Target Occupancy Study (TOS), page-17

Hi II,

Firstly thanks so much for posting the TOS info.


I have screen shot the publication you posted for ease, a lot to scroll through.




There was dramatic uptake of Xanamem in all regions of the brain (except the cerebellar cortex with lower uptake as you highlighted in your post) Uptake was dose dependent, figures within the study above.

That is an interesting question why uptake would be lower in the cerebellar cortex & across all patients obviously so is this structural, dependent on the levels of receptor binding sites in different parts of the brain (ie lower in cerebral cortex therefore less uptake)?

This is an interesting article which I think may help to answer that question:

https://www.researchgate.net/publication/49670823_11b-Hydroxysteroid_dehydrogenases_and_the_brain_From_zero_to_hero_a_decade_of_progress

This could be a question for Dr Gourlay whether that was an expected result for uptake in the cerebellar cortex based on brain physiology as it appears that levels of receptor sites are variable across brain structures in the above article.

Looking forward to PartA readout of XanaMia, which will be used in correlation with TOS data for optimal dose. That’s what interests me the most. Happy with the outcome of this study.

I can’t see where the authors were questioning the validity of the Merck tracer in your link II?

AFAIK this was an Investigator Initiated study first in human for the tracer that used Xanamem in the study, so 2 focuses of the study. I guess it came down to trialling this tracer & what was available at the time.

GLTAH