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Investigational Agents in Development for the Treatment of Geographic Atrophy Secondary to Age-Related Macular Degeneration

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Abstract

Geographic atrophy (GA) is an advanced form of age-related macular degeneration, a late-onset, complex, genetic degenerative disease of the retina. Multiple environmental and genetic factors have been implicated in the development of GA, a pathology ultimately defined by loss of photoreceptors and the underlying retinal pigment epithelium and choriocapillaris. The personal burden of GA has been documented to have a substantial negative impact on quality of life, with progressive and cumulative loss of visual function each year. Currently, there are no treatments to prevent or slow the development or progression of GA. Multiple genetic and histopathologic studies have implicated dysregulation of the complement cascade in GA pathogenesis, leading to the development of several investigational pharmaceuticals targeting key factors in this inflammatory pathway. Several other biochemical pathways have also been implicated in GA development and progression, such as mitochondrial components, mediators of apoptosis and molecules involved in extracellular matrix remodeling, many of which are also being investigated for their potential value as therapeutic targets for GA treatment. Recent advancements in our understanding of GA pathogenesis and the progression of multiple potential therapeutics into later-stage human clinical trials hold great promise for a clinically effective therapeutic for patients with GA to emerge within the near future.

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  1. Retina Consultants of Texas, Retina Consultants of America, 4460 Bissonnet St., Suite 200, Bellaire, Texas, 77401, United States

    Hannah J. Yu & Charles C. Wykoff

  2. Blanton Eye Institute, Houston Methodist Hospital, Houston, TX, USA

    Charles C. Wykoff

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Hannah Yu has no conflicts of interest that are directly relevant to the content of this article. Charles C. Wykoff has provided consulting services to Allergan, Apellis, Genentech, Gyroscope, IVERIC Bio, Merck, NGM Biopharmaceuticals, Novartis, OccuRx, ONL Therapeutics, and Roche and has received research support from Apellis, Gemini Therapeutics, Genentech, Gyroscope, IONIS Pharmaceutical, IVERIC Bio, LMRI, Neurotech Pharmaceuticals, NGM Biopharmaceuticals, and Novartis.

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Charles C. Wykoff was responsible for the study conceptualization. Hannah J. Yu was responsible for the literature search and data analysis and writing and preparing the original draft. Hannah J. Yu and Charles C. Wykoff reviewed and edited the manuscript. All authors read and approved the final manuscript.

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Yu, H.J., Wykoff, C.C. Investigational Agents in Development for the Treatment of Geographic Atrophy Secondary to Age-Related Macular Degeneration. BioDrugs 35, 303–323 (2021). https://doi.org/10.1007/s40259-021-00481-y

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