Title:Designed Ankyrin Repeat Proteins: A Look at their Evolving Use in Medicine with a Focus on the Treatment of Chorioretinal Vascular Disorders
VOLUME: 16 ISSUE: 1
Author(s):Elizabeth Smithwick and Michael W. Stewart*
Affiliation:Duke University, Durham, NC, Mayo Clinic Department of Ophthalmology, 4500 San Pablo Rd., Jacksonville, FL
Keywords:Abicipar pegol, antibody alternative scaffold, anti-VEGF therapy, chorioretinal vascular diseases,
designed ankyrin repeat proteins (DARPins), extended dosing period.
Abstract:Background: Antibodies constitute an important drug development platform for
drugs to treat several ophthalmic, oncologic, and immunologic conditions, but due to limitations
inherent in antibody production and structure, a wide range of other protein binding
scaffolds are being investigated. Designed ankyrin repeat proteins (DARPins) are simple to
produce and offer a range of advantages over antibodies because of their stability, high
binding affinity, and rigid structure.
Objective: DARPins are being developed for a wide variety of medical applications, and the
most studied molecule, abicipar pegol, is used to treat chorioretinal vascular diseases. This
mini-review will discuss the current state of DARPin technology and will summarize drug
development with a focus on abicipar.
Methods: PubMed searches with keywords “DARPin” and “designed ankyrin repeat proteins”
were performed and the reference lists of identified articles were examined for additional
research material. Studies using DARPin molecules were identified at Clinicaltrials.
gov. Non-peer reviewed data were found through Google searches of pertinent websites.
Results: Abicipar prevents angiogenesis by binding all isoforms of vascular endothelial
growth factor (VEGF)-A with single-digit picomolar affinity. Abicipar has a long intraocular
half-life in rabbits and has produced promising results in pre-clinical studies. Pivotal
phase III registration trials for the treatment of neovascular age-related macular degeneration
are ongoing and a phase II/III trial for the treatment of diabetic macular edema has been
announced.
Conclusion: Abicipar pegol has the potential to effectively treat chorioretinal vascular conditions
with an extended duration of action beyond those of currently used anti-VEGF
drugs.
