APLN17 analog identified for abdominal aortic aneurysm

INDICATION: Aneurysm

An analog of APLN17 could help treat abdominal aortic aneurysm (AAA). Levels of APLN, which is processed into APLN17 and other APLN peptides, were higher in diseased aorta from AAA patients. Testing 35 analogs of native APLN peptides yielded an APLN17 analog that bound its receptor, APLNR, and activated forms of the G proteins GNAI1 and GNAI2 with about five- to 16-fold lower affinity than the native peptide (EC₅₀ values of 8.81 and 3.63 nM for the analog vs. 0.54 and 0.69 nM for native APLN17) but with a longer half-life (plasma levels of ~1,050 nM at five minutes post-administration vs. 0.2 nM for the native peptide). In a mouse model of the disease, the analog decreased mortality, aortic lumen dilation -- a marker of disease -- and cell death in the aortic wall and preserved aortic compliance, which is associated with lower risk of AAA rupture...