Combined drug triads for synergic neuroprotection in retinal degeneration

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Title: Combined drug triads for synergic neuroprotection in retinal degeneration
Authors: Maneu, Victoria | Lax, Pedro | De Diego, Antonio Miguel G. | Cuenca, Nicolás | García, Antonio G.
Research Group/s: Neurobiología del Sistema Visual y Terapia de Enfermedades Neurodegenerativas (NEUROVIS)
Center, Department or Service: Universidad de Alicante. Departamento de Óptica, Farmacología y Anatomía | Universidad de Alicante. Departamento de Fisiología, Genética y Microbiología
Keywords: Retina degeneration | Calcium dyshomeostasis | Oxidative stress | Neuroinflammation | P2X7 receptors | Drug repositioning | Drug combinations | Neuroprotection
Knowledge Area: Farmacología | Fisiología | Biología Celular
Issue Date: 4-Apr-2022
Publisher: Elsevier
Citation: Biomedicine & Pharmacotherapy. 2022, 149: 112911.
Abstract: This review focuses on retina degeneration occurring during glaucoma, age-related macular degeneration (AMD), diabetic retinopathy (DR), and retinitis pigmentosa (RP), and on the potential therapeutic use of triads of repositioned medicines, addressed to distinct but complementary targets, to prevent, delay or stop retina cell death. Although myriad pathogenic mechanisms have been implicated in these disorders, common signaling pathways leading to apoptotic cell death to all of them, and to all neurodegenerative diseases are (i) calcium dyshomeostasis/excitotoxicity; (ii) oxidative stress/mitochondrial dysfunction, and (iii) neuroinflammation/P2X7 receptor activation. From a therapeutic point of view, it is relevant to consider the multitarget approach based on the use of combined medicines acting on complementary pathogenic mechanisms that has been highly successful in the treatment of chronic diseases such as cancer, AIDS, pain, hypertension, Parkinson’s disease, cardiac failure, depression, or the epilepsies as the basic mechanisms of cell death do not differ between the different CNS degenerative diseases. We suggest the multi-target therapy approach could be more effective compared with single-drug treatments. Used at doses lower than standard, these triads may also be safer and more efficient. After the establishment of a proof-of-concept in animal models of retinal degeneration, potential successful preclinical trials of such combinations may eventually drive to test this concept in clinical trials in patients, first to evaluate the safety and efficacy of the drug combinations in humans and then their therapeutic advantages, if any, seeking the prevention and/or the delay of retina degeneration and blindness.
Sponsor: We thank the support received from the EU Horizon 2020 Research and Innovation Program under Maria Slodowska‐Curie, Grant/Award Number: Grant Agreement N. 766124; Fundación Teófilo Hernando; Spanish Ministry of Science and Innovation (FEDER-PID2019-106230RB-I00) and Generalitat Valenciana (IDIFEDER/2017/064, PROMETEO/2021/024).
ISSN: 0753-3322 (Print) | 1950-6007 (Online)
DOI: 10.1016/j.biopha.2022.112911
Language: eng
Type: info:eu-repo/semantics/article
Rights: © 2022 Published by Elsevier Masson SAS. This is an open access article under the CC BY-NC-ND license (
Peer Review: si
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Appears in Collections:Research funded by the EU
INV - NEUROVIS - Artículos de Revistas

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