Re: The cardiac pre-print now published....in Cell!
in response to
by
posted on
Mar 16, 2021 03:44PM
Tex, I just finished reading the paper. It mentions multiple times that specifically apabetalone reduces cardiac cytokine storms (CS) and completely blocks CS-induced cardiac damage. This is in addition to its COVID anitviral characteristics... 2.6 fold decrease in viral load.
They go further to speculate its usefulness on other inflamation induced conditions like CVD and diabetes...and conclude that apabetalone is the lead candidate for treating COVID-caused heart damage.
Its all right there! Apabetalone is golden!
How can a Big Pharma decision-maker read this paper and not fall out of his chair reaching for the cheque book?
excerpt:
39 We demonstrated that BETi are attractive therapeutic candidates, however the side effect
40 profiles of some BETi may preclude their use in the clinic. Genetic ablation studies have shown
41 that BRD4 plays an integral homeostatic role in cardiomyocytes, suggesting that the loss of BET
42 proteins may have detrimental effects on mitochondrial energy production (Kim et al., 2020;
43 Padmanabhan et al., 2020). Emerging evidence dissecting the roles of BD1 and BD2
44 bromodomains in inflammatory disease models has indicated that BD2-selective inhibition
45 preferentially blocks the induction of gene expression while minimally affecting established
46 transcription programs (Gilan et al., 2020). More recently, BD2-selective drugs such as ABBV47 744 and apabetalone have been developed to overcome these side-effect profiles. Whilst
48 ABBV-744 was not effective in our hCO model (potentially due to its targeting of AR), we
Journal Pre-proof
11
1 demonstrate that BD-2 selective compounds, RXV-2157 and apabetalone demonstrate efficacy.
2 This underscores the need for careful BETi selection, despite broad ability to modulate critical
3 target genes (Figure 6L) and utility for a variety of clinical conditions (Cochran et al., 2019).
4 Importantly, BD2-selective BETi apabetalone reduced CS-induced diastolic dysfunction and
5 downregulated ACE2 and reduced viral infection (Figure 7). Taken together, the efficacy and
6 known safety profile of apabetalone make it a prime candidate to protect against cardiac injury
7 for inflammatory diseases such as COVID-19.