Designed Ankyrin Repeat Proteins: A Look at their Evolving Use in Medicine with a Focus on the Treatment of Chorioretinal Vascular Disorders

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:

• Mayo Clinic Department of Ophthalmology, 4500 San Pablo Rd., Jacksonville, FL,United States

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.

Cite this article as:

Smithwick Elizabeth and Stewart W. Michael *, Designed Ankyrin Repeat Proteins: A Look at their Evolving Use in Medicine with a Focus on the Treatment of Chorioretinal Vascular Disorders, Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry 2017; 16 (1) . https://dx.doi.org/10.2174/1871523016666170502115816

DOI https://dx.doi.org/10.2174/1871523016666170502115816	Print ISSN 1871-5230
Publisher Name Bentham Science Publisher	Online ISSN 1875-614X