he great thing about iPPS is the fact that it acts in different ways. Its not just a single pronged attack...it assists in a number of ways both directly and indirectly.
It doesn't totally block out various proteins such as IL8, IL6 and secreted NGF completely, it downregulates them and that's important to maintain the important physiological functions of the immune systems and other processes..... Yes it is a blood thinner, but a mild one (one 15th that of Heparin)....its safe and its even stable at room temperature....yes, it doesn't need to be stored in a fridge and has a decent shelf life to boot!
But tonight we take on IL8.
What is it? What does it do and just how do we fit into this investigation?
In truth this post was supposed to be a simple post just covering IL8. I discovered a swathe of links and I can no longer limit to just IL8, I can no longer limit it to just one page of a post...
Part 1 will cover some definitions but it wont just be a boring intro, we'll get to some chunkier stuff including some actual results.
Full list of references at the end of Part 2.
Yup, also another bonus tonight...its to do with another IL...I'll include it as a separate section at the end in Part 2 so as to not detract too much from IL8. Don't worry too much if you aren't the science type, I'll make this as readable as possible, do plough through it, there are some very interesting and I believe new facts along the way to keep you interested, to keep us motivated...and to keep us invested!
Please, as always, do enjoy.
PART 1IL WHO ?Before we tackle IL8 specifically, what the heck is an Interluken (IL) anyway?Like a lot of things we cover in Biology related to iPPS, Interleukins are proteins...but they have a set function. These guys are responsible for providing communication between cells. Maybe you can remember them as being the Telstra (
@edski1 and US. guys - think AT & T) for the cells.
Think of Interleukins as the providers/facilitators of communication, less electric cables, more cell protein secretions!In truth, IL's are a subset of cytokines. However, like other cytokines, IL's are not stored within cells but are produced and actually secreted from cells.This secretion is then picked up by target cells via receptors on the target cell's surface. This link...this binding, then initiates a cascade of signals within the target cell which MODIFIES THE CELL's BEHAVIOUR. It's the interleukins that modulate growth, differentiation and activation during the inflammatory response phase. Importantly, a complete blocking of these is
not desirable.
ERRR...SO IL8 IS BAD?Umm yep.
How bad?
Quite bad...
"IL-8 has been implicated in a number of inflammatory diseases, such as CF, ARDS (adult respiratory distress syndrome), COPD (chronic obstructive pulmonary disease), and asthma." Yeah there's more...
IL-8 has demonstrated to inhibit angiogenesis
Has been seen to evoke non-small cell lung carcinoma
Has been associated with ovarian cancer
Studies have shown that IL-8 has prognostic value in many malignant tumours
Can be responsible for melanoma
Promotes the progression of many human cancers including prostate cancer
Has been observed to degranualise neutrophils (important white blood cells)
Yeah pretty bad....
Quote? How about this one as a stunner:
"Aberrantly elevated serum IL-8 level can even precede diagnosis of lung cancer by several years." 1 So the scene is set for the need to bring down the IL-8 levels.
RELEVANCE?Mozz, ....love the science fest...appreciate your efforts to explain away this stuff, how is it related to us? Why should I care? How does this at all increase my outlook on the PAR shares I am holding?
Super question.
YOU should care about bringing DOWN levels of IL8 to even some extent because IL8 can be a biomarker for inflammation and the nasties that go with it as seen above.
Lets have a look at some evidence of PPS specifically on IL8. Yes there is some good evidence so far in Dog models. This was done with the emphasis of MPS however, at the end of the day, its the observation of a reduction of IL-8 that we want.
Ok the pic below shows how well our drug performs within the serum in MPS 1 Dogs.
2 The black column is untreated dogs, the white column is pill format PPS and the grey is iPPS. The dashed horizontal lines marks a dog that has no MPS, ie normal levels of IL8 and TNF-a .
Ok all very good, we know that PPS can have some good results by looking at the blood stream, but Mozz, what about in the brain? When do we get to that stuff, a few years from now? Could iPPS really have much of an effect on the markers in the brain, there is of course the ol' BBB to contend with right?
(BBB = Blood Brain barrier that disallows large molecules from entering).
How about it is has already been observed!?
What?
Here is a pic of
where I'm talking about and once you see this pic
2a, you'll get an understanding of just how important this stuff is, this is
one area you really wanna avoid inflammation if you can!
So what's all this about ALREADY having witnesses some results here? We will get to that in just a sec.
Guess what time it is?
Yes you are correct, Mozz Quiz® time.
QUESTION - What percentage reduction would be a good outcome in the dog's CSF brought on about iPPS's action?
ANSWER
A) Well it wouldn't be too much...maybe around 20% as a realistic option?
B) Nah its always more than you think yes I know that we are talking the crossing of the Great Divide (BBB)...lets go a full 30%.
C) 50% ??
Let me show you the graph and that will tell you the %.
Results from within the Canine Cerebrospinal fluid
7:
Black - No treatment
White - Pill format PPS
Grey - SubQ, iPPS...The wonder drug.
Mate, that's what I call a fascinating reduction, the two asterisks (**) represent a P value of < 0.005.
If you take only
one point away from this entire post...it is that iPPS has a dramatic effect on IL8 levels potentially in the brain. This will be investigated much more in the future.,..keep this ace with you, my views only.
Here is what the researchers had to say (CNS = Central Nervous System):
"These results confirmed previous studies in MPS VI rats showing reduction of several serum inflammatory cytokines, and reveal for the first time the potential of PPS to influence CNS manifestations."Paradigmers...these are the bread crumbs I'm picking up in the forest on the pathway to that house of candy one day. Not saying its soon and not saying its a simple journey...I am saying its a lot of potential candy we may one day discover.
ANY ONE ELSE WE NEED TO KNOW ABOUT?For a company to do well, they can't have too much competition, they need a free run, a window of opportunity. In our case, I personally believe we are going to get a good long window, a good long run. There is very little a Doc can prescribe once OA has really progressed. Surgery ends up being really the only thing one can eventually do when its all too much. But, as a fellow poster reminded me the other day, when you have serious inflammatory conditions of the brain, how can you do surgery of certain parts of the brain?
What is commonly prescribed for inflammatory conditions of the brain to try and abate these IL8 levels??
Yes there are other drugs that can bring down the level of IL8, examples include ibuprofen and dexamethasone.
If you have read my posts in the past you are cognisant of what ibuprofen is, a NSAID. We know that NSAID's have a raft of side effects and can actually lead to further joint problems.
Relatively new to Mozz? Read this post on NSAIDS (Single left click the hyperlink) ----->
NSAID's Dexamethasone is a class of corticosteroid. It actually reduces inflammation to a good extent BUT, there are also a number of side effects and some are serious. So much so that it is advisable not to use it for prolonged periods. There are that many potential unwanted effects that I have run out of Skull and Cross bones to list them all, you'll find them in the Appendix A of this post at the end of Part 2.
Go back to that last chart above...work out the drop in IL8 that was observed...that's something in the order of
90% !?! Now I have a number of caveats here, this was witnessed in a study of canines, its just a small sample size...so do take that into consideration. But this IS peer reviewed, here is the link:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4827827/The other point here is that the researchers at this very early stage are saying that there are many benefits of getting on to iPPS earlier rather than later specially in the MPS indication. I can no doubt seeing this being rolled out early to any child being diagnosed with MPS one day. I, for one, will be researching and pushing to gain more info in this area. There are real incentives for such safe drugs that can change lives, particularly that of children.
This concludes PART 1.
Its in Part 2 where will we cover this Dexamethasone drug a bit more, we will then turn to more results of our iPPS specifically in the brain.
Watch out for an all new bit of information that will surprise you in terms of a certain condition we may one day be able to address.
(20min delay)