Biotech Values

[iwfal]

niacin -

Are you saying that you do not accept reverse-lipid-transport as a valid MoA and property of HDL's? Or do you have another reason?

Not saying reverse lipid transport doesn't happen. Only that it is one part of a very complex set of interconnected control loops - many of which we only partly understand and some of which might be completely unknown to us at this instant. Then add in the fact that niacin is not a mab - i.e. a very specifically targetted drug - but is more like a shotgun and my conclusion is that it is likely we don't actually know niacin's MOA (if any).

Note that this is hardly unique to niacin/HDL. There has been an on-going significant debate as to whether statins efficacy is really through LDL lowering or not. I think there is reasonable data to suggest that a significant fraction of its efficacy is through something other than LDL - e.g. inflammation effects.

My view in such circumstances is that specific markers indicate what drugs to try, but are not particularly informative about which drugs will actually succeed. The markers get you in the right neighborhood - but do not guarantee you are on the right street.