Challenging Paradigms in AMD: Gregory S. Hageman, PhD


The executive director of the Steele Center for Translational Medicine at the Moran Eye Center discussed his team’s research in the role of HTRA1.

“There are a number of programs out there that are directing approaches to decrease [HTRA1] levels with antibodies... So, I've gotten calls from those folks who are thinking, ‘oh man, what have we done’, but more of the calls are from the pharma companies that say, ‘oh, all these other big companies are [downregulating]. We'd like to investigate upregulating now.”

HTRA1 had previously been thought to contribute to the development of age-related macular degeneration (AMD), with multiple studies currently ongoing investigating the downregulation of HTRA1 as a therapeutic target. However, recent research from the John A. Moran Eye Center at the University of Utah has elucidated the true role of HTRA1 and another important gene in AMD, ARMS2.

GeneTherapyLive spoke with Brandi. L Williams, PhD, research director, and Gregory S. Hageman, PhD, executive director, Steele Center for Translational Medicine, both from the John A. Moran Eye Center, to learn more about the implications of their findings that HTRA1 has a protective effect on AMD as opposed to contributing to an increased risk of AMD.

Williams and Hageman detail the culmination of 15 years of research in the paper they recently published in PNAS. They also discussed the trials investigating HTRA1 as a therapeutic target.

Williams BL, Seager NA, Gardiner JD, et al. Chromosome 10q26–driven age-related macular degeneration is associated with reduced levels of HTRA1 in human retinal pigment epithelium. PNAS. 2021;118(30) e2103617118. doi:10.1073/pnas.2103617118
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