Aptamer in Macular Degeneration Research

The potential of aptamers being the panacea for most of the eye-related disorders is huge. A variety of nucleic-acid-based therapies have been developed against macular degeneration worldwide. As an industry-leading company, Creative Biolabs has established an optimal aptamer development platform and has extensive experience in aptamer application research. We are capable of providing global customers with comprehensive aptamer development services to promote your project success.

Introduction of Macular Degeneration

Age-related macular degeneration (AMD) is the leading cause of severe vision loss among individuals over 50 years of age in the Western world and it is caused by various issues ranging from genetic to environmental factors. This disease is usually associated with the accumulation of undegraded waste around the retinal pigment epithelium, which is produced as a result of the repair and regeneration process of the eye. There are two forms of AMD, namely wet and dry AMD, leading to the central loss of vision. Wet AMD is characterized by the presence of leaky and fragile blood vessels leading to the accumulation of fluids. This results in scars to the macula. In dry AMD there is a loss of photoreceptors and pigmentation in the retinal epithelium. Dry AMD is the more difficult form to treat and drugs targeting the pathophysiology of the disease progression have been designed.

Fig.1 Schematic of the eye with healthy retina, choroid, and retinal pigment epithelium (RPE) cells and effects of AMD. (Rastoin, 2020)

Aptamer in Macular Degeneration Research

The eye is a complex organ with a highly regulated molecular mechanism controlling its functions. Small disparities in the protein target interactions can lead to severe diseases in the eye eventually leading to loss of vision. This sensitive nature of eye disorders demands highly specific, targeted, long-lasting, flexible, and nontoxic therapeutic strategies to overcome these problems at the molecular level. Hence, aptamers form the most appropriate class of molecules suitable for treating eye disorders mainly because of their very high specificities to their target molecules and their nonimmunogenic nature. Also, aptamers are significantly larger than the small molecular therapeutics, hence their retention in the eye is longer. This improved bioavailability and nontoxicity overcome several hurdles that other small molecules or protein-based therapeutics face. Here we show a few of the aptamers that have shown promising results and those that are likely to be investigated extensively in AMD shortly.

1. Anti-VEGF aptamer: Macugen/Pegaptanib

Up to now, only one intravitreal anti-VEGF agent has been approved by the FDA (in 2004): Macugen1, an anti-VEGF RNA aptamer. It has been approved as a drug for use in the treatment of wet AMD. Pegaptanib is an antiangiogenic aptamer that targets VEGF that inhibited the binding of VEGF to endothelial cells in vitro. Pegaptanib had serum stability of more than 18 h in ambient temperatures and hence was found suitable for therapeutic use.

2. Anti-C5 complement aptamer (ARC1905)

ARC1905 showed promising results in animal models and is currently under Phase I clinical trials. Although this aptamer was essentially conceptualized for treatment against dry AMD, it was also successful for wet AMD when used in combination with anti-VEGF therapeutics such as ranibizumab.

3. Anti-PDGF aptamer (E10030)

Although anti-VEGF agents are effective at controlling neovascularisation, there is no regression of the new vessels already formed that are responsible for vision loss. To overcome this hurdle, aptamers that bind to PDGF were developed. E10030 (Fovista^TM) is a PEGylated, 20 F- and 20 OMe-modified 29 nucleotide aptamer. E10030 was successfully trialed in combination with anti-VEGF agents and induced neovascular regression when administered. Studies have shown that AMD treatment with an anti-VEGF agent is more effective when combined with E10030.

Services at Creative Biolabs

Long-time committed to the research of aptamer development and application in therapeutics, Creative Biolabs has built a comprehensive aptamer research system. Our specialists with advanced degrees will customize optimal solutions to meet clients’ every specific requirement, meanwhile, the reliable technology platform will help to provide a top-rated customer experience with one-stop and worry-free services.

The huge potential of aptamer in macular degeneration has aroused researchers’ interest. As a forward-looking CRO company, Creative Biolabs has established an advanced aptamer development platform. We are capable of offering high-quality services to global customers. Please feel free to contact us for more information.

Reference

1. Rastoin, O.; et al. Experimental models in neovascular age related macular degeneration. Int J Mol Sci. 2020, 21(13).

Related Product

• Aptamer in Coagulation Research
• Aptamer in Oncology Research
• Aptamer in Inflammation Research