iPPS and the Cytokine

ack to basics tonight....the cytokine.What is this little devil? How does it relate to us....what are the interplays and the interactions? Are they all bad and should be totally stopped? Tonight's Mozz post will attempt to shed some light.



EDITOR'S NOTE

In truth this was always supposed to be just a basic post on what a cytokine is, a time filler as we wait for our IND to be potentially opened? It's a good time to cover this more basic material while we indeed patiently wait for our big day....the potential opening of our IND. Maybe next week? Could slip into the very start of the next week depending on the timing?

Anyway like a few of these kinda posts, I thought it'd be a nice easy straight forward post, catering primarily for the new follower to us...someone that doesnt know too much about what exactly iPPS is, what it can do and in part, how it works it's magic.. It would be nice high level way of introducing the cytokine and just what is the relevance to us.

No way, not that simple. I found more evidence of what your drug can do!

A two parter again tonight with references at the bottom of Part 2.

As usual, please be sure to enjoy.


PART 1


BUT FIRST, A DEFINITION

I'm starting to get the feeling there are really a lot of different proteins in the body...every article I touch....every iPPS related paper I read, it's full of different proteins, different groups and interactions, tonight is no different, another visit to Protein city.

Yep, these cytokines are actually a class of small secreted proteins released by cells. The release of them causes interactions and even communication between cells.

Protein City?

Hmmm ..

Less this:



More this:



The word 'Cytokine' like many of our words in the English language is based on Latin. Two parts, cyto meaning cell and kinos, meaning movement.Yes indeed, put these together and you get cell movement. This is literally one of the main functions of a cytokine, to get a cell moving.

Move a cell to where?

Well, to where the body needs them...it's usually the site of inflammation, infection and/or trauma. In OA, there is plenty of inflammation, usually towards the medium to later stages. So it's the cytokines that are responsible for cell communication and getting things moving. It's the cytokines that are responsible for assisting a cell to utilise chemo physical forces and translate them to mechanical forces that allow them to 'roll forward' ¹ and thus move.

So an important point is that cytokines in themselves are not bad, in fact you need them. It's when they become too much, that's when the problems start. This is the entire motivation of 008, to find the effect our IPPS has on inflammation by tracking these cytokines.


FAST FACT

Jeepers, you think Mozz Quizes ® have crazy large ranges, the estimates for the number of proteins in the body range from 80,000 to 400,000. ^1. Why would they bother with answering that question with such a broad answer/range? Well the rationale is that at any given time there are a different number of proteins and it depends on a lot of factors some of which include age of the organism, diet, weight etc. In fact there are some 250 different kinds of cell types! That all adds up to a lot of permutations and combinations.

Getting too heavy? Are you falling asleep already? Rather than reading paragraphs of Mozz research, how about a pic...love those pics....especially when they aren't to complex!




Let's have a quick look at each:

Macrophages - I love these guys and you should too, they are the ones that are sent out when there is some damage and they literally attack harmful bacteria. Yep they are the troops that are sent when you cut yourself for instance.

Granulocytes - Nope, though they sound like a breakfast cereal, these are actually a type of white blood cell that contains small granules, they also help the body fight bacterial infections.


Fibroblasts - When I hear this one I think of a renovation I once did with a mate. Reminds me of the fibro boards we used to deal with. These guys play a very important role, they are the ones that also help in building stuff...they build the all important extracellular matrix and produce that critical structural framework.


Endothelial cells - Think of this as a layer that's spread out against the blood vessels. It is this important layer that is responsible for providing the medium that regulates exchange between the bloodstream and the surrounding tissues.


Mast Cells - No @Violin1 this has very little to do with our main mast in our pirate ship. But very much like the mast of an olden day sailing ship, it provides an important role within the connective tissues that aid the immune system. Arrgghh.



Now these cytokines are quite dynamic, if the body senses infection or inflammation the large family of cytokines are stimulated and increase in magnitude....a factor of 3 or 4 would be large...but I'm talking an increase in magnitude of almost a thousand fold!

On top of this force, the cytokines have a much larger distributional network at their disposal. Yes I'm drawing future parallels between a vast distributional network we too may have once we partner up....? Nearly all cells that have a nucleus capable of producing IL-1, IL-6 and TNF-Alpha that can be called upon to aid in the manufacturing process.

It is in this way that cytokines have control of localised reactions as well as system (body) wide reactions, yep, as an example, it's a way in which the body will develop a fever if it needs to get the temperature up to combat the nasties in order to fight them.




_{Not a nice place to be...fever...but a necessary evil and one instigated by the proinflammatory cytokines. The increase in temperature (fever) is a defence of the body to slow down and stop viruses that thrive at normal temperature. Increase the temperature a bit and it gets difficult for these viruses to thrive.}



Great lesson in Biology, Mozz Man...but why should I care, how can this be related to my shareholding and the price going UP one day?

Because Dear Paradigmer, this is what you own... Read on just a bit more and it will all fall into place.



THE STORM

Now you will start to understand how this can all go wrong en masse. With such a vast system of cytokines....it really can cascade ...it can overwhelm the body and result in a constant state of inflammation and this is where the body needs a break.

Don't forget OA is a chronic disease...its ongoing...it starts with maybe a little inflammation...but it builds, So too do the cytokines...the message system is itself causing problems...."According to the latest medical knowledge, the participation of the immune system in the development and progression of OA is one of the key elements in the pathogenesis of the disease".² In fact one of the most important effects that these cytokines have involves distinct processes such as catabolism and anabolism processes particularly in tissues that have a higher mechanical load...yes, the joints.



HOW DO YOU STOP A CYTOKINE STORM?


_{What superhero do I need to stop a storm?}


Now the issue is that the answer to this question is not simply to shut off all cytokines and we are done...or even address just one type of these, again, the answer is a downregulation. Some cytokines have an anti-inflammatory role. Shutting these down would exacerbate the problem. Don't forget, we need some of these guys, some of these guys actually are vital...especially in moderation.

Enter iPPS.

The possible solution which will require more research in the future, is to break the incestant loop of a closed illness process. Think of it not as a full block, but as an interruption. Getting these cytokine numbers DOWN...but not OUT. This basic interruption gives the body a chance to catch up. The best analogy is me jogging.

Huh?

I can always do more exercise, I enjoy it when I do some and I get the endorphin rush that a lot of Gym Junkies get. When I go for a jog and I'm nearing the 3/4 mark...if I haven't been for a while it is a good idea to slow down at this 3/4 mark and then walk briskly for a bit, and then pick up the speed again for the last quarter. But, if I have to completely stop at the 3/4 mark...it is terribly hard for me to start again. In the same way, we don't want to completely stop the cytokine storm...we want it to reduce in intensity so the body itself can fight back. It would be too much effort and probably too damaging to stop a storm single handedly...Paul was right when he comments about single targeting drugs have resulted in many failures over time. This is not the way to stop a storm with a single target in sight.


IMMUNOSUPPRESSANTS?

There is drug out there called Anakinra, this acts by BLOCKING the activity of Interleukin. There are side effects, one is the increased chance of TB. Finally it is suppressing of the immune system that results in chances of infections also being increased.

This is why our 008 data will be simply fascinating. Because on one side we know there are very little side effects seen as a result of an injectable PPS formula. We know pain is reduced in the majority of patients and that it lasts, there is durability of more than a few hours or a few days...we are talking months in most cases and I'm not even going to mention my friend @Happell here. He is a (good) unit on his own.


WHAT IS OUR OBJECTIVE?

Well the whole basis of 008 is to show the effect of iPPS on these cytokines. We see a lowering in the inflammatory cytokines and we can surmise that there is a DMOAD effect going on, specially if this is a durable observation. So we must wait ever so patiently. The good thing about this is two points:

1. The 008 trial will not drag on for years and years, we might have the final read out by sometime late next year? Even better than that, we have an interim reading that's slated for Q4 this year or perhaps more realistically Q1 2022? (My views).
2. Put our hand up if you hate waiting. Are YOU the investor that wants results sooner? Well, bad luck.

No actually, I'm just teasing. How about a sneak peak?

Yep...How about a study into a larger animal than a mouse that shows us what the effect of PPS is on some related and relevant cytokines....wouldn't that be a read of interest as we patiently wait for opening of IND and 008 results later on?

Join me in Part 2 for a sneak peek!