Expanding Horizons - The AI response

'm slowly starting to to post more over at Reddit. It's a vast world out there.

Yes of course HC is my home and I will always post new stuff here first. At the end of the day I want more eyes on us and I want longer termers on our books. I want a stable Share Register for ol' PAR. It helps me, it helps you (unless you are a day trader and you dont care so much, in that case why are you even on HC reading all these more in depth posts about science, stats and everything else?).

But tonight I want to post a little on something even I was nicely reminded of.
Let's explore.



THE SLOWLY, SLOWLY APPROACH

Over at Reddit there are a lot that have never heard of Pentosan and you get a stack of questions, That's why I have to take a very slowly, slowly approach. I have only a little bandwidth to spend too much time over there entertaining all sorts of questions. So the easy way is to start small, that means getting a sub thread that only has a comparatively lower number of subscribers. Eventually, when I go full time on this... ...well I can hit those bigger boards hard! (Wait till they see their first Mozz Quiz ® over there heh heh)

As an example, we have around 600 people that traverse through our PAR threads. The OA group over there has some 9000, the Biotech and Pharma Stock group has some 17,000 members and the Back Pain Reddit group has 58,000 !



THE QUESTION

So the other day, out of the blue, a Reddit user posts the following comment in response to an MRI image I showed them:


Yes there are some indications that osteochondral issues can be addressed by our Pentosan (Think of osteochondral lesions as insults typically as a result of injury, typically a tear and/or fracture of cartilage and perhaps the underlying bone. But I focused more on that last few words above, can cartilage be repaired by Pentosan?

*Mozz Rubs his hands together* ...this is one statement I have to address....but I thought for a sec, I know there is a plethora amount of info I've come across the years supporting this but why not run this by a process that I've been experimenting more and more with just recently.

ENTER AI

I'm very comfortable with how much research there is on Pentosan and how it can repair cartilage. You have to be a little mindful of the AI generators, they are really excellent in summarising and laying out logically an intro, body and conclusion. They are brilliant at summarising stuff. But you gotta watch the content a bit, specially using the freebie versions.

There is definitely some good logic there and I have used it to plough thru some stats and it's worked really well. This tech is only going to get so much better over the months and years to come. I'm also starting to see better thought responses, there is good evidence of them actually formulating great logical, probability based conclusions, rather than just brute force quick computational prowess.

So I wanted to put AI to the test to see what it can gather on cartilage regrowth but specifically linking that with Pentosan. So I feed this into Google's AI known as Gemini...

I got this answer (I'll put AI's answers in lavender so it's easier to distinguish my notes from it).

Pentosan Polysulfate Sodium (PPS) is a medication that has shown promise in the context of cartilage health and osteoarthritis, but it's important to understand its precise role.

While PPS is not definitively proven to "grow" new, healthy cartilage in the same way that a young, healthy joint would produce it, research suggests it has several properties that can improve cartilage health and potentially contribute to repair mechanisms:

Chondroprotective effects: PPS is considered "chondroprotective," meaning it helps protect existing cartilage from further degradation. It does this by:

• Inhibiting destructive enzymes: It can reduce the activity of enzymes (like MMPs and ADAMTS) that break down cartilage components (e.g., aggrecan, collagen).
• Stimulating cartilage matrix synthesis: It can encourage chondrocytes (cartilage cells) to produce more proteoglycans and other components of the cartilage matrix.
• Maintaining proteoglycan content: It helps preserve the vital proteoglycan content within the articular cartilage, which is crucial for its shock-absorbing properties.
• Anti-inflammatory properties: PPS has significant anti-inflammatory effects, which are critical in osteoarthritis as inflammation contributes to cartilage damage.
• Improved joint environment: It can improve the quality of synovial fluid (the joint's natural lubricant) and enhance blood flow to the subchondral bone (the bone beneath the cartilage), which is important for cartilage nutrition.
• Potential for stimulating repair: Some studies suggest that PPS can promote the proliferation and differentiation of mesenchymal stem cells towards a chondrogenic (cartilage-forming) phenotype. This indicates a potential for stimulating repair processes, though more research is needed to fully understand the extent of new cartilage formation in humans.

In summary:

PPS is widely researched as a disease-modifying osteoarthritis drug (DMOAD). This means it aims to slow or reverse the disease process, rather than just masking symptoms. While it may not regrow large amounts of lost cartilage, it appears to be beneficial in:

Reducing cartilage damage.Improving the health of existing cartilage.Potentially stimulating some level of repair or maintenance.Reducing pain and improving joint function in osteoarthritis.

The evidence for its effects on cartilage improvement is growing, with promising results from both animal models and human clinical trials, particularly in conditions like knee osteoarthritis with bone marrow lesions.

If you are considering PPS for a medical condition, it's essential to consult with a healthcare professional to discuss its suitability and potential benefits for your specific situation.

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Lovely. so I was fairly happy with the response above and it gathering info to hint that there are restorative properties at play and that the evidence is "building". I was also impressed that it seemed to be giving me it's conclusions rather than just merely parroting back what it could muster and presenting it well. I don't care as much for it's concise presentation, I wanted it's opinion based on the vast libraries of information at it's cyber fingertips.

But I wasn't fully satisfied as there was no real in depth and specific mentioning of anything definitive and more substantive specific to DM connotations that you and I know so well. So I thought....


LET'S GO DEEPER

I then thought I would guide it towards PAR's 008 Phase 2B research and results. I know that was well controlled, yes, small numbers, but achieving statistical significance is a great start in a well controlled, multi site, double blinded study. So I even fed it a link so it wouldn't have to work extra hard in searching for it.

So I wrote this into it's little input box:






.

Mozz Note: Here is the link in case any of you new guys haven't come across it (simply left click on the below hyperlink):

https://app.sharelinktechnologies.com/announcement/asx/058732021c8928f27d89da8502ca692a


Possibly one of the most stunning announcements ever from PAR to date, this was the article I pasted into the AI input box.



Anyway, back to the AI story...so what did ol' Gemini the AI wizard come back with? How many pages of response did I get back?






None.


A DEAD END!




I got this mind cancelling response:


I am unable to access the content of the provided link directly to evaluate if it changes the previous answer, as the link points to a PDF file that I cannot process in its current format. Therefore, I cannot incorporate the information from that source into my previous explanation about Pentosan Polysulfate Sodium (PPS) and cartilage growth.



Dam*...

So much for that. Looks like I will have to wait for another year or two to let the tech improve???


....but does Mozz pack his research bags and give up?


No way...so I spoon feed the AI baby with the big brain:




I copy the ENTIRE PAR 008 ASX announcement and paste it all into the AI Box hahahah


Now this is what I get...mate, just take a read of this: (and BTW, those bold highlights and italics are it's highlights, not mine!)



Yes, the evidence provided significantly strengthens and adds crucial details to the previous answer regarding Pentosan Polysulfate Sodium (PPS) and its effect on cartilage.

The ASX release from October 18, 2023, concerning Paradigm Biopharmaceuticals' PARA_OA_008 phase 2 clinical trial, provides direct quantitative evidence that injectable Pentosan Polysulfate Sodium (iPPS) can increase cartilage thickness and volume in individuals with knee osteoarthritis.

Here's how this evidence changes and expands upon the previous answer:

Key Updates from the Provided Evidence

Direct Cartilage Growth/Increase: While my previous answer stated PPS is "not definitively proven to 'grow' new, healthy cartilage," this release
presents strong evidence of an increase in cartilage thickness and volume.

• Participants receiving the optimal iPPS dose saw an average increase of 60 µm (0.06 mm) in cartilage thickness in the central medial femur at 6 months, compared to a loss of 20 µm (-0.02 mm) in the placebo group.
• Overall cartilage thickness across all knee compartments increased by 0.17mm in the iPPS group compared to a 0.09mm decrease in the placebo.
• Overall cartilage volume increased by 1.9% in the iPPS group, while the placebo group experienced a 1.58% decrease.
• The document explicitly states, "The above results support that iPPS both treats the symptoms of OA and preserves and/or regenerates joint tissues." It further adds, "This data again demonstrates iPPS is reversing the breakdown of cartilage at 6 months."
• Disease Modification Confirmation: The trial results strongly support iPPS as a disease-modifying osteoarthritis drug (DMOAD). It not only addresses symptoms but also demonstrates structural improvements to the joint.
• This is highlighted by the reduction in bone marrow lesions (BMLs) by 17% in the iPPS group (compared to a 2% increase in placebo) and a decrease in synovitis (joint inflammation) by 1% (compared to a 4% increase in placebo). These are crucial indicators of underlying disease progression.
• Quantitative MRI Data: The use of quantitative MRI analysis provides objective, numerical measurements of these changes, which is a more robust form of evidence compared to qualitative or semi-quantitative assessments.
• Durable Effects: The study shows durable pain and function improvements over placebo out to Day 365, indicating a long-lasting effect from a relatively short 6-week treatment course.
• "World First" Claim: The release claims this Phase 2 randomized controlled trial appears to be a "world first showing... Increased cartilage thickness and increased cartilage volume at Day 168, while placebo showed a reduction in both cartilage thickness and volume."

Updated Conclusion

Based on this new evidence, the previous answer can be significantly updated to reflect that Pentosan Polysulfate Sodium (PPS) has demonstrated the ability to increase cartilage thickness and volume, reverse the breakdown of cartilage, and reduce other structural markers of osteoarthritis progression, such as bone marrow lesions and synovitis, in individuals with knee osteoarthritis. This positions PPS as a strong candidate for a disease-modifying therapy, going beyond just symptomatic relief.

This is a very exciting development in the field of osteoarthritis treatment, suggesting a potential for true structural improvement and not just protective or anti-inflammatory effects.

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Mate it is telling ME that this is a "VERY EXCITING NEW DEVELOPMENT in the field of OA treatment".




As a response to it, I should've typed in something like "Thanks AI Gemini Buddy-Pal-Chum, I know this, oh how I know this".



CONCLUDING...


The world of AI is changing the landscape at quite a clip. We are still in the early days of this technology but it is very helpful and is already saving us heaps of time. One quick example. Man from the West and I, about a year and a half ago, spent quite a bit of effort to compute out what a reasonable n would be after the 008 result. I had to traverse through a number of websites back then to get stats formulas I could use to manually calculate it. We had all the inputs A, B, C, D (for example) to spit out x.

Nowadays, all that is simply achieved in 2 seconds via these AI generators. You just feed it stuff like the power, the drug effect size, the Alpha and it will tell you what min. n you need to have, or the prob of success if you know the n etc. At the end of the day, we can extrapolate a lot and we can get better at predicting the ultimate risk.

But finally, we successfully get through our P3 and it's going to make the PAR company a very, very different beast indeed.










Not advice






REFERENCE

1) https://www.cedars-sinai.org/health-library/diseases-and-conditions/o/osteochondral-lesionsosteochondritis-dessicans.html2) https://app.sharelinktechnologies.com/announcement/asx/058732021c8928f27d89da8502ca692a