"You'll have time to rest when you're dead."- Robert De Niroith...

"You'll have time to rest when you're dead."

- Robert De Niro



ith so many topics to write about in regards to PAR, it's kinda like I can't let my mind wander too far as I will just not be able to stop with the new topics... I kinda feel like the above quote applies and that will be my life for the next x years following the best stock's story (my opinions) that I've come across so far... But as I say, it's a labour of love and having YOU to write for, well it's worth it and sure, I learn as I go too.

Speaking of learning's, sure we can watch a video and it gives us some good info...but I want to embellish it...I want to really associate this with us. Yes I'm talkin' about makin' it personal....that was my Robert De Niro accent.




_{Are you talkin' to me? Are you writing to me? Are you posting to me?}


It's one thing to learn in the newspapers that good ol' Afterpay is bought out for a record amount...it's another thing to BE an afterpay shareholder and experience the story from day dot. Paradigmers, I believe WE are at the cusp of something great and though some of you may think you are a bit late to the party, no way....you are early. Yes this is a story of patience, of steel type nerves....of hurdles we have to pass, twists and turns along the way.

An investment in a Bio Pharma is never without some drama.

This post is predominantly based on the MPS forum and thanks to @Robbie1 for bringing it to our attention.

Tonight you will hear of some amazing and fascinating evidence. We will investigate some new biomarkers...we will hear of a new organ not previously thought of as accepting of the PPS molecule and you will come across the Mozz Trojan Horse theory....I promise to show you some pics that will blow a few of you away. Yes I will do my utmost to keep away from long scientific names and will also promise not to bore you crazy. Do try and read it as it will give you clear insight on just why I believe we have made a good investment as we peek under the hood and stay ahead of the uninformed, more fleeting shareholder. (My views)

As always, please now enjoy.


PART 1

INTRODUCTION

This was one eye opener of a video dealing with Pentosan and it's amazing effect on MPS patients.

Lets begin with a definition or two....What is a GAG?Well no @Absentfriend not in the joke sense...I mean biology-wise.

GAGs stand for Glycosaminoglycans (GAGs), also known as mucopolysaccharides, thats where the MPS disease acquires its name. Every mammal has these GAGs in their cell tissues.Now the function of these GAGs were initially thought to be limited to ¹ :


- Cell Hydration


- Structural scaffolding



An advance in research now alludes to the above functions along with them playing a key role in cell signalling and this in turn modulates a vast amount of biological processes. Now I start to understand just how and why a patient of Mucopolysaccharidosis is unfortunately affected in so many terrible ways.

Paradigmers, I'm here to make a buck, but heck, if we can deliver some first time real relief to these guys, we are going to make some headlines for all the right reasons let me tell you.


THE ROLE OF INFLAMMATION

There is evidence that GAGs "...may be involved in limitation of the inflammatory response and, in particular, regulation of cell adhesion and trafficking". ¹ What I didn't also know and learned from the video is that these GAGs are primarily responsible for ongoing inflammation, "its turned on but never turned off!". Herein lies the problem.

Dr Lilla Simonaro from the Icahn School of Medicine at Mount Sinai, New York gave a most amazing presentation of the findings, let's explore.

Now the goal of Dr Simonaro's lab was to investigate new therapies that can be used in ALL patients.Just one bit I loved about this video is that it consisted of not one aspect...but three:

MPS IIIA Mice - focusing on Brain disease

MPS VI Rats - focusing on Skeletal Disease

MPS I Dogs - Focusing on Cardiovascular disease



So what links all of the above?

Correct, Inflammation pathways...


What drug that YOU know about, that I know about, but the market in general DO NOT know about...?

Yes correct again, iPPS.



_{(You are getting good at these sort of tests aren't you?)...I hope we all get our A+ 's in less than a couple of months time and celebrate the opening of our you know what....}



So it is these Inflammatory pathways that are rendered defective due to the GAG accumulation.



THE ROLE OF INFLAMMATION IN MPS

As a starting point the researchers compared a normal mouse to one that had inflammation, the findings were stark. The big clue here is what is referred to as a 'double knock out'...



_{A mouse double knock out? Err.... not quite like the above pic.}


The researchers took three sets of mice:

1. Normal mouse
2. Mouse with MPS and inflammation
3. Mouse that was bred with a defect that prevents it from having inflammation with a MPS VII mouse, this is called a double knock out (DKO) It's a mouse that has MPS VII but NO Inflammation.

Ok enough sciency words, how about a pic!

Now for the amazing stark results. In figure A below you can see the three mice lined up. Take a look at the snout of the DKO, it's visibly shorter than the normal mouse but not as bad as the stature of the MPS VII. This is Inflammation at work which hampers the MPS VII mouse.




_{Figure A - Comparison of statures of mice}


Let's take a look at the inside bone structure of the same mice, taking a look at the skeletal femur X-ray...again, the DKO not too bad, but add some inflammation (MPS VII below)...and again....its bad:





_{Figure B - A step down, looking at femurs}


Shall we go one step deeper? Cellular level?


Finally a pic of the GAGs accumulation, the first time I'm seeing this:





_{Figure C - One more level lower...the GAGs.}


In the above figure we can see the larger white swollen cells are the GAG accumulation, we want less of these ...normal mouse on the left, MPS VII in the middle and Double knock out on the right.


So according to the researchers, these are some of the INCREDIBLE effects Pentosan has on inflammation:

• Improvement of Skeletal and Cartilage Abnormalities
• Improved Cardiovascular system
• Action on collapsed tracheas, making them more rigid, more stiffer and most importantly, more open
• Increase in range of joint motion
• Addressing loss of mobility
• Positive effect on pain
• Reduction of Neuroinflammation

BUT as Dr Simonaro reported, they found an additional surprising result......GAG reduction...and it was much more dramatic when PPS was delivered SubQ as opposed to oral administration.



BELL CURVE


Remember this one?If you are new to us...I believe the efficacy of iPPS follows a typical bell curve. What I mean is my Home Economics teacher back in Year 7 was right.

Huh?

In cooking class she used to always go around the room and in her Italian accent she'd always say while clapping her hands "Add a liddle at a time" she meant add a little salt but sparingly, not too much...she'd almost sing those words...In the very same way Paradigmers...there is a balance between dosing....too little and you don't get much bang.....too much and the bang is deafening and you start to get a poor result.....you need it to be just right and in Mozz terms I'm guessing the amount is close to 2 mg/kg.

Here is a bell curve....we want that peak balance. Those little greek characters across the X axis represent standard deviations. Why go into the stats? Well it will all be about the stats once our result set is out, but thats later in P3.





Ok so how does that translate to the observations of PPS....

When we talk cartilage we want smooth operators...slick and not overbearing....somewhat like those smooth lines of a Ferrari:


LESS THIS -





MORE THIS -




In the below figure (Figure D) you are looking at cartilage cells....Normal -v- MPS in the top row....observe the bigger globules of the GAG vessels...they're bloated...that's not good.

Now think of the Bell curve in terms of the second row in the pic below. 1 mg/kg - we don't get much of a result.....I also wouldn't write home about the third pic on the right in the bottom row.....but mate, the one in the middle has the biggest bang for my buck and it's the most efficacious observation out of the dosages as commented by the researchers.I know where my investment dollars should be going...they are going into pic 2 second row...I want my hard earned investment dollars chasing the disappearing bloated GAG storage....



_{Figure D - GAG units like magic, disappearing? How? iPPS.}


When I say you are early to the party...this is what I mean....the average investor does not have a clue about this level of detail...you, are what I like to call, an informed investor.Yes it may not pay off next week...sure in a whole month's time we may not have much difference in our share price...but a longer term hold...2 years....4 years...better yet, 7 years from now....mate I can only guess which of those two cars above I'm going to be window shopping more seriously for.


THE YIN AND THE YAN

I have mentioned in a few previous posts in the past that we have a two sided attack here...NOT only our iPPS works wonders BUT the other alternatives are so bad. A classic area for combatting some symptoms of MPS that some drug companies still are trying to persist with are immunosuppressants. The thing with these immunosuppressants is that they do indeed address some of the symptoms but the side effects in some patients are horrendous. Why? Because they are halting and blocking the immune system. We have seen time and time again that this full blocking of these things that can cause a multitude of problems:


The risk of infection goes up
The risk of cancer goes up

...and the ability of the body to fight other disease goes down

Not a viable solution.



GAGS IN THE URINE

In terms of observing GAGs in the urine the researchers compared normal rats with MPS rats as well as iPPS treated rats at 4, 2 and 1 mg/kg and then compared the oral formulation of PPS.Let's view this as a graph to depict the comparisons in the 6 groups:




The SubQ injections made a huge difference compared with MPS non treated and PPS oral treated groups bringing the result down close to the normal rat readings.




This concludes Part 1.

It's in Part 2 that we will discover some amazing data that involves a part of the body that I did not think possible that iPPS could have a direct effect on....we'll also get to the horse thats of a Trojan variety.