ur articular cartilage undergoes many biomechanical forces over time. Tonight, we journey through one of the major molecules that assists us in providing the load bearing properties in our joints and surrounding tissues.
But as I said in last week's post, you are passing another Mozz Post. This means we won't just cover the science ...we cover it's material application to what you and I own.
Please now enjoy.
THE MOLECULE
Aggrecan is known as a proteoglycan. This is starting to remind me of the old days when I had not one but three screens....one to look up a definition, the second to look up words within that definition sentence and a third to actually write about the explanation of what I was seeing on screens 1 and 2.
It's like the movie Inception, dream within a dream, except its screen within a screen!
Mate, please give me staff. One day I will set up an office to do just this and I can churn these Mozz reports out bi-weekly! *blah*.
The word proteoglycan comprises of two parts, Protein and Glycan. Glycan simply is a sugar or group of sugars. Think of a proteoglycan as a structure comprising of a few molecules that serve some really cool, some really important functions...examples?
Provides hydration
Provides swelling pressure tot eh tissues enabling them to withstand compressional forces
Assists in cellular processes such as adhesion, proliferation, migration and a number of others
What does this molecule look like?
Yes the above is a mock up to show it simplistically. Below is an actual picture but to make more sense of it they add a dye/stain to it so we mere mortals have some hope of identifying what's what.
The white arrow depicts one of these Sugar chains... Yes its no coincidence that our wonder miracle drug is predominately a natural sugar, pentose. (Yeah that 200 nm there, that is one 200 millionth of a metre!)
Proteoglycans themselves are anchored to the surface of cells or traverse the cell membrane and here is where they get involved in signalling. We know Pentosan also plays a vital role in signalling. Much more to be studied and researcher here though. Signalling is not a single Mozz post, it would be a series. PGs are quite prolific in regions such as the joints, cartilage and the cornea within the eye. They also play vital roles in wound healing and again, we know pentosan plays a large role in the assistance of wound healing.
LOVELY BUT RELEVANCE PLEASE?
Mozz I do so love the science, the stories...but what if anything does it have to do with me and my share holding? Can't we make this a tad bit relevant to what we have and what we one day will distribute?
What I'm asking is, is there any empirical evidence on what iPPS can do for Aggrecan?
In a word....ummm...
YES
Do me a favour - Take a look at this chart:
Mock = Control RRV = Ross River Fever
The researchers put it this way3:
"Pentosan polysulfate treatment counteracts the dysregulation of the cartilage matrix components caused by RRV infection. PPS treatment significantly reduced the early expression of aggrecan and collagen II and the expression of ADAMTS-5 and TIMP-3 at peak disease".
That's from our Chik_V studies...For those that are very new to us, PAR have investigated models of Chikungunya and Ross River fever which are known as alpha viruses, basically producing arthritis as a result of these mosquito borne diseases. The evidence to date has been great but PAR now are focused on the dual programs of MPS and OA.
Great Mozz....love the scientific evidence...and understand this is from an indication that's important but not large scale and this observation was some time ago...can we have something a tad more recent and a bit ore closer to a bigger indication....I dunno...how about OA!!!!
Well what about our 008 program...
Mate...what is this data saying?
THE BIOMARKER
The KOL's have singled out 4 of the very best biomarkers...these have real and worthwhile repercussions for all of us shareholders. They are single handily showing us that iPPS works on them, they are reduced and can potentially act as a surrogate. I can't express to you how important this is for our programs going forward. This science is screaming at us. Don't forget, ARGS has been suggested as a potential OA biomarker by a number of different researchers in the past, here is an example of some quotes:
"The presence of increased levels of aggrecan fragments in synovial fluid has been used as a marker of ongoing cartilage destruction in osteoarthritis". 4
and this:
"There is strong support for using biomarkers for understanding OA, reflecting degradation and formation of the joint tissues, focused on type II collagen and aggrecan". 5
This one from a paper for the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis convened to discuss the value of biochemical markers of matrix metabolism in drug development in osteoarthritis. Good to have the Europeans equally aware of what biomarkers are relevant and offer a potential look through into the progression of OA:
"Many currently investigated biomarkers are associated with collagen metabolism in cartilage or bone, or aggrecan metabolism in cartilage". 6
Finally the relevance of biomarkers, particularly as a surrogate should not be lost on you, the longer term holder. OA we know is a disease that progresses very slowly over years if not decades....but we have a drug here that can potentially address this. Not only that, there are real merits of getting onto this drug EARLY...when micro fractures in the cartilage are present. How can we ever detect these other than conducting a MRI? Potentially through the bio markers.
I'm not just talking prophylactic, I'm talking about the chance of an Accelerated on the horizon. Yes we have some milestones to still tick off....but no one, and I mean no one is going to know exactly when this babe gets filed until we get that out of the blue trading halt...watch this space. (Accelerated filing not guaranteed, my opinion expressed).
Again, a word of caution, we do need to see these results replicated in a larger set of patients...we do need follow up studies, this isn't necessarily an over night proposition...but if you can....if you will...hold on....just like those crazy hardened barnacles of anchor man's steel propellers that he tells me about....that can only be burnt off with a good dose of HCL (Hydrochloric acid for you landlubbers) or some sorta super scrapper....I believe we have something here worth holding on to!
Blistering barnacles, these blighters hold on! I want to be like them...$1.02 a share? It's *so* BUYING time...I have a good feeling on what's coming (Spec comments, do not rely on one [insane] poster, not advice to buy/sell).
A mere 100%...300% won't cut it for me. Maybe I'm a bit alone with these thoughts, but I have a feeing this will change over time as the weaker holders get flushed out. Don't let these insto smarty pants rob you retail holders! (My views)
...and despite the n being very low on our viewing of ARGS...what was the final p value here...check out the red circle below?
Magnificent!
The thing with ARGS is that it is coupled to cartilage degradation...it's like a horse and cart...
...the horse is ARGS in this case but the cart of cartilage follows in tandem:
ARGS is just one of the magnificent 4 biochemical markers that have been identified and commended as a focus area, couple this now with structural observations such as the BML regression data and that bio book that PAR will ultimately submit to the agencies will be quite a darned read. None of us know how and when this will play out but I think there is one thing we all can't deny...week by week we are getting closer to our real shot at goal.
Kick this one through and it could just be a world beater on a scale we really just can't properly imagine...
ur articular cartilage undergoes many biomechanical forces over time. Tonight, we journey through one of the major molecules that assists us in providing the load bearing properties in our joints and surrounding tissues.
Provides hydration
Provides swelling pressure tot eh tissues enabling them to withstand compressional forces
Assists in cellular processes such as adhesion, proliferation, migration and a number of others
(20min delay)