Hi Koo -
Hopefully someone who is better at speaking with precision can correct this attempt at an answer, but here goes.
No lung issues showed up during BETonMACE because apabetalone doesn't damage the lungs, and no one in BETonMACE had covid, that we know of.
It seems that one of the POTENTIALLY problematic implications/conclusions of this mouse study (not rats as i mistakenly said earlier) is that apabetalone is in a class of drugs that MAY inhibit immune response to covid virus in the lungs. Which is contrary to what we expected.
i woud gather that there probably are no direct adverse impacts to the lungs from apabetalone, or at least none that came up ..during BETonMACE or other trials...
BUT the problem seems to be that the bromodomain apabetalone inhibits has a function in mounting immune response to the covif virus in the lungs.
So, even though dysregulation of BD2 expression can lead to/cobtibute to a whole slew of disease processes, and even though the cooled expression/ inhibition apabetalone provides is USEFUL and helpful in many cases.agains such disease processes..... Even so, based on this single study of 50 rats, it MAY have turned out that the BD2 bromodomain also does have a use, and its inhibition is not useful in the case context of early covid disease/covid pandemic.
Or at least that is the concern.
Some drugs work as therapy for one condition but make patients more susceptible to other problems.
The results of this mouse study seem to suggest that we MAY have encountered that type of situation here, IF this single study of 50 mice is sufficient to reflect the whole of the treatment reality.
A single study may or may not be an accurate or complete reflection of what works and what doesn't. There seems to still be room for further investigation.
As discussed by others above, there may be reasons why the recommendations of this study could be erroneous, and apabetalone may be fine, even as a covid therapy. In fact i suspect it could still prove useful against long covid if given a chance, and useful for ither inducations as well.
The jury is still out as to whether other dosing methods, or other factors or adjustments could still demonstrate BET bromodomain inhibitors as a viable treatment.
BUT ABOUT LUNGS in covid response...my point was just - now that the question of diminished ability to fight covid has been raised, with the evidence of this one mouse study, UNTIL there are further studies that directly address this question, there may be some doctors who would hesitate to recommend that their patients even participate in the trial, given the current prevalence of covid. In fact it could explain trial delay or cancellation. Because once they know there may be this risk, until they have reason to believe otherwise, why would they take the chance?
Even if apabetalone were eventually shown to be a viable treatment for covid, as long as there is limited evidence out there, to have ANY evidence of increased mortality with BET inhibition treatment is very damaging, even if it is not specific to apabetalone per se.
Hope that makes sense
As for the cardiovascular, my comments went ONLY to the question of what would normally be purely life-saving vs. what other risks might need to be considered in light of ongoing pandemic, mutations, variants, etc.
Hopefully they are wirking on further evaluating and addressing this question. But doing so would certainly both explain and justify delays.
