The PhD - NO and the DMOAD magic of iPPS... PART 1
ecently I came across some more research involving our Magic Juice...It's a very involved and in depth report from Japan. Tonight I break this report down somewhat. This paper attracted me because of two reasons:
1) It is a pHD discourse that has the word DMOAD in it's title.
2) It was conducted by a contending Doctor from the university of Hokkaido. Why is this special? Because that's located in a city called Sapporo and I do like the beer that has the same title..(specially in the can, bottle is ok, but the cans are great!).
Cheers! Great beer, from the same place as the guy I'm basing this post off!
In truth to really do justice to this PhD paper, I would need to break it into multiple parts, so comprehensive it is. But I while I do my best to Mozzify ® it (simplify it) I endeavour to limit this across just two parts. Those of you that are super keen to thoroughly investigate, do at least flick through the Japanese paper, duly linked in Reference 1 (see Part 2 for references). This will be a long post, so again, I implore you to get comfy, take your time to read this as there is a fair bit in it and I will try not to make it too heavy (yes for your benefit but more so for MINE!).
A sciency warning for sure, perhaps quite timely in light of our upcoming inaugural R&D Day. I understand this can get a little boring for some but if you can tough it out and endure it, I think you will enjoy it all the same. As with any research any of us provide, please do your own checking, I'm not a scientist, I don't often wear a white lab coat and those science glasses (though I have mowed my lawn with those on in the past, only the backyard), I'm just interpreting the info as I see it and simplifying it as I come across it for our benefit . In doing so there could be errors. Always best to...well you know, DYOR.
PROLOGUE
Paradigmers, I cannot sit still when it comes to PAR. I thirst for more....I know there are periods of time when nothing happens, nothing is visible, there are no announcements...there doesn't seem to be much happening...but you know what, LOTS is happening. We have much on the radar. The folks at PAR HQ are busy, very busy...they are not idle....to this day Im impressed with the staff, as I said I was disappointed last year at the AGM I didn't make it to all of them...I could very easily have 30 min conversations with each and every one of them....to ask them of their story, to ask them how excited they are...to learn more about their role...
When I have a vested interest I am curious to know how it works. I have given the car analogy many times before....it is NOT enough for me to hear the footballers and the average citizens say that they feel better. I WANT THE HOW....I want the WHY. I really do not care how much science jargon they throw at me, I will take each word at a time and disseminate and extract the meaning . When I am an informed investor....I am in a different and much higher position. I can plan...I can de-risk it in my mind and granted things can still go wrong (and get delayed *wince*)...but I'm at a different level of awareness.
PAR brethren, I strive to keep your momentum going. I want you to hold long term (not advice)...yes I understand it is boring...it is a long term play and perhaps a little longer than we initially expected...Don't give up....there can be both negative and positive surprises and OA though it is a long slog, it isn't the only thing we are tackling and in my express opinion, we should be able to garner revenue from MPS/TGA etc. before the P3 OA trial is done.
I really do believe that if you can just wait it out...and I'm not unfortunately talking months here...I am really talking years...at least four years. Five is better...whatever you can keep will in my express views, will be valuable. Not unlike APT...going form $7 to $100...not unlike MRNA..going from $26 (when it first came on Mozz's radar it was $26....to $152 USD at the time of me writing this.. and that was just 8 months ago! Yes I missed APT really...(does 55 shares count? That all that I have left *pout*). I made a little on MRNA...
PAR I will not miss...and neither should you. I'm not saying to go nuts and back up the truck, I am saying to get a meaningful exposure without being silly and WITH you still being able to sleep each and every night...what does that mean? I mean that if a disaster were to happen you could survive and you don't need to ever pass the hat around.
INTRODUCTION
The PhD presents a very good summation for OA and the associated workings of the disease. The emphasis is on dogs for this particular paper. There are a couple of good papers out there, this is one of them.Ok curious about the subject of this post? Yes we will get to what the random "NO" means...
In case there are any new guys to us..DMOAD stands for Disease Modifying Osteoarthritis Drug, and nope, there to date, is no such thing.For the first time I came across the prevalence percentage of OA in dogs...if you met me down the street and randomly asked me what % of dogs suffer OA I would've guessed 10%...The paper reports it as some 20% of dogs after just 1 year of age. It further gives us an insight on OA in horses suggesting the incidence is pegged at around 13.9%.
In Humans? Well we know some 3 million officially Aussies have it...Australia's' population is now 25 mil...getting out my trusty calc (I have bought one that can handle TENS of Billions specifically to cater for PAR's potential long term revenue (my views - oh hush legal dept)) that computes to be 3/25 = 12%. Hmm Mother nature is consistent isn't she?
None of these mere 8 digit calcs - 12 Digit required tool at Mozz HQ's...one day I will use this device to calculate our revenue...do not laugh, $100 a share IS possible!
In the intro the PhD paper depicts OA as a "primary disease of joint cartilage" but the incidence of abnormal stresses on the joints also plays a significant part in the incidence. The Intro further goes on to succiecnelty state that the disease "not only affects articular cartilage but also involves the entire joint including the subchondral bone, ligaments, capsule, synovial membrane and menisci although a common feature in all OA and related disorders is loss of articular cartilage in association with bone features such as osteophyte and subchondral bone sclerosis". Yes as Paul Rennie just recently mentioned at the AGM and Evercore presentation, this is not a one symptom and not a one factor disease. There is much at play here and it required a multi faceted approach. A drug targeting a specific biomarker has not to date proven successful. We need a more broad based acting agent to go up against the carnage that OA inflicts.
Mozz, I get the Japanese Study part ...and the DMOAD aspect...but what's all this about "NO", was that a typo?Yes sorry for the confusion, I'll get to "NO" and what exactly this means soon and how I'm not necessarily losing the plot...
WORKINGS of iPPS
Ok so we know iPPS acts on multiple fronts in multiple ways...but one of the beaut things it brings to the table is the fact that it buys time for the articular cartilage to self-renew and repair itself. Current remedies only attempt to alleviate discomfort, merely and feebly attempting to tricking the body to quash some pain. The body is smart and automatically compensates by growing extra sensors to further detect pain and alert itself into action. No wonder the current of std simply works less effectively over time.
What is the point of putting a band aid over a bullet wound.....you ain't treating it..you aren't promoting healing. "However, these interventions do not alter the underlying pathophysiological process on the structural degradation of joint tissue". IPPS increases blood flow...it addresses pain via NGF...it allows for more nutrients...white blood cells...macrophages and a whole heap of other aids to be involved and delivered directly to where it is needed. It is here where more data..more analysis and research will be conducted and peer reviewed so we have an even better understanding of how these workings are at play.
So in Mozz words there are three levels we need to act on:
1) STYMIE further destruction 2) ALLOW for the body to heal itself 3) PROMOTE and ENCOURAGE the regneuivnation process with an 'active' but fundamentally natural drug.
A true DMOAD takes on all three...this is not just a band aid...this has the potential to stop AND possibly to reverse the disease. A separate trial to investigate this DMOAD property is inevitable...let me tell you here and now,..that trial, if it shows officially even a small % of DMOAD ability, it will be another world for us.
Violin1? Pirate Day 2027 we actually might just hire out a cruiser, a fit Pirate Ship indeed.
BALANCE
The paper then goes on to importantly state exactly how I have viewed the DMOAD properties of our Magic Juice...the allowing for the body's regeneration process to be encouraged to work ...this is articulated well in the following paragraph that is a citation from another source:"Cartilage tissue degeneration leading to OA occurs when the equilibrium between breakdown and repair of the joint tissues becomes unbalanced (Alcaraz et al., 2010)".2
Paradigmers...it is the equilibrium, this balance that is allowed to work as a direct consequence of the action of iPPS...It gives the body a chance to repair...to rebuild...there is nothing on the market like this....and whose mode of action is fundamentally safe (subject to P3, my views).The imbalance, as the article goes on to describe is the "cytokine cascades and the production of inflammatory mediators". It is iPPS that can handle the inflammation and is charged with the responsibility of reduction of the same in a safe fashion.
CYTOKINES
I always assumed cytokines are some sort of biological production ...kinda like a swarm of bees...released for some purpose.
Mate, something out of a sci-fi movie perhaps, can you believe this stuff is inside us?
I didn't realise there are a few sub classifications, some of which include Interleukins, Lymphokines, Monokines, Interferons.4 The challenge for PAR next year is to get through a good chunk of the phase 3......the challenge for me next year, it to come up with some meaningful interpretation of all of these cytokines and what it all means and Mozzify it. (Dumb-it-down)These all linked to the pathogenesis of OA.
RISK FACTORS
The paper then goes on to state the increased risk factors for OA:
1) Age 2) Joint trauma 3) Altered bio mechanics 4) Obesity
The paper states that after a period of degeneration, it becomes self-perpetuating. I have stated this fact much earlier on n a HC post, some 50% of sporting injuries lead to OA after 10 years. The Japanese paper states it in this way"In some cases, the initial process may be a mild injury to a collateral ligament and these tend to recover fully, but the associated cartilage damage results in clinical disease of the joint years later."
It is the joint degenerating over time possibly due to the inflammatory process. This is just one way iPPS addresses and halts this destruction.
LET'S ADDRESS THIS PROPERLY
The so called current standard of care whether it be Opioids or NSAIDS or even Corticosteroids, merely focus on pain relief and the paper states "these interventions do not alter the underlying pathophysiological process on the structural degradation of joint tissue but merely control signs of pain and inflammation". Yes they control pain...yes they have some effect on inflammation but they result in problems.
My interpretation of the problems are:
1) The pain relief is limited (hardly 15%) 2) They have nasty side effects....one of them (eg corticosteroids) is the further destruction of Cartilage! 3) They can be addictive (eg Opioids). 4) They are band-aid treatments and do NOT address the underlying issues.
We want and have a solution that can assist in the altering of the underlying pathophysiological processes.The paper does refer to the study conducted by Dr Ghosh along with Sunaga et al. 5 who was one of the research papers mentioned by Paul in the last NWR seminar in regards to a mouse model study..The paper then points to a study conducted to investigate the action of PPS on various cytokines and the conclusion was that the "protein expression was significantly abrogated by PPS" and further "The findings of this study demonstrated for the first time that PPS is a novel inhibitor of IL-1-induced iNOS, c-Jun, and HIF-1α mRNA up regulation and iNOS protein induction which may be beneficial for prevention and treatment OA."
One of the tell tail signs of OA is the presence of a gas known as Nitrus Oxide (NO). This is a gas produced by the enzymes that break the cartilage down.OK so the PhD paper then goes on to investigate the effects of PPS and evaluate its chondro inductive potential to restore and promote chondrogenesis of cBMSCs . WHO? Mozz you lost me. Mozz Speak? Simply, they wanted to investigate PPS's ability to to repair cartilage tissue and repair of OA related cartilage lesions. Yep. the whole DMOAD concept.
Now don't forget, to date, out there in the market...out there in the known world, there is nothing to date that has this property.
SO NO, IS GOOD?
HOLD ON MOZZ...NO IS GOOD!Well yes, NO in itself is good...but guess what? Too much NO, like a lot of things in life...is BAD...I mean real bad...How bad?Let me tell you.
Ok great Mozz, gotta hand it to you...I understand that NO is a gas, we need some, but too much is bad...but what does it have to do with me PAR shares?Ah well Paradigmers, here is the connection:"Of particular interest, OA chondrocytes express inducible nitric oxide synthase (iNOS) which in turn produces high concentrations of NO, especially upon stimulation by pro inflammatory cytokines". Yes you read that right, we have another bio marker in our midst. Quote time.....again from the paper: "Importantly, the elevation of NO production appears to be an important factor in the pathophysiology of OA iPPS the Inflammatory Buster."
The paper suggests that initially you might have a relatively small injury for example, but over time if not addressed this can lead to ongoing inflammation and this is where it becomes potentially serious and OA sets in, the joint degenerates due "continuing insult from the inflammatory process". In chorus with Paul the paper states clearly "OA should therefore, not be thought of as a single disease, but rather as the clinical endpoint of numerous disorders leading to the eventual failure of one or more joints of the body". Paul and even Donna both deliberately highlighted this multifactorial nature of the disease and gave us clear examples of recent failures (GLP 1972) that attempted to address just one biomarker, one part of the disease and failed. Our war-game is so different, we fire a missile with multi war heads....we already have seen the evidence of just how well it works and the FDA and EMA will soon be witness to these workings for themselves. (My opinions).
STUDIES AND RESULTS
Ok so this PhD paper refers to the same researcher Paul mentioned in the AGM, namely Sunaga et al. from back in 2012 and of course Dr Ghosh's work. I enjoyed reading how this papers expresses the findings:"PPS has been shown to be involved in prevention of inflammatory intracellular responses...and preservation of cartilage integrity by supporting chondrocyte anabolic activities, including biosynthesis of aggrecan and suppression of catabolic MMPs". Why don't we Mozzify this a little. What they have found in the past is that PPS helps in the production of aggrecan. What is this? Its basically a hydrated gel structure7, vital in load bearing joints.
At the same time, a bit like the Yin and Yang in that it promotes the positive activity and ALSO suppresses the negative, it had a hand in the suppression of catabolic MMP's. MMP's are basically enzymes that are responsible in assisting wound repairs, quite important where there is cartilage destruction at play. Ok so the focus for the PhD paper was trying to determine if there is any merit of PPS as a DMOAD and the production of NO was a central phenotype that was looked into.
STUDY 1
In the first study this paper covered, the purpose of the experiment was to take three dogs and to "investigate the inhibitory effects of pentosan polysulfate (PPS) on IL-1β-induced iNOS, c-Jun and hypoxia inducible factor-alpha (HIF-α) isoforms upregulation in canine articular chondrocytes".*whew* a sciencey way of saying they wanted to research and investigate IF iPPS can prevent and at least reduce this NO production which we know too much of is a result of OA processes.
What was done? Chondrocytes were isolated and cultured from femoral head cartilages of three dogs. They then used varying levels of iPPS, namely 0, 1, 5, 15 and 40 μg/mL of PPS .Yes Paradigmers, effectively a kinda dosing regime that PAR will also go through perhaps with different amounts in the dosing study set to commence sometime next year.
Great Mozz...take me to the results.Sure...listen to this and I will quote from the paper itself as I just can't do justice and attempt to express it in Mozz words....:"The findings of this study demonstrated for the first time that PPS is a novel inhibitor of IL-1-induced iNOS, c-Jun, and HIF-1α mRNA upregulation and iNOS protein induction which may be beneficial for prevention and treatment OA."
"As consistently observed, a combination of rcIL-1β + rcTNF-α + LPS significantly induced iNOS protein expression but pre incubation of chondrocytes with PPS significantly abrogated iNOS protein induction hence proving the inhibitory effects of PPS on both iNOS mRNA and protein expression."
Paradigmers....fundamentally this stuff works...another biomarker like COMP...like ADAMTS -5 is being addressed.....there is scientific evidence out there....you just need to scratch a little under the surface.
This concludes part 1.
Part 2 will further investigate more of the paper and in addition to just more words, we will view a picture that really is worth 1000 words while observing the power and the underlying processes by which iPPS actually conducts it's magic.
The PhD - NO and the DMOAD magic of iPPS... PART 2
In Part 1 we learnt a bit more about the properties of iPPS via a paper submitted as part of a pHD. We read through Study 1 depicting for the first time that it acts as an inhibitor to various biomarkers such as NO ..In part 2 we journey through other studies covered in the PhD paper along with a very clear picture which will give you insight into the workings of the drug that you have invested in.
STUDY 2
Mate, I thought Study 1 was good...The current std of care as we know involves a number of treatments all of which really just results in the temporary reduction of pain and aren't really designed to be on going longer term application. They can result in unwanted side affects and some courses can be addictive. Finally surgery is proposed when it becomes too much in terms of pain and lack of function. "For isolated focal OA cartilage lesions, several surgical treatment options that reduce pain and extend the useful life of the joint, prior to total joint replacement, are available".
The paper refers to Ghosh's work in terms of "PPS was recently shown to promote proliferation and chondrogenesis of human bone marrow-derived mesenchymal precursor cells (MPCs) while suppressing osteogenic expression and bone formation in micromass cultures". The paper went on to assert that follow up studies in this area were lacking, thus Study 2 attempted to "investigate the chondroinductive potential of PPS to completely restore the phenotype of dedifferentiated monolayer articular chondrocyte ".This study again involved dogs, two were chosen .The findings of this study confirms PPS as novel chondro inductive factor with the potential to offer a solution to the major challenges that exist at the front-end of cartilage tissue engineering."
This second study's results effectively confirmed what was originally observed by Collier and Ghosh back in 1989, "These observed positive chondroinductive effects of PPS are in agreement with previous studies ".
Ok before the next quote, let me explain some terminologyedifferentiated is a concept in Biology meaning to undergo a reversal of differentiation, in other words a cell might have had some specialised function it now does not.Monolayer simply means closely packed, dense cells for example. CACs are canine articular chondrocytes, ok this ones needs another level of Mozzifing.... Cananine - dogs Articular Chondrocytes are highly specialised cells which secrete the matrix (scaffolding and network) of cartilage and becomes embedded into it.
*whew* sorry we had to go into that detail as I want you to understand the ramifications of the next quote...we are ready now....
"The study presented in this chapter demonstrated for the first time that the phenotype of dedifferentiated monolayer CACs is completely restored by combining alginate beads with culture in standard medium supplemented with only PPS without the addition of established chondroinductive growth factors."
Paradigmers, they are saying that though sample size was small, they are saying that more research and experimentation needs to be conducted to show this, but this study found that for the first time it was observed that PPS can play a major role in COMPLETELY RESTORING this cartilage matrix.
Now don't get me wrong, I'm not inferring that iPPS will re-grow your entire cartilage form nothing. All I am deducing is that iPPS can help, perhaps not in all circumstances in every patient. BUT I am saying there is some percentage , some chance, that SOME patients MAY get some amazing DMOAD result at least to some extent?Highly speculative remarks and conclusions and you know I'm not a scientist, so please do your own research, all I want to bring to the table is that there is more to discover and I personally I think we really are just getting started here.
We have seen the wonderful results it CAN have on SOME animals and human patients alike, 1000 SAS patients so far with what, about 90% of them showing at least some improvement with a large 50% or so showing 50% reduction of pain and a great 75% or so showing at least 25% reduction in pain. I can't wait till we get more peer reviewed material and more trials to test and focus on the DMOAD properties of iPPS and its potential.Here is another quote from the same study..."...the findings of this study confirmed PPS as a novel suitable alternative chondroinductive factor to known chondrocytic growth factors that may offer a solution to the inherent challenges faced in cartilage tissue regeneration and repair of small OA cartilage lesions."These words mean a lot to us. Even if there is only just a small amount of cartilage tissue regeneration and repair of small oA cartilage lesions, it is transformatory. Leave aside the pain reduction, the safety profile...it is these mirco chain reactions that will disrupt and on what scale.Ok on to another study covered by the some paperSTUDY 4In the next experiment they again took samples from dogs and this time they compared the effect of PPS and a compound known as PSGAG. The evidence and action which we will cover shortly also serves to depict just how vastly different a change to the underlying molecule can have also quoted in the paper: "the study in this chapter demonstrated that while PPS and PSGAG share a similar chemical structure, their effects on chondrogenesis of cBMSCs varies significantly. "PSGAG stands for polysulfated glycosaminoglycan / Now the science is borderline on the fringe for me to understand but from what I gather, there are differences between PSGAG and PPS in that they both do belong to the same family of polysulfated polysaccharides BUT the PSGAGS are primarily derived from " chondroitin sulfate (CS), and the product is made from an extract of bovine lung and trachea modified by sulfate esterification. " (ref 8). "This observation confirms the results of a previous study which demonstrated that PPS promotes proliferation and chondrogenic differentiation of human MPCs s (Ghosh et al., 2010) "Now as I mentioned, the interesting part was that despite these two molecules belonging to the same family, they act in vastly different ways, "PPS synergistically enhanced chondrogenesis and PG deposition whereas PSGAG inhibited chondrogenesis ". Again, read those words carefully...PPS is promotion growth....tis is key, this is what we want, this is the underlying biology and this is what I understand to be INSIDE the black box of what is the workings of our iPPS.for you to drive your car to the supermarket, to the pub...to the shopping centre, it makes very little difference if you know how your car works... , but let me say this, if you want to have an edge and you you are a professional racing car driver, you need to know how the car works, every component what is its capacity, what it can do, how it is held together, what problems can arise, what are the co-dependencies..and the list goes on. In the same way it is for me. I cannot have even a slightly over exposure to an investment to any significant degree if I know this stuff works but I do not know HOW...i want to know the WHY...the workings under the hood....I want to know that this is not just random miracles happening here....yes it is magical, I cannot deny it...but Mozz wants to know what is the trick.behind the magic...when and in how many cases it may not work...and when and what proprtion it prob will work. Yes of course the FDA will go through this is much greater detail than I ever could...but in a way Im front-running them...There is no point in me just passively waiting for them to approve it, some instos come in with their BILLIONS of backing US dollars and buying up every share in existence and then me coming in and buying after they have gone through like some freak category 5 cyclone , TOO LATE! I'm sneaking in paradigmers, under the radar, crawling under the barb'ed wire...shhhh....before the world finds out.This is a party Im preparing for.
PHOTOGRAPHIC PROOF.Sometimes words on a screen gets a bit dry...specialy when it is paragraphs of science....to further illustrate my understanding of some of these experiments at a most fundamental level....lets take a look at some photographs. But I will need to explain what we are looking for:1) Ok so these researchers took 8 samples of a cluster of cells (known as micromass culture) and subjected them to the following over 20 days.2) PSGAG is a similar compound but still obviously different to iPPS with its own molecular composition.3) A negative control is a control group that isn't expected to produce any results, a positive is the onverse, ie it is known to produce results.A) Negative ControlB) Positive ControlC) 1.0 micro grams/mL of PPSD) 3.0 micro grams/mL of PPSE) 5.0 micro grams/mL of PPSF) 1.0 micro grams/mL of PSGAG G) 3.0 micro grams/mL of PSGAG H) 5.0 micro grams/mL of PSGAG They then used a Blue stain that shows up bluer when there is PG Deposition. PG deposition is yet another biomarker. Remember that Paul mentioned there are at least 10 of these kinda markers like ADMTS 5 , MMS 3 and 31. PG stands for proteoglycan. The more of this, the healthy things are, to simplify it, think of it as connective tissues that form bridges (tetrasacaccharide bridges).Right..lets get to the pictures plesase Mr MozzOh one more thing before I show you, remember, the more the blue, the better it is...this is the dye showing up the PG.Ok Par_Peeps...whats the verdict, which ones look the bluest to you?If you said anything other than C D or E, I would order a colour blindness test.if you now scroll up a fraction and cross rerfence what exactly w C D and E were, you will find that all quantities of PPS showed efficacy and yes, the highest dose E happened t be the best result. My fellow shareholders, the underlying science does not lie. This is what it fundamentally looks like under the hood of our amazing PAR VEHICLE. I understand the science is heavy and can be dry but do me a favour, just flick through Reference 1 when you get a chance, no need to even skim through it...just have a glance and almost pick any paragraph at random and you will get a sense of what the science is telling us. CONCLUSIONiPPS we now know is multi actionary.1) It has a postive anabolic effect on articular chondroctyes2) It reduces cartilage destruction via inhibition of the activities of cytokine driven facilitators of Osteo Arthrtis3) It increases the anti-inflammatory cytokines (more on this later in a new series of posts I will be doing)4) It has been recently shown to promote chondrogenic differentiation of human Mpc cells.5) We now have seen vi this pHD study the positive effect of yet another biomarker, the production of Nitros Oxide.6) Again via these studies we have witnessed, "for the first time that PPS is a novel inhibitor of IL-1-induced iNOS, c-Jun, and HIF-1α mRNA upregulation, and iNOS protein-induction and thus may translate to its beneficial effects in treatment OA and prevention of disease progression.". Yes paradigmers, you are reading these quotes, these statements BEFORE MOST of the world. This is not some comment from a celeb. and is merely an opinion. These are statements, quotes from science. These are facts, observations and soon to be FDA/EMA endorsed evidence. (My views). 7) I can only simplify so much, read this quote, yes it gives you an ides of the technicalities but aradigmers, read it anyway, you will get the underlying message:"For successful cartilage tissue regeneration and repair of OA defects by autologous chondrocyte transplantation (ACT), redifferentiation of dedifferentiated articular chondrocytes following in vitro monolayer expansion has long been proposed as the best hope for returning chondrocytes to their native articular cartilage mode of expression prior to implantation. Dedifferentiated monolayer P1 CACs cultured for 18 days by encapsulation in alginate beads under normoxia condition in 20% DMEM supplemented with only PPS demonstrated a full retain to their ‘native’ cartilage phenotype as verified by enhanced synthesis of cartilage-specific gene markers, type II collagen and aggrecan mRNA with complete suppression of type I and X collagen. "In concluding the paper went on to state quite clearly: "...this study verifies that PPS is a novel alternative chondroinductive factor with the potential to offer a solution to the major challenges that exist in cartilage tissue engineering efforts ".Mate...study after study is showing me the science behind what we have. 1) It is occurring at a fundamental level2) Others in the industry have noticed this3) The market in Australia is TOTALLY unaware of this (leave aside the Global market)...they have no time and very little foresight to observe and understand the ramifications of this.4) We are darned early to the party. Do not feel like WISHY WASHY Charlie brown (friend of Snoopy)...."I think I have missed the boat"... "COULD'VE got in at $1.08"....I missed the raise at $1.30....I should've bought more at $2. It was only $2.55 the other day but I didn't have funds ready. Mate...YOU could kick yourself many times over if you have some finds and haven't bought and you look at the share in 2024 and it is $45 ...a share....(my views). Do not feel you have missed the boat now, get SOME exposure (not advice, you must weigh this up for yourself, do not over invest in one investment vehicle, this is in no way advice...)...I don't really care if you just have 300 shares..in my strict view, even 300 shares could actually be worth something half decent in a mere 8 years (yes it has to be a longer time if you have a smaller exposure).I have some people (I want to call them Super PAR holders) lets call them bedrock shareholders, that I'm in touch with that have in excess of 1 millions shares each, I do not joke...you know who you are....these people DO not have to wait for 8 years...a mere 4 years and they will be already fantastically wealthy (if they aren't already). But how about this for an insight...they have even longer term personas than ME. They are calm...they are collected, they care not what the share price does on a day to day basis, yes, they are here for the long term, they are here to stay.
ecently I came across some more research involving our Magic Juice...It's a very involved and in depth report from Japan. Tonight I break this report down somewhat. This paper attracted me because of two reasons:
edifferentiated is a concept in Biology meaning to undergo a reversal of differentiation, in other words a cell might have had some specialised function it now does not.Monolayer simply means closely packed, dense cells for example. CACs are canine articular chondrocytes, ok this ones needs another level of Mozzifing.... Cananine - dogs Articular Chondrocytes are highly specialised cells which secrete the matrix (scaffolding and network) of cartilage and becomes embedded into it.
