MOBILITY

The researchers tested out the rats on a Rotarod...in summary they commented:

"MPS VI rats exhibited a markedly improved performance on an accelerating rotarod apparatus after PPS treatment".

But read the detailed evidence...


"This was evident at all speeds, but was most significant at or above 30 rpm, where the untreated MPS VI rats could not remain on the rotating bar. This behavior was further verified by observing the motility and appearance of the animals... treated MPS VI rats could stand on their hind limbs and were much more alert and mobile than their untreated littermates, and also had much smoother coats indicative of improved grooming".


Let's view this as a graph:


White boxes, untreated MPS VI rats; light gray boxes, group 1 treated MPS VI rats; dark gray boxes, group 2 treated MPS VI rats; and black boxes, group 3 treated MPS VI rats. The vertical lines in each column indicate the ranges. The dotted horizontal line depicts the length of time that normal rats could remain on the rotarod at all speeds (120 s). In each of the treatment groups there was a significant improvement in the rotarod performance compared to untreated MPS VI rats (*P<0.05). This occurred at all speeds. Note that at or above 30 rpm the untreated MPS VI rats could not remain on the rotating bar.




That concludes Part 1.

In Part 2 we take this up an entire level.

Huh? You mean there is more? Oh wait till you see Part 2...
It's also in Part 2 that we will also bring it home by way of an incredible bonus (just as I did in the original post 2.5 years ago) as well as setting the stage for what I hope to see soon perhaps in just a few weeks time?