Phase I NT-501 Ciliary Neurotrophic Factor Implant Trial for Primary Open-Angle Glaucoma

Development of a novel SupraChoroidal-to-Optic-NervE (SCONE) drug delivery system

“…There are no current treatments for ischemic optic neuropathy (Stunkel & Van Stavern, 2018 ) and targeted delivery of neuroprotective agents (e.g. neurotrophic factors (Goldberg et al., 2023 ; Ghasemi et al., 2018 ; Yungher et al., 2017 ; Pease et al., 2009 ; Cen et al., 2007 ), antioxidants, and/or steroids (Stunkel & Van Stavern, 2018 ; Saxena et al., 2014 ; Beck et al., 1992 )) to the optic nerve head may ameliorate axonal loss. And finally, glaucomatous damage occurs at the optic nerve head possibly through neuro-inflammatory (Evangelho et al., 2019 ; Participants LIIoAaGN., 2017; Soto & Howell, 2014 ) or biomechanical insults (Downs & Girkin, 2017 ;Gerberich et al., 2021 ).…”

“…Current ophthalmic delivery methods may include topical eye drops, intravitreal injections (using 30- or 32- gauge hypodermic needles), sub-Tenon’s delivery, and systemic administration – none of which specifically target the optic nerve head. Agents to be delivered could include neuroprotective agents, such as neurotrophic factors (including ciliary neurotrophic factor (Goldberg et al., 2023 ; Ghasemi et al., 2018 ; Yungher et al., 2017 ; Pease et al., 2009 ; Cen et al., 2007 ) and brain derived neurotrophic factor (Harper et al., 2011 ; Heng et al., 2024 )), steroids (corticosteroids (Stunkel & Van Stavern, 2018 ; Saxena et al., 2014 ; Beck et al., 1992 ) and neurosteroids (Ishikawa et al., 2014 ; 2018 ; Izumi et al., 2023 )), antioxidants (Martucci & Nucci, 2019 ; Ekicier Acar et al., 2020 ; Kang et al., 2021 ; Cáceres-Vélez et al., 2022 ), vasoactive drugs (Quigley et al., 2015 ; Mursch-Edlmayr et al., 2021 ; Arora et al., 2022 ; Eghbali et al., 2023 ), viruses for gene therapies (Martin & Quigley, 2004 ; Leaver et al., 2006 ; Cen et al., 2017 ; Yungher et al., 2017 ), or even cell-based therapies (Harper et al., 2011 ; Mead & Tomarev, 2020 ; Coco-Martin et al., 2021 ). Drugs and even gene therapies could be delivered through the smallest gauge cannulas (as small as 41 G (Irigoyen et al., 2022 )) although cell therapies would require larger gauge to allow for internal diameters greater than cell diameters (Amer et al., 2015 ).…”

A Narrative Review of Pharmacotherapy of Glaucoma

“…Encapsulated cell therapy (ECT) with a high-dose ciliary neurotrophic factor-secreting NT-501 implant has completed phase I trials in patients with POAG, and randomized phase II clinical trials are underway [246].…”