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Eur J Pharm Biopharm. 2015 Sep;95(Pt B):158-72. doi: 10.1016/j.ejpb.2015.02.020. Epub 2015 Feb 26.

Antibody therapies and their challenges in the treatment of age-related macular degeneration.

Author information

1
Department of Ophthalmology, University Hospital Regensburg, Regensburg, Germany.
2
Department of Ophthalmology, University Hospital Regensburg, Regensburg, Germany. Electronic address: diana.pauly@klinik.uni-regensburg.de.

Abstract

Age-related macular degeneration (AMD) is the leading cause of vision loss in the western world. This multifactorial disease results from the combined contributions of age, environment and genetic predisposition. Antibody-based treatment of late-stage neovascular AMD with inhibitors of vascular endothelial growth factor has had great success, which is now the goal for currently untreatable AMD manifestations. The existence of an immune-privileged environment in the eye supports the feasibility of localized antibody therapy. Many different antibodies against various targets are being developed for the treatment of AMD, which reflects the etiological complexity of the disease. This review provides an overview of 19 potential therapeutic antibodies targeting angiogenesis, the complement system, inflammation or amyloid beta deposition in the eye. It summarizes the immunoglobulin structure, the specific target and study outcomes for each approach. The latter include beneficial results or adverse effects in AMD models and patients. Finally, this article discusses the challenges in the development of antibody-based drugs to treat degenerative processes in the posterior eye. In spite of these difficulties, to date, the following four antibodies have overcome the technical and preclinical hurdles and are being tested in active clinical studies: Lampalizumab, Sonepcizumab, GSK933776 and LFG316. We conclude that, while there are some antibody-based drugs that have made it into clinical practice, a successful transfer from bench to beside is still pending for many promising approaches.

KEYWORDS:

Age-related macular degeneration; Anti-amyloid β; Anti-angiogenic; Anti-complement system; Anti-inflammatory; Clinical studies; Intravitreal; Therapeutic antibody

PMID:
25725263
DOI:
10.1016/j.ejpb.2015.02.020
[Indexed for MEDLINE]

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