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Pexidartinib (PLX-3397) -- A new drug for replacing microglia

Jesse2233

Senior Member
Messages
1,942
Location
Southern California
Hey everyone,

I've stumbled across a new drug called Pexidartinib (PLX-3397) that repopulates microglia. It's currently being trialed for cancer and tumors.

I've not seen this drug discussed anywhere in regards to ME/CFS

From a study using adult mice:

Surprisingly, extensive treatment results in elimination of ~99% of all microglia brain-wide, showing that microglia in the adult brain are physiologically dependent upon CSF1R signaling. Mice depleted of microglia show no behavioral or cognitive abnormalities, revealing that microglia are not necessary for these tasks. Finally, we discovered that the microglia-depleted brain completely repopulates with new microglia within one week of inhibitor cessation

So far there have been some liver toxicity side effects in human trials. But if one only needed to take the drug once to restore healthy microglia then it might be worthwhile.

Of course the big caveats are:
  • Microglia may not be central to ME pathology
  • The new microglia may simply get reprimed when they grow back by some other causal factor
  • Wiping out part of the brain's immune system may not be a good idea if there's a virulent chronic pathogen
Nonetheless it looks interesting. I've emailed Jared Younger to get his thoughts
 

Sancar

Sick of being sick ~
Messages
98
Location
So Cal USA
@Jesse2233 ~ Let us know what Jared Younger replies if you would please. Thank you for sharing your insight and findings!!! Very much appreciated!
Perhaps there could be trial with this drug as with others that offer 'conditional relief' and hope.
~~ For many of us a trial would give us both...
 

Jesse2233

Senior Member
Messages
1,942
Location
Southern California
Response from the good doctor after I sent him a link to the mouse study.
I’ll read this one on Wed. Intriguing idea to wipe out the old microglia and allow repopulation with hopefully non-agitated microglia. I’m not familiar with pexidartinib though so will have to see what exactly it does. Thanks –

I'll let you know what he has to say after he reads the study.
 

Little Bluestem

All Good Things Must Come to an End
Messages
4,930
Of course the big caveats are:
  • Microglia may not be central to ME pathology
  • The new microglia may simply get reprimed when they grow back by some other causal factor
  • Wiping out part of the brain's immune system may not be a good idea if there's a virulent chronic pathogen
Even if not central, fixing the microglia might make a person feel a little better, if the other two aren't true.