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29.5¢ paradigm biopharmaceuticals limited..

Thanks for that. It seems there is an accumulating weight of...

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RTheo

397 Posts.

79

25/03/24

10:37

Post #: 73039570
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Originally posted by Mozzarc: ↑

Rtheo, another example for you (AND THE FDA!!)...the 2mg/kg again seems to be the sweet spot, here is a presentation at the 35th MPS family symposium where DR Simonaro produced this slide of their results:

The 2mg was the best dose in terms of GAG accumulations (you want to see little to none of the blobby white turgid cells like in the top right MPS pic below):

The black arrow shows the near normal conditions iPPS brings back the tissues and cells at the 2mg dosing...whereas the 4mg/kg isn't too bad but not as good (You can see in bottom right part of the 4mg/kg that there are still a number of turgid (Swollen white) cells where GAG accumulations is still taking place).

The above can be viewed more clearly in the video (and Dr L. Simonaro explains it too) at about the 9m mark.

At the 9:10 mark or so she presents it as a bar chart:

Its virtually an inverted Bell Curve depicting the 2mg dose at the peak and the 4 and 1 dosings a bit lower on the 'efficacy curve'.

Here is the ref:

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Thanks for that. It seems there is an accumulating weight of evidence that something around 2mg/kg is indeed optimal but we don't understand much about the underlying mechanisms that limit efficacy at higher or lower doses. I imagine those mechanisms are complex.

PAR Price at posting: 36.5¢ Sentiment: Hold Disclosure: Held
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