Anti-Angiogenic and Anti-Scarring Dual Action of an Anti-Fibroblast Growth Factor 2 Aptamer in Animal Models of Retinal Disease
| Autor: | Yoshikazu Nakamura, Toshiaki Nishihata, Satoshi Futakawa, Yusaku Matsuda, Hirotaka Imai, Masatoshi Fujiwara, Yusuf Ali, Kazumasa Akita, Robert B. Bhisitkul, Yosuke Nonaka |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
genetic structures FGF2 VEGF inhibitors Angiogenesis AMD Fibroblast growth factor Article Pathogenesis angiogenesis 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Fibrosis Drug Discovery Medicine business.industry fibrosis lcsh:RM1-950 aptamer Macular degeneration medicine.disease eye diseases Pathophysiology Vascular endothelial growth factor lcsh:Therapeutics. Pharmacology 030104 developmental biology Choroidal neovascularization chemistry 030220 oncology & carcinogenesis Cancer research Molecular Medicine sense organs medicine.symptom business |
| Zdroj: | Molecular Therapy: Nucleic Acids, Vol 17, Iss, Pp 819-828 (2019) Molecular Therapy. Nucleic Acids |
| ISSN: | 2162-2531 |
| Popis: | Currently approved therapies for age-related macular degeneration (AMD) are inhibitors against vascular endothelial growth factor (VEGF), which is a major contributor to the pathogenesis of neovascular AMD (nAMD). Intravitreal injections of anti-VEGF drugs have shown dramatic visual benefits for AMD patients. However, a significant portion of AMD patients exhibit an incomplete response to therapy and, over the extended management course, can lose vision, with the formation of submacular fibrosis as one risk factor. We investigated a novel target for AMD treatments, fibroblast growth factor 2 (FGF2), which has been implicated in the pathophysiology of both angiogenesis and fibrosis in a variety of tissue and organ systems. The anti-FGF2 aptamer, RBM-007, was examined for treatment of nAMD in animal models. In in vivo studies conducted in mice and rats, RBM-007 was able to inhibit FGF2-induced angiogenesis, laser-induced choroidal neovascularization (CNV), and CNV with fibrosis. Pharmacokinetic studies of RBM-007 in the rabbit vitreous revealed high and relatively long-lasting profiles that are superior to other approved anti-VEGF drugs. The anti-angiogenic and anti-scarring dual action of RBM-007 holds promise as an additive or alternative therapy to anti-VEGF treatments for nAMD. Keywords: FGF2, aptamer, AMD, VEGF inhibitors, angiogenesis, fibrosis |
| Databáze: | OpenAIRE |
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