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Editors Selection IGR 23-4

Medical Treatment: Neuroprotection

Keith Martin

Comment by Keith Martin on:

108604 Phase I NT-501 Ciliary Neurotrophic Factor Implant Trial for Primary Open-Angle Glaucoma: Safety, Neuroprotection, and Neuroenhancement, Goldberg JL; Beykin G; Satterfield KR et al., Ophthalmology science, 2023; 3: 100298

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A significant minority of people with glaucoma continue to lose vision despite therapies that lower intraocular pressure. Thus, there remains an unmet clinical need for treatments that protect or enhance visual function. Ciliary neurotrophic factor (CNTF) has been shown to protect retinal function in multiple pre-clinical models of retinal disease. The NT-501 device is an intravitreal implant that contains encapsulated, immortalized human RPE-derived cells engineered for long-term release of CNTF into the human eye. The device has previously been shown to increase retinal thickness in early phase clinical trials in retinitis pigmentosa and AMD. In the current study by Goldberg et al., the NT-501 device was implanted in 11 eyes of 11 patients with glaucoma in a Phase 1 safety study where participants were followed for 18 months. The implant was reported to be safe and well-tolerated in eyes with POAG, with no devices having to be removed during the study.

The investigators reported that some subjects who received the implant demonstrated both structural and functional improvements suggesting biological activity. However, as the investigators point out in their discussion, this was a small, non-randomized study, and the baseline level of disease was significantly worse in the implanted eyes than in the fellow eyes. This might potentially bias the results toward observing improvements or less worsening of structural and functional measures in the study eyes. Thus, it remains to be seen if this strategy can mediate consistent neuroprotection or neuroenhancement in human glaucoma.

It remains to be seen if this strategy can mediate consistent neuroprotection or neuroenhancement in human glaucoma

However, the encouraging safety data has supported the premise for a randomized phase II clinical trial of single and dual NT-501 CNTF implants in patients with POAG, which is now underway. The results are awaited with great interest.

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