Matrix metalloproteinase-3 (MMP-3)-mediated gene therapy for glaucoma

O'Callaghan J, Delaney C, O'Connor M, van Batenburg-Sherwood J, Schicht M, Lütjen-Drecoll E, Hudson N, Ni Dhubhghaill S, Humphries P, Stanley C, Keravala A, Chalberg T, Lawrence MS, Campbell M (2023)

Publication Type: Journal article

Publication year: 2023

Journal

Science Advances American Association for the Advancement of Science

Book Volume: 9

Pages Range: eadf6537-

Journal Issue: 16

DOI: 10.1126/sciadv.adf6537

Abstract

Approximately 80 million people globally are affected by glaucoma, with a projected increase to over 110 million by 2040. Substantial issues surrounding patient compliance remain with topical eye drops, and up to 10% of patients become treatment resistant, putting them at risk of permanent vision loss. The major risk factor for glaucoma is elevated intraocular pressure, which is regulated by the balance between the secretion of aqueous humor and the resistance to its flow across the conventional outflow pathway. Here, we show that adeno-associated virus 9 (AAV9)-mediated expression of matrix metalloproteinase-3 (MMP-3) can increase outflow in two murine models of glaucoma and in nonhuman primates. We show that long-term AAV9 transduction of the corneal endothelium in the nonhuman primate is safe and well tolerated. Last, MMP-3 increases outflow in donor human eyes. Collectively, our data suggest that glaucoma can be readily treated with gene therapy-based methods, paving the way for deployment in clinical trials.

Authors with CRIS profile

Martin Schicht Lehrstuhl für Funktionelle und Klinische Anatomie Elke Lütjen-Drecoll Lehrstuhl für Funktionelle und Klinische Anatomie

Involved external institutions

Trinity College Dublin IE Ireland (IE) Imperial College London / The Imperial College of Science, Technology and Medicine GB United Kingdom (GB) Hospital Network Antwerp / Ziekenhuis Netwerk Antwerpen (ZNA) BE Belgium (BE)

How to cite

APA:

O'Callaghan, J., Delaney, C., O'Connor, M., van Batenburg-Sherwood, J., Schicht, M., Lütjen-Drecoll, E.,... Campbell, M. (2023). Matrix metalloproteinase-3 (MMP-3)-mediated gene therapy for glaucoma. Science Advances, 9(16), eadf6537-. https://dx.doi.org/10.1126/sciadv.adf6537

MLA:

O'Callaghan, Jeffrey, et al. "Matrix metalloproteinase-3 (MMP-3)-mediated gene therapy for glaucoma." Science Advances 9.16 (2023): eadf6537-.

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