There is zero publicly available data that I know of on how apabetalone affects ACE2 in apabetalone treated patients. All I could find was data in which blood was taken from untreated donors, treated in a test tube or dish with apabetalone, and then assayed for changes in gene expression 24 hours later. This has very limited extrapolation.

1) The apabetalone dose used in that isolated blood study may not be the same as dosing patients.

2) The kinetics of metabolism of Apabetalone when given orally may prevent a blood concentration of apabetalone from ever reaching the dose used in the isolated blood study.

3) A 30% change in ACE2 mRNA in isolated blood study is a pretty modest change in expression. mRNA is translated to protein, and mRNA levels don't always correlate with protein levels. Further, the amount of ACE2 on the cell surface is what is most relevant. Even if they did measure total ACE2 protein, this would not necessarily be cell surface ACE2.

4) An intact whole animal or human has numerous cell types and organs, each of which may be exposed to different amount of apabetalone and may respond differently. One can't generalize expression changes in whole blood to other tissue/cell types.

5) With respect to ACE2 and virus infection, one would want to know what tissue(s) and cell types are relevant for viral infection and replication, and then assess whether apabetalone modulates ACE2 in those relevant tissues. ACE2 changes in a cell that never sees the virus would not be relevant.

"apabetalone has been previously shown to reduce expression of ACE2. However, the only manuscript (after a quick search) that I could find was this one and it was only a modest decrease (30%, -1.3-fold) and it was observed in human whole blood treated ex-vivo for 24 hours. I would feel more confident in this proposed mechanism with some additional confirmatory data showing reduced ACE2 mRNA, total protein and cell surface protein expression in other experiments and model systems."

BDAZ