Repurposing Dimethyl Fumarate Targeting Nrf2 to Slow Down the Growth of Areas of Geographic Atrophy
Abstract
1. Introduction
2. Methods
3. Results
3.1. The Direct and Indirect Effects of Oxidative Stress in GA
3.2. Nrf2, a Potential Important Molecular Target for the Treatment of Patients with GA
3.3. Compounds Activating Nrf2 Translocation Are Beneficial Against Retinal Degeneration
3.4. Repurposing Tecfidera™, Whose DMF, Its Active Principle, Is a NRF2 Activator, for the Treatment of GA
3.5. Description of a Clinical Trial Evaluating the Efficacy of Tecfidera™ Repurposed for the Treatment of Patients with GA
- Area of GA determined 1/ by FAF and 2/ by Fundus Photography.
- Macular GA determined 1/ by FAF and 2/ by Fundus Photography.
- Total Drusen Area (determined by FAF).
- Best Corrected visual Acuity (BCVA) (absolute values).
- Contrast Sensitivity determined using the Pelli–Robson Chart.
- Number of scotomatous points (determined by micro-perimetry).
- Mean retinal sensitivity (determined by micro-perimetry).
- Macular choroidal and retinal thickness.
- The percentage of participants with Improved, Stabilized, or worsened BCVA determined using the ETDRS chart.
- Number of scotomatous points and mean retinal sensitivity (determined by micro-perimetry).
- Changes in the NIHVFQ25 questionnaire.
- Changes in blood immune cell populations’ percentage, plasma CRP concentration, plasma SOD activity levels, MDA levels and ROS levels, and plasma cytokines concentration will be determined at 6, 12 and 24 months compared to baseline at Day 0.
4. Conclusions and Perspective
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
References
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Compound | Reported Effects Relevant for AMD Physiopathology | Reference(s) |
---|---|---|
Quercetin | Protects RPE cells from apoptosis and reduces inflammation induced by cigarette smoke extracts in vitro. | [71,72] |
Quercetagetin + lutein/zeaxanthin combination | Reduces photo-oxidative damage induced with LEDs in vivo in rats. | [73] |
Lutein and zeaxanthin | Reduce oxidative stress by inducing the expression of antioxidant enzymes in vivo. | [74,75,76] |
AREDS/AREDS2 oral supplements containing lutein/zeaxanthin | Reduce the speed of progression of GA towards the macula in vivo in humans. | [77] |
Compound K (a metabolite of ginseng) | Preserves the ARPE-19 cell line against oxidative stress induced by H2O2 exposure. Induces the expression of the antioxidant enzyme complex in vitro. | [78] |
Itaconate | Reduces inflammation and oxidative stress in dendritic cells, macrophages/microglia and the T cell line in vitro. | [83,84] |
Dimethyl-itaconate (DMI) | Reduces inflammation and oxidative stress in dendritic cells, macrophages/microglia and the T cell line in vitro. | [83,84] |
4-Octyl itaconate (4-OI) | Reduces inflammation and oxidative stress in dendritic cells, macrophages/microglia and the T cell line in vitro. Reduces the expression of IL-6, IL-8, and MCP-1 and of malondialdehyde and of ROS induced by Angiotensin-II in human primary RPE cells in vitro. | [83,84,85] |
1-[2-cyano-3-,12-dioxooleana-1,9(11) -dien-28-oyl] imidazole (CDDO-Im) | Induces the synthesis of phase II antioxidative enzymes. Reduces the accumulation of complement and inflammatory cells recruitment in the subretinal space during aging in vivo. | [63,64] |
TatNrf2mer (an AAV delivered cell penetrating peptide) | Reduces photoreceptor loss, preserves visual functions and diminishes inflammation induced by sodium iodate (NaIO3) in vivo. | [88] |
17beta-Estradiol | Suppress light induced retinal degeneration in rats in vivo. | [89] |
Monomethyl fumarate (MMF) | Protects retinal integrity, reduces photoreceptors apoptosis, reduces retinal inflammation and restores ERG amplitudes in vivo in a blue-light illumination model. | [96,97,98] |
Dimethyl fumarate (DMF) (precursor of MMF) | Reduces cytokines production by microglia, reduces microglia’s neurotoxicity and protects cortical neurons in vitro. | [93,94] |
Induces antioxidant enzymes production and protects RPE cells from oxidative stress induced by tert-butylhydroperoxide (tBH) in vitro. | [69,95] |
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Camelo, S. Repurposing Dimethyl Fumarate Targeting Nrf2 to Slow Down the Growth of Areas of Geographic Atrophy. Int. J. Mol. Sci. 2025, 26, 6112. https://doi.org/10.3390/ijms26136112
Camelo S. Repurposing Dimethyl Fumarate Targeting Nrf2 to Slow Down the Growth of Areas of Geographic Atrophy. International Journal of Molecular Sciences. 2025; 26(13):6112. https://doi.org/10.3390/ijms26136112
Chicago/Turabian StyleCamelo, Serge. 2025. "Repurposing Dimethyl Fumarate Targeting Nrf2 to Slow Down the Growth of Areas of Geographic Atrophy" International Journal of Molecular Sciences 26, no. 13: 6112. https://doi.org/10.3390/ijms26136112
APA StyleCamelo, S. (2025). Repurposing Dimethyl Fumarate Targeting Nrf2 to Slow Down the Growth of Areas of Geographic Atrophy. International Journal of Molecular Sciences, 26(13), 6112. https://doi.org/10.3390/ijms26136112