Ann: First Patient Dosed in MND Phase 1/2 Trial, page-172

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Jockthegreat

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01/07/23

10:25

Post #: 68566117
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Originally posted by Densy: ↑

I'm pretty sure I've posted this before, but here's a reminder of why MPL vs MND looks so promising:

https://www.nature.com/articles/s41598-021-97405-1

For those who want to skip to the punchline...

In plain English, at doses greater than 0.4 micromoles, rapamycin seems to be working to down-regulate the mTOR C1 pathway and induce autophagy in motor neurones, clearing out the build-up of misformed proteins that are a hallmark of MND and 'rescuing' these cells.
But wait!
Once the dose of rapamycin exceeds 1 micromole, it becomes toxic. Toxicity also seems to increase over time, even at lower doses. So, while higher doses and extended treatment times may be better for inducing autophagy (which is what we're chasing) you also poison the patient. This is known as dose limiting toxicity.

This is why MPL look so promising!

As an mTOR inhibitor, preclinical research shows that MPL induces autophagy and clears misfolded proteins in a similar fashion to rapamycin but without with same dose-limiting toxicity. MPL is known to be a pretty benign drug.

As those who've seen the MND webinar will appreciate, a great deal of research and preparation has informed the trial and there are very good reasons to expect big things.

Now add in the apparent ability to more than double life expectancy in canine lymphoma (and how this is likely to translate to human cancer).

Plus the antiviral applications.

Of course I'd love it if PharmAust had an entire drug development department with hundreds of staff that could make it all happen at once - but we don't.

Which means everything takes longer, but it is most definitely happening people.

Cheers

Densy

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An interesting post to revisit while we await the outcome on Tuesday...

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Ann: First Patient Dosed in MND Phase 1/2 Trial, page-172

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