Indication

Target/marker/pathway

Summary

Licensing status

Publication and contact information

Ophthalmic disease

Age-related macular degeneration (AMD)

ATP-binding cassette
sub-family A member 1
(ABCA1); liver X receptor (LXR); microRNA-33 (miR-33)

In vitro and mouse studies suggest increasing ABCA1 levels or antagonizing miR-33 could help treat AMD. In macrophages from aged mice, increased miR-33 levels caused decreased ABCA1 expression, which led to greater endothelial cell proliferation than that seen in macrophages from younger mice. In macrophages from the aged mice, an LXR antagonist that upregulated ABCA1 expression or an anti-miR-33 oligonucleotide reversed aberrant endothelial cell proliferation, whereas vehicle or a noncoding anti-miRNA had no effect. In a mouse model for wet AMD, the LXR antagonist decreased choroidal neovascularization compared with vehicle. Next steps could include additional animal studies.
AstraZeneca plc and Regulus Therapeutics Inc. have an antisense oligonucleotide targeting miR-33 in preclinical testing for cardiovascular indications.

SciBX 6(15); doi:10.1038/scibx.2013.371
Published online April 18, 2013

Patent and licensing status unavailable

Sene, A. et al. Cell Metab.; published online April 2, 2013;
doi:10.1016/j.cmet.2013.03.009
Contact: Rajendra S. Apte, Washington University in St. Louis School of Medicine, St. Louis, Mo.
e-mail:

apte@vision.wustl.edu