iPPS and Inflammation

ometimes its just good to get back to basics.



Tonight I cover Inflammation. What is it, how it manifests itself and what Injectable Pentosan can do to address it.






Think of inflammation as the body's response to injury, but these injuries can also be 'insults' such as microbial, autoimmune and metabolic.


Typically, but not always, inflammation results in these physical symptoms:


Redness
Heat
Swelling
Pain
Loss of Function


We usually see all of these signs in the main focus of our drug, ie Knee OA.








Does this mean we need to completely block out all inflammation and pain?

Well the answer is a resounding NO.

We still need some inflammation as inflammation actually triggers the body into action mode.A bit like those fire fighters that have been conditioned to automatically respond after many cycles of training when they hear the audible Whoop Whoop and see the flashing red at the firestation, its action stations, they don't even have to think of what steps to take, they are conditioned. Its the same for the body...




_{Action stations...when those chemical secretions go off..it's action time...not unlike firefighters when the alarms and flashing trigger.}


The Macrophanges are activated, the white blood cells are called to action. When an ambulance or a fire engine comes screaming down the road what does the law state, you must give way to it, you must slow to 40 km/h (Law in most of Australia)...you must give a wide birth to it. Paradigmers, our body's are the same.




Did you know the body increases blood flow to the area, two hormones known as bradykinin and histamine are responsible for causing the small blood vessels in the tissues to dilate (become wider). This then paves the way for a bigger road to allow the blood to access this region. ...The swelling is the expansion of the road...this allows the ambulances and fire trucks, the increased macrophages and immune cells, to be delivered to the site of injury.

But that's not all, there are many processes that are triggered on the inflammation alert; the same two hormones deliberately irritate the nerves and you and I know what that does, it causes pain. If the inflammation hurts, what do you naturally do? You protect that area!

But is Inflammation always a good thing?

While Inflammation sets off vital processes that are required to succinctly address the underlying condition, inflammation can cycle...a bit like a bung (Aussie slang meaning "to no longer work") dishwasher that sometimes gets stuck...over and over again she goes....its counterproductive...we don't want this - the immune system sometimes fights against the body's own cells by mistake.





_{Help, my inflammation dishwasher is stuck!}


We need a circuit breaker...it's here where we need Pentosan to break this cycle. However, unlike other drugs that just switch off the power and the dishwasher is rendered useless...we want to slow it down, and remove the blockage without stopping the vital processes of the body.

Downregulation is key.


But we know the real magic is the fact that Pentosan isn't uni-directional, it has a number of you beaut-mechansims.






...Yeah it's bad....


"When it’s good, it fights off foreign invaders, heals injuries and mops up debris. But when it’s bad, inflammation ignites a long list of disorders: arthritis, asthma, atherosclerosis, blindness, cancer, diabetes and, quite possibly, autism and mental illness". ¹



When inflammation is bad it can indeed cause havoc, but it can also kill. Is there any wonder why OA which is highly inflammatory has been defined by the FDA as a Serious Unmet disease.

Paradigmers, our story is starting with OA...its starting with MPS but you know what? I get the distinct feeling it just isn't going to end there. Obesity and Type 2 Diabetes are rampant across the world, the growth rates of these two diseases are off the charts.


Break time, crack open the red^* please....what time is it? (* = Drink in moderation)


It's Mozz Quiz break time of course...




QUESTION - Obesity from the period of 1999 - 2000 through to 2017 - 2018, just a 7 years difference, what was the increase in US obesity prevalence as a % between those two time periods?


A) Something around the CPI, 2% ?


B) No, I'm a smarter guesser, its always more than A) ... Let's double 4% ?


C) Gosh darn it, this is a Mozz Quiz ^®.....Multiples of Answer A)....hmmm....11% ?




Yeah again you were pretty close with your guesses.......




The answer is a 39% increase.

The rates went from 30.5% to a massive 42.4% ! That's a 39% increase in just seven years?! ³

Diabetes type 2 is growing at 6.1% per year. ⁴

Hold up Mozz mate, you are going off a tangent, we are talking about Inflammation here mate...why are you bringing up Diabetes and Obesity?


Ah yes, how remiss of me to get side-tracked so easily..... NOT !

Here is the link:


"Obesity and its constant companion, type 2 diabetes, are at epidemic proportions in this country. One thing that connects them is inflammation". ¹


Yes, read that statement again..there is a connection between Obesity, type two diabetes and inflammation.

The first responders (remember the ambulances) are macrophages and white blood cells, they produce waves of cytokines which are primarily good, they kill germs...they sound the alarm for mass production of inflammatory cells...BUT fat cells can also produce cytokines and as fat tissue grows....well they attract inflammatory cells...if this gets out of balance...it cycles to the determent of the body.

How is it linked to diabetes?


"Inflammation also antagonizes the action of insulin, the hormone that stimulates muscle and liver to absorb glucose from the blood. And obesity, insulin resistance and type 2 diabetes, in turn, increase the risk for heart disease".


Ahh and now we also see the damage to the heart. Again we already know there is efficacy of Pentosan here too...in the heart. Much more to be studied? You bet. We have just completed our first pre clinical heart failure model, I have much more to be said on this topic alone...but that is further down the list.

These quieter times in our share price gives me a chance to research and write. When our share price eventually goes from strength to strength and PAR are churning out the announcements, mate I will be just too happy and excited to research...my eyes will be glued to the screen!






A biomarker I haven't mentioned specially before. Though it does fall into the indirect biomarkers I have mentioned. What I mean by that is remember the graphic equaliser post I did?

(See Part three in this series: https://hotcopper.com.au/threads/008-further-explored-and-a-bonus-kicker.6370213/?post_id=57024835)






I mentioned in the 008 post (see link above) that most biomarkers we want to see come down...but not all of them. IL 10 is one such biomarker, we actually want to see this one go UP!

IL-10 is an anti-inflammatory cytokine. The action of iPPS is to increase IL-10. Obesity is a culprit that tilts the delicate balance in favour of inflammatory cytokines. So again, we see iPPS working in multiple ways...it helps binding...it helps to thin the blood just enough..it helps to increase the thin vascular network...it assists in downregulating NGF and the inflammatory cytokines BUT it also assists in increasing such required cytokines as IL-10.

The action of iPPS was also seen in our own pre clinical model, namely RRV:

"PPS treatment resulted in an early surge of IL-10 in RRV-infected mice, with significant elevation both at day 1 and day 3. (P < 0.001 and 0.01, respectively)". ⁶




How does this look on a chart? ⁶



Nice P levels there...





So what's the alternative?

Well currently if your knee is hurting, your elbow is in pain or perhaps your lower back has OA...its really only pain killers. Yes early on they will recommend shedding some kilos, exercising and the like, most people don't end up doing the necessary exercise and diet change required to be sustained over not just the first few weeks after consulting with a Doc, you need to do it ongoing. Eventually it becomes too painful and stronger medication is required and eventually rectification surgery or complete joint replacement is on the cards.

Apologies in advance...I'm a dad, dad humour escapes me on occasion....again, you have been warned:




_{Get it? - Join replacement eventually on the cards.... Yes ok I'll stick to my day job then.}






The anticipated market penetration, if our drug data is good, is ONE side of the equation, the other side is how good the current std of care is.


"...prolonged therapy with anti-inflammatory and cortico steroid drugs, which have been the treatments of choice for arthritis and other disorders for many decades now, can lead to the breakdown and failure of connective tissues, particularly joint cartilage". ⁷



I could do an entire post on the dangers but here is another quote:



"Except for aspirin, all over-the-counter NSAIDs now must carry a warning about the risks of heart attack and stroke along with other side effects.NSAIDs have other dangers, too. They can cause high blood pressure and kidney damage in some people. They can also cause potentially severe allergic reactions. Both prescription and over-the-counter NSAIDs now carry warnings about skin reactions as well". ⁸


Yep, both sides of the market potential for us are pointing to something big.







Inflammation is everywhere, not all of it is bad. We actually need some to keep us in check, to warn us, for us to address it and the underlying problem. Chronic inflammation is another matter. The body needs a chance to be able to put out this fire, literally. iPPS is now being thoroughly tested in numbers in our P3, the results once out will no doubt, in my opinion, cause large waves in the industry.

Certainly its one thing to address inflammation and down regulate it to restore the balance, its quite another to do that SAFELY.

I can't offer any advice here, I'm not licenced - I have no ulterior motive, I do not directly gain if you buy or sell..it's up to you. I present what I see.
I'm indeed a long term holder and as long as the err...paradigm doesn't change....I intend to have more than a handful of shares when we get big ...


Really big.

MAIN REFERENCE

1] https://medschool.vanderbilt.edu/vanderbilt-medicine/the-good-the-bad-and-the-ugly-of-inflammation/#:~:text=When%20it's%20good%2C%20it%20fights,possibly%2C%20autism%20and%20mental%20illness.


OTHER REFERENCES

2]https://www.ncbi.nlm.nih.gov/books/NBK279298/#:~:text=When%20a%20wound%20swells%20up,a%20splinter%20in%20your%20finger.

3]https://www.cdc.gov/obesity/data/adult.html#:~:text=From%201999%20%E2%80%932000%20through%202017,and%20certain%20types%20of%20cancer.

4]https://dmsjournal.biomedcentral.com/articles/10.1186/s13098-016-0186-9#:~:text=The%20prevalence%20of%20type%202%20diabetes%20increased%20by%20an%20average,diabetes%20at%20a%20population%20level.

5]https://www.healthline.com/health/type-2-diabetes/statistics#Prevalence-

6]https://journals.asm.org/doi/full/10.1128/JVI.00224-15

7]https://www.naturalmedicine.net.nz/wp-content/uploads/2013/10/1-Polisulfate-to-PDF1.pdf

8]https://www.webmd.com/osteoarthritis/features/are-nsaids-safe-for-you#:~:text=Except%20for%20aspirin%2C%20all%20over,cause%20potentially%20severe%20allergic%20reactions.