Abstract: Age-related macular degeneration (AMD) is a leading cause of blindness worldwide. AMD most commonly affects older individuals and is characterized by irreversible degeneration of the retinal pigment epithelium and neurosensory retina. Currently, there are limited treatment options for dry AMD outside of lifestyle modification and nutrient supplementation. Risuteganib [Luminate (ALG-1001), Allegro Ophthalmics, CA, USA] is an intravitreally administered inhibitor of integrin heterodimers αVβ3, αVβ5, α5β1, and αMβ2. It is currently undergoing clinical trials for the treatment of dry AMD and diabetic macular edema (DME). Preclinical studies have shown that risuteganib has an effect on the pathways for angiogenesis, inflammation, and vascular permeability. Ongoing clinical trials have had promising results showing improvements in patient best corrected visual acuity (BCVA) and reduced central macular thickness measured by optical coherence tomography (OCT). There is a pressing need for treatments for dry AMD and while risuteganib appears to have a potential benefit for patients, more data are needed before one can truly evaluate its efficacy. This narrative review provides a concise summary of the most up to date data regarding the proposed mechanism of action of risuteganib in the treatment of nonexudative AMD and DME as well as the results from recent phase 1 and phase 2 clinical trials.
Abstract: The purpose of this article is to review current literature and data regarding treatment options for age-related macular degeneration (AMD) related to mitochondrial therapy. This article considers the presence of flavoprotein fluorescence as a potential biomarker to test the effectiveness of the treatments. We focus primarily on two major mitochondrial targets, nuclear factor erythroid 2-related factor (NFE2L2) and PGC-1α, that function in controlling the production and effects of reactive oxidative species (ROS) directly in the mitochondria. PU-91 is an FDA approved drug that directly targets and upregulates PGC-1α in AMD cybrid cell lines. Although neither NFE2L2 nor PGC1-α have yet been tested in clinical trials, their effects have been studied in rodent models and offer promising results. MTP-131, or elamipretide?, and metformin are two drugs in phase II clinical trials that focus on the treatment of advanced, non-exudative AMD. MTP-131 functions by associating with cardiolipin (CL) whereas metformin targets adenosine-monophosphate protein kinase (AMPK) in the mitochondria. The current results of their clinical trials are elucidated in this article. The molecular targets and drugs reviewed in this article show promising results in the treatment of AMD. These targets can be further pursued to improve and refine treatment practices of this diagnosis.
