We now have an idea of what HA is, what are some of the vital functions it serves....now lets get a better sense of the HOW and learn more about the HA molecule itself. I'll also whip out my CT scanner for an in-depth look at just one of the points/functions mentioned in Part 1... But first, do we need to be concerned with anyone by-passing iPPS?
WAIT MOZZ.....CAN iPPS BE BY-PASSED? - SHOULD I NOW BE WORRIED?
Ok so we know that HA is important, why then cant a patient that is suffering joint problems and perhaps can't wait like us longer term holders. Why cant they inject synthesised or animal derived HA directly into their joints?
Well there are a number of points here to address this:
HA direct treatment involves a direct injection into the knee/joint, that's not for everyone, there can be some pain, there can be a chance of infection, and it doesn't work for everyone. Ok Mozz, how many people does it work for? Or not work for?
About 30 - 40% of HA direct injections don't work.
You can't use HA injections if you have had cancer.
HA works better in patients that have only mild to medium levels of OA and they tend to not work as well for people that are obese and for people that have advanced OA.
Possibly the best point for us, or more importantly, why direct HA treatment isn't comparable to iPPS? "...they [HA injections] can’t change the underlying cause of your osteoarthritis ". 6
Paradigmers, it is that last point above that does it for me. I'm not saying that we will regress every OA case, certainly not...but we regress just 5%...we slow the disease down in just 10%..mate that will be outstanding. No other drug to date has been proven to be able to do this safely, effectively and for any decent amount of time. No wonder our valuation in terms of pricing potentially could jump from $2500 to $6000 plus one day. Do the maths...the uptake one day could be quite incredible....specially if we become first line treatment.
THE HOW - THE NOTES
Ok so now we know that injecting HA directly into the joint might have some merits but it doesn't stack up...lets cover off the HOW...How does iPPS work on HA?
Remember The note from part 1? Here is a refresher from Part 1:
Note 1 -Mate, as an example lets chain this out...remember, this is my speculation here...so take that into consideration: lets get a better sense of the HOW.
iPPS helps stimulate production of HA in two ways - Increased volume and production of higher weighted HA (We'll cover this in more detail later in this post). This in turn allows for adequate and increased growth of the very very fine vascular framework which is acutely required close to the bone and cartilage. This now facilitates increased supply of nutrients to the cellular structures and is responsible to not only to stop the rot...but I'm talking HEALING...and potentially at least some regression of the disease (subject to further testing)...in some cases I'm talking GROWTH.
So taking this stimulation of increased vascular network a bit further, lets take a look at what this means...Here's a pic:
So what are we looking at here? 12
(a) This is a schematic diagram of the vessels in a given bone. (b) This is an actual photograph of a view from a microscope of a blood vessel right up into the bone. (c) Section view cutting through the bone (d) CT scan of a mouse tibia depicting the blood vessels using a contrasting agent (e) A 3D rendered image of the blood vessel network. This is the stuff iPPS can directly and indirectly influence via the production of HA (subject to further research/trial).
Perhaps again, not directly, but certainly indirectly by tipping the sea saw back in the body's favour. No longer the body is too busy being on the defence...it can now be on the offence. In other Mozz words...it assists in the body getting away from simply fighting the CONSTANT state of inflammation, the cascading of the never ending cytokines.... it gives the body a chance to start repairing...and start constructing.
If you have a flood that never subsides, that never abates, how the heck can you pour new concrete for new foundations and start building a dry new wooden framework on top of it?
Break this cycle....
Paradigmers, this is just one of the many facets where iPPS plays a role, a role that is seldom advertised or publicised. You wont see these images in the Herald Sun...when that Barefoot guy (nothing against him, I actually like his work) starts writing about PAR, it's entirely too late (my views)....its time to wade into the future pool of investing NOW (not advice). Again in just my views, it is this research that not many tend to do that points out what our potential MAY be one day in the future.
LOW -V- HIGH WEIGHT HA
First a little background, our own wonder star molecule is estimated to be around 5000 Dalton...what is a Dalton, well not very much, I know there are a few amongst us that will know how much (how little?) 1.66 x 10 -24 actually is...(isn't!)...it's very very light. So HA molecules can weigh between (light) 4,000 to (heavy) 8 million Dalton....it gives you at least some comparison....
Ok thanks for the science measurement lesson Mozz, tell me what is this light and heavy weighted HA used for? Is one better than the other?Well its more of the benefits that each one offers....like much in life, everything has a trade off....
Yeah the heavier weighted HA doesn't last as long as its light weighted brethren but it has benefits such as being higher anti inflammatory than the lighter weighted HA. Important for us....its the HW HA that iPPS tends to stimulate production of the most. The bio mechanics of HA vary completely depending on its molecular weight.
Lets now break down these HA MW properties.10
Hyaluronic acid with molecular weights from 0.4 to 4.0 kDa acts as an inducer of heat shock proteins, and has a non-apoptotic property.
Polysaccharides with a molecular weight equal to 6–20 kDa possess immunostimulatory, angiogenic, and phlogotic activities.
Hyaluronic acid with a molecular weight of 20–200 kDa takes part in biological processes such as embryonic development, wound healing and ovulation.
By contrast, high molecular weight hyaluronic acid (>500 kDa) has anti-angiogenic activity, and can function as a space filler and a natural immunologic depressant.
In addition, it has been observed that higher weighted HA can lead to cytoprotection, ie staving off harmful toxins to cells.
"The Molecular Weight of HA appears to play a critical role in the formulation of the products used in the treatment of diseases". 7
Further, lining up with our ongoing 008 program, this statement from another peer reviewed paper:
"Synovial fluid lipid transport and inflammatory proteins are significantly decreased after HMW HA injections". 7.5
...and another quote from a different study:
"HA of high molecular size, usually in excess of 1,000 kDa, is present in intact tissues and is antiangiogenic and immunosuppressive, whereas smaller polymers of HA are distress signals and potent inducers of inflammation and angiogenesis".2
This is the power of YOUR iPPS.
THE GOOD OIL
Ok so I think of HA fluid as an oil. A car cant function without fuel...but it can function with less or defective oil. HOWEVER, long term damage of the engine will result if you have inferior or not enough oil. Oil is vital. I liken this to HA. Particularly in the case of OA....we know that iPPS is at least somewhat responsible for the increased production of HA. HOWEVER, oils vary in quality. Its not just volume we are after dear reader. We want quality. As we get older there is less higher weighted molecular HA....this could be another link to OA...iPPS will at least give us a few more years back potentially. Now that's worth something.
Penny hasn't dropped yet? Ok let me Mozzify ® it....what drug do we have? iPPS...sure....what is Pentosan? It comprises of Pentose...Pentose is a sugar.
You have heard of fighting fire with fire right? This is fight sugar with sugar. Except we aren't fighting...we are eliciting...we are encouraging...we are causing good reactions...we are resulting in repair...
1985 Castrol Ad...love it....and remember, "...its worth a few extra cents"....in our case, dollars....if you guarantee me longer lasting engine (joints?), natural based lubricant, multi methods of performance....right viscosity....consistent product, non addictive AND SAFE....it's an oil I'm going to be darned happy to pay more for.
iPPS has been found to stimulate the higher molecular weighted versions of HA, . It is THIS HA that is part of the potential magic.
One final piece of evidence in terms of PPS's stimulation of HA 8:
Again we know iPPS is safe...but how does it compare to direct HA injections? 8
"... the incidence of local- and treatment-related AE vary from l% to 8%. As pentosan is a subcutaneous injection administered far outside the joint, while hyaluronic acid requires intraarticular injection, pentosan is considerably safer in this respect. Furthermore, there are only very rare incidences of pentosan AE according to the complete reference for the Summary of Product Characteristics of Pentosan polysulfate SP 54. Treatment with pentosan seems to be considerably safer. "
IN CONCLUDING...
So we know HA is vital,. Broadly we saw there are three main important functions HA plays:
Lubrication
Growth of Cartilage and Bones
Reduction of Inflammation
We know it has many incredible uses in the body, we also have discovered just how prevalent it is in the synovium and this has strong ramifications in terms of OA. There is proof that as you age the MW of HA decreases. Conversely we know that iPPS plays a pivotal role not only in any old HA formulation but particularly the Higher Weighted HA.
We know the safety profile of iPPS. Yes there are ways to directly inject HA fluid straight into a joint, but this comes at a cost, its higher risk and finally, in my books, there is nothing quite like the natural stimulation of this gel like substance from within our own bodies.
It reminds me of an ol pal that used to say to me on occasion when we'd have a top hand in our team playing cards (500 - An Aussie card game) when we were in Uni...with a cheesy grin she'd proclaim joyfully "Mozz, we are sitting pretty".
We just may need to sit a bit longer, yeah?
Finally I also kinda agree with 'Sol' from the old Castrol GTX ad days on this one....
HA direct treatment involves a direct injection into the knee/joint, that's not for everyone, there can be some pain, there can be a chance of infection, and it doesn't work for everyone. Ok Mozz, how many people does it work for? Or not work for?
You can't use HA injections if you have had cancer.
HA works better in patients that have only mild to medium levels of OA and they tend to not work as well for people that are obese and for people that have advanced OA.
Possibly the best point for us, or more importantly, why direct HA treatment isn't comparable to iPPS? "...they [HA injections] can’t change the underlying cause of your osteoarthritis ". 6
(20min delay)