Targeting Activin-Like Kinase-1 (ALK-1) for Treatment of Homozygous Familial Hypercholesterolemia

Atherosclerosis is initiated by sub-endothelial accumulation of LDL.
Endothelial cells can take up LDL independent of the LDL Receptor (LDLR).
A GW siRNA library screen identified ALK-1 as a mediator of LDLR-independent LDL uptake.
Loss of ALK-1 leads to reduced endothelial LDL uptake in vivo.
ALK-1 antibodies or decoy proteins are under evaluation as potential therapeutics for atherosclerosis.
A provisional patent application has been filed.
Publication: Nat. Commun. 7: 13516 (2016). http://www.nature.com/articles/ncom ms13516