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Detecting retinal cell stress and apoptosis with DARC: Progression from lab to clinic

Cordeiro, MF; Hill, D; Patel, R; Corazza, P; Maddison, J; Younis, S; (2022) Detecting retinal cell stress and apoptosis with DARC: Progression from lab to clinic. Progress in Retinal and Eye Research , 86 , Article 100976. 10.1016/j.preteyeres.2021.100976. Green open access

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Abstract

DARC (Detection of Apoptosing Retinal Cells) is a retinal imaging technology that has been developed within the last 2 decades from basic laboratory science to Phase 2 clinical trials. It uses ANX776 (fluorescently labelled Annexin A5) to identify stressed and apoptotic cells in the living eye. During its development, DARC has undergone biochemistry optimisation, scale-up and GMP manufacture and extensive preclinical evaluation. Initially tested in preclinical glaucoma and optic neuropathy models, it has also been investigated in Alzheimer, Parkinson's and Diabetic models, and used to assess efficacy of therapies. Progression to clinical trials has not been speedy. Intravenous ANX776 has to date been found to be safe and well-tolerated in 129 patients, including 16 from Phase 1 and 113 from Phase 2. Results on glaucoma and AMD patients have been recently published, and suggest DARC with an AI-aided algorithm can be used to predict disease activity. New analyses of DARC in GA prediction are reported here. Although further studies are needed to validate these findings, it appears there is potential of the technology to be used as a biomarker. Much larger clinical studies will be needed before it can be considered as a diagnostic, although the relatively non-invasive nature of the nasal as opposed to intravenous administration would widen its acceptability in the future as a screening tool. This review describes DARC development and its progression into Phase 2 clinical trials from lab-based research. It discusses hypotheses, potential challenges, and regulatory hurdles in translating technology.

Type: Article
Title: Detecting retinal cell stress and apoptosis with DARC: Progression from lab to clinic
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.preteyeres.2021.100976
Publisher version: https://doi.org/10.1016/j.preteyeres.2021.100976
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Annexin, Apoptosis, Biomarker, Cell stress, DARC, Geographic atrophy, Glaucoma, In vivo, RGC, Retina, Wet AMD
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology
URI: https://discovery.ucl.ac.uk/id/eprint/10131806
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