PAR and the BML findings

uite simply, Bone Marrow Lesions are a build up of fluid within the bone marrow.

Tonight we cover more on what exactly is this BML is, what the ramifications are but even more importantly, how YOU as an owner of this magnificent company is actually doing something about it and why I think the future is bright because of it....

A Two part'er tonight, too much material to even contemplate just one post...in truth, to cover this properly it would involves pages and pages...but lets tackle it at a higher level. A higher level doesn't just mean superficial. You are passing another Mozz Post...this means I will endeavour to cover the theory...cover the science...but also link it to what YOU own....


_{LINFOX has some 5000 trucks in the total fleet. Yes indeed, Lindsay started with just ONE truck. One day I will get to some such number in Major Mozz posts!}

(Remember the French MD and PhD I met at Oarsi? The one that exclaimed that I do this for a Hobieeee? He also stated that it all starts with one patient when I showed him Adherent's MRI's)



DEFINITION

Bone Marrow Edema is simply an increase in interstitial fluid within the bone marrow itself. Typically its characterised by pain and often it occurs without an obvious cause.¹

Is a particular word in that fluid sentence above ringing any bells for you guys?



_{Are these ringing for you guys? Where have we heard interstitial before?}


Yes the word interstitial we have seen and heard in the condition known as interstitial cystitis (IC). How is this relevant to us? Pentosan in the pill format has been used to address this condition for decades. We are repurposing this same molecule in a Sub Q format. The word interstitial pertains to areas around the cells or walls eg the bladder wall in the case of IC. The fluid itself may not be bad, think of it as a pool of fluid surrounding cells. Its this fluid that helps to bring oxygen and nutrients to the cells and helps to remove the wastes.

Its when, like a lot of the things with the body, the equilibrium is disturbed, the balance is knocked off and you get too much fluid build up, that's when problems start to occur..

The science here is still being discovered but it is thought that BMLs are associated with pain due to the increased pressure of this fluid within the bone. Aggravation of neurovascular bundles is the technical term here.







EXAMPLES

Ok so we get a sense of what these BMLs are, but what do they look like, a picture is worth a thousand words?



The arrows point to the cloudiness in the MRI...we don't want the clouds...less clouds, more clarity...Yes I can go for a lovely walk with a good friend in a nearby park...but its so much more enjoyable when the sun does shine (and there is no pain in our knees!!)


Mozz mate, I enjoy the theory, really I do, BUT when oh when would we get some real life case studies involving our own iPPS?

So glad you asked:



A, b ,c before iPPS, d, e and f is after, remember, less cloudiness! ³

The above was taken from a 70 year old woman who went through the course - percentage reductions due to the magic of iPPS?

Guesses? Anyone?


It must be time for a Mozz Quiz^®



QUESTION: WHAT PERCENTAGE REDUCTION DID THE 70 YEAR PATIENT OBTAIN IN TERMS OF HER BMLs AS A DIRECT CONSEQUENCE OF iPPS TREATMENT?




A) A solid 10% decrease?





B) 12% ?




C) Can't be more than 17% right?




Read this for the answer:

The MRI findings performed using a 3-Tesla proton density fat saturated SPACE acquisition with TR 1200 ms TE 28 ms demonstrated that a course of intramuscular PPS produced complete resolution of the BML at the medial femoral condyle and medial tibial plateau.




Yeah, it's D) 100% complete resolution !!!?!!



PAR holders, I again ask you...what do we own?

My own view...ignore the Share price disconnect, it means very little. Of course its not just the science that we need right...we need the commercial side to come to play as well...In my own personal opinion, this will happen one day.



HOW COULD IT BE WORKING?


We know iPPS addresses inflammation. But as focused investors this answer is still quite a black box. When I buy a new car (something I haven't done for 12 years now...yeah I'm waiting for you know what) - I want to know more about my new car. I'm not the kind of person that will just take possession and be oblivious to 60% of it's functions. Nah I would go all out and read the manual and know every aspect of my new car...when I buy a new car I don't just hold it for one year....It's quite the same for my stock of PAR. I want to know all about it...


So lets talk some more about the Bone Marrow and it's interaction...for that, we must know a little about the lymphatic system:




_{Example of a lymph node.}


The lymphatic system is responsible for a lot of the body's immunity, it's ability to fight a lot of the outside germs that enter in. In fact there are four main functions of the lymphatic system.⁴


Protecting your body from illness-causing invaders


Maintaining body fluid levels


Absorbing digestive tract fats



Removing cellular waste




The bone marrow is one of the repositories for the lymphocytes, the cells that make up the lymphatic system. These need to be regulated and here is where iPPS enters the stage...





PPS treatment in RA and OA patients may prove beneficial as well as for diseases with strong lymphocyte inflammation like lymphocytic colitis.





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PPS was shown to exert effect on growth factor signalling, lymphocyte activation and pathogen response, all which likely contribute to the amelioration of CHIKV-induced arthritic disease.






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The above two quotes actually came from our own pre clinical study in CHIK-V.¹²




Typical red marrow bone topology looks something like this.⁵ :





But what can accelerate the conversion of the lovely young red marrow to yellow?


Smoking


Anemia (lack of red blood cells)


Obesity




But don't forget, its not just traumatic causation of a instigation and/or progression of BML, think also of infectious, neoplastic and of course inflammatory causes.⁶

One of the most prevalent ways BMLs can progress is through the inflammatory pathways. We know how iPPS works here, the arresting and down regulation of the 'Grand Daddy' of the inflammatory cytokine pathways, NFkB.


Lets have a look at where NF-kB fits in the inflammatory flow:





Mate, now that's what I would call central.

New guys to us? iPPS, our drug, has shown to downregulate and address this (What I like to call) 'Grand-daddy' of the inflammation triggers.
Remember, important note, we do not want to irradiate such Grandaddies...we need some, its part of the natural immunology of the human body. We want to ensure its not runaway...this is key in my view.






That concludes Part 1. It's in Part 2 we take it up a notch....we will discuss BML's as markers, we will see their potential and we will take the theory and explode it into a practical illustration, yes, we will see how our very own molecule performs here for a sneak peak through the window into possibly our bright future.