Targeted therapy in age-related macular degeneration (AMD)
Keywordsage-related macular degeneration, gene therapy, VEGF, genetic vectors
Introduction and purpose:
Age-related macular degeneration (AMD) is a major cause of blindness in highly developed countries, with blindness frequency of 8.7%. This article is a review of the latest therapeutic options for AMD.
A brief description of the state of knowledge:
AMD is a multifactorial disease which etiology is not completely understood. Its development is affected by disorders at the cellular level, environmental and genetic factors. Intraocular injections of anti-VEGF agents are currently considered as the basis of AMD neovascular treatment. In the search for better and better therapeutic agents, the effects of administration of bevacizumab and ranizumab were tested. Many clinical studies confirm long-term and effective improvement in patients' vision after using the above-mentioned drugs, indicating that the initial response to treatment and the persistence of the therapeutic effect is individually variable and may be associated with genotypic difference. Another promising alternative to AMD treatment is the use of specific viral vectors that transfer substances slowing down the disease into the vitreous. Another method of gene therapy is the use of HIF transcription factors (hypoxia-induced factors), for now, the research is performed on animal models. Patients with dry AMD also have a chance for successful treatment. Examined gene therapy in dry form of AMD, including retinal surgery combined with viral vector injection, is in I/II phase study in Great Britain.
Looking at the number of blindness cases in highly developed countries caused by AMD, every effort should be made to introduce effective treatment that at least inhibits disease progression. Undoubtedly, more research is needed to confirm the efficacy and long-term safety of AMD.
Mammadzada P, Corredoira PM, André H. The role of hypoxia-inducible factors in neovascular age-related macular degeneration: a gene therapy perspective. Cell Mol Life Sci. 2020 Mar;77(5):819-833.
DeAngelis MM, Owen LA, Morrison MA, Morgan DJ, Li M, Shakoor A, Vitale A, Iyengar S, Stambolian D, Kim IK, Farrer LA. Genetics of age-related macular degeneration (AMD). Hum Mol Genet. 2017 Aug 1;26(R1):R45-R50. doi: 10.1093/hmg/ddx228. Erratum in: Hum Mol Genet. 2017 Oct 1;26(R2):R246. PMID: 28854576; PMCID: PMC5886461.
Nashine S, Cohen P, Chwa M et.al. Humanin G (HNG) protects age-related macular degeneration (AMD) transmitochondrial ARPE-19 cybrids from mitochondrial and cellular damage. Cell Death Dis. 2017 Jul 20;8(7):e2951.
Hagstrom SA, Ying GS, Pauer GJ, Huang J, Maguire MG, Martin DF; CATT Research Group. Endothelial PAS domain-containing protein 1 (EPAS1) gene polymorphisms and response to anti-VEGF therapy in the comparison of AMD treatments trials (CATT). Ophthalmology. 2014 Aug;121(8):1663-4.e1. doi: 10.1016/j.ophtha.2014.02.025. Epub 2014 May 9. PMID: 24813631; PMCID: PMC4122574.
Zhao L1, Grob S, Avery R Kimura A, Pieramici D, Lee J, Rabena M, Ortiz S, Quach J, Cao G, Luo H, Zhang M, Pei M, Song Y, Tornambe P, Goldbaum M, Ferreyra H, Kozak I, Zhang K. Common variant in VEGFA and response to anti-VEGF therapy for neovascular age-related macular degeneration. Curr Mol Med. 2013 Jul;13(6):929-34.
Park UC, Shin JY, McCarthy LC, Kim SJ, Park JH, Chung H, Yu HG. Pharmacogenetic associations with long-term response to anti-vascular endothelial growth factor treatment in neovascular AMD patients. Mol Vis. 2014 Dec 19;20:1680-94. eCollection 2014.
Grunin M, Beykin G, Rahmani E, Schweiger R, Barel G, Hagbi-Levi S, Elbaz-Hayoun S, Rinsky B, Ganiel M, Carmi S, Halperin E, Chowers I. Association of a Variant in VWA3A with Response to Anti-Vascular Endothelial Growth Factor Treatment in Neovascular AMD. Invest Ophthalmol Vis Sci. 2020 Feb 7;61(2):48. doi: 10.1167/iovs.61.2.48.
Hagstrom SA, Ying GS, Maguire MG, Martin DF; CATT Research Group, Gibson J, Lotery A, Chakravarthy U; IVAN Study Investigators. VEGFR2 Gene Polymorphisms and Response to Anti-Vascular Endothelial Growth Factor Therapy in Age-Related Macular Degeneration. Ophthalmology. 2015 Aug;122(8):1563-8. doi: 10.1016/j.ophtha.2015.04.024. Epub 2015 May 28.
Campochiaro PA, Lauer AK, Sohn EH, Mir TA, Naylor S, Anderton MC, Kelleher M, Harrop R, Ellis S, Mitrophanous KA. Lentiviral Vector Gene Transfer of Endostatin/Angiostatin for Macular Degeneration (GEM) Study. Hum Gene Ther. 2017 Jan;28(1):99-111. doi: 10.1089/hum.2016.117. Epub 2016 Sep 26.
Ibuki M, Shoda C, Miwa Y i wsp. Lactoferrin Has a Therapeutic Effect via HIF Inhibition in a Murine Model of Choroidal Neovascularization. Front Pharmacol. 2020 Feb 28;11:174.
Holmgaard A, Alsing S, Askou AL i wsp. CRISPR Gene Therapy of the Eye: Targeted Knockout of Vegfa in Mouse Retina by Lentiviral Delivery. Methods Mol Biol. 2019;1961:307-328.
Liu J, Tian Z, Li J i wsp. Associations of IL-8 gene polymorphisms and IL-8 levels with predisposition to age-related macular degeneration: a meta-analysis. Aging Clin Exp Res. 2020 Mar 10.
Gyroscope Therapeutics, Stevenage Bio-Science Catalyst, FOCUS study, GB. https://www.gyroscopetx.com/gene-therapies/ (dostęp: 23.03.2020).
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