Abstract - first example of a "curative" effect?
posted on
Oct 10, 2018 05:28PM
The abstract at the end of the link below is a little interesting. While many papers have described how BET inhibitors mitigate the effects of inflammation on a wide range of age related diseases, this is the first time I have come across an example where they concluded that treatment with a BET inhibitor was "curative?" for a disease. Here is the salient part of the abstract:
Treatment of SSc PDFs with a HAT inhibitor (HATi) was sufficient to deactivate TGFB2 enhancer activity, but full epigenetic activation of the enhancer rebounded after drug removal (my comment: HAT inhibitors worked, but when the effect was lost upon drug removal). We posited that this epigenetic memory—analogous to regulation of inflammatory enhancers—might be initiated by inflammatory effectors (e.g. NF-kB) and enforced by BRD4 recruitment. In support of this hypothesis, we found high NF-kB and BRD4 occupancy at the TGFβ2 enhancer in SSc PDFs. Treatment with the NF-kB or BRD4 inhibitor normalized TGFβ2 expression and the FSR, which was now refractory to drug removal (my comment: refractory to drug removal is the keyword - I take that to be the same as curative).
While Don said at the AGM that the effect of RVX208 was gone when you stopped taking the drug, I take the liberty of suggesting that this may not necessarily be so. Time will tell.
https://acr.confex.com/acr/2018/meetingapp.cgi/Paper/73874
(I wish they would tell which inhibitor they used, but I suspect it was JQ1.)
I have been (and I still am) very busy since November last year, thus not much in the way of posting from me :(
Best regards,
BKC