Letters Section Editor: Stephen J. Lurie,
MD, PhD, Senior Editor.
In Reply: We agree with Dr Kim and colleagues
that it is unlikely that HDL particle size represents the protective mechanism
underlying the observed effects of ETC-216. Kim et al also point out the absence
of a well-defined mechanistic explanation for the observed benefits of ApoA-1
Milano in carriers or following therapeutic administration. Now that we have
preliminary evidence of a rapid regression of atherosclerosis in human subjects,
we hope that our study will encourage further exploration of the molecular
and cellular mechanisms of action of ApoA-1 Milano. Such efforts could provide
important insights into the process of reverse cholesterol transport and lead
to development of other approaches to achieve regression of coronary disease.
Currently, the same team that developed ETC-216 is beginning human studies
of a small molecule that appears to provide similar benefits and would be
much easier to manufacture than a recombinant protein such as ApoA-1 Milano.
If this peptide mimetic produces similar results to ETC-216 in human studies,
it would establish the principle that the full ApoA-1 protein is not required
to activate the reverse cholesterol transport system.
Nissen SE. ApoA-1 Milano and Regression of Atherosclerosis—Reply. JAMA. 2004;291(11):1319-1320. doi:10.1001/jama.291.11.1320-a