Research supports that iron dysregulation may drive AMD

A new study supports the hypothesis that iron dysregulation may be a driver of dry age-related macular degeneration (AMD). This could be especially true in the early stage of geographic atrophy (GA).

According to the research, the dysregulation of iron homeostasis contributes to “oxidative stress, inflammation, and ferroptosis, key processes that drive the degeneration of the retinal pigment epithelium (RPE) and photoreceptors and the progression from dry AMD to GA.”¹ Therefore, transferrin (Tf), which is described as “an endogenous glycoprotein, regulates iron homeostasis by binding and transporting iron in a non-toxic form, preventing harmful accumulation,”¹ may be a potential drug candidate to combat AMD and GA.

The study was published in Nature Publishing Cell Death & Disease. In this publication, the investigators “aimed to confirm iron imbalance in a larger cohort of AMD patients and assess its correlation with disease stage.”² The results confirmed that patients with AMD “had significantly higher levels of total iron in the aqueous humor (AH) than did age-matched patients without AMD.”² Spectral-domain optical coherence tomography (SD-OCT) was used to visualize and analyze the classification of atrophy in the patients who participated in the research.

In the discussion portion of the publication, the investigators “observed that TF can reduce intracellular iron levels in RPE cells, potentially mitigating iron-induced cellular damage. Consequently, ocular transferrin supplementation may offer a potential therapeutic approach to help mitigate RPE damage and loss, which could contribute to delaying the conversion of AMD to GA or slowing GA progression.” The researchers also noted that “Larger studies with a greater number of patients in each subgroup, possibly stratified by GA lesion size, are needed to strengthen these findings and determine whether the iron‒TF balance in AH could serve as a biomarker for GA progression.”²

The research was conducted by scientists from Inserm and Cochin Hospital in Paris, in collaboration with scientists from PulseSight Therapeutics. PulseSight is currently developing a pharmaceutical candidate, PST-611, that “delivers a plasmid encoding transferrin into the eye with the aim of restoring iron balance and preserve retinal structure and function in dry AMD/GA.”¹ According to the press release, phase 1 results from the clinical trial are expected early in 2026.¹ 

In July of 2025, PulseSight dosed the first patient in a phase 1 clinical trial of PST-611 for the treatment of age-related macular degeneration (AMD) and geographic atrophy (GA).³ This study is designed to establish the safety profile for the therapeutic candidate as well as the maximal tolerated dose.³

References:

1. Peer Reviewed Publication Provides Evidence for Iron Dysregulation as a Driver of Dry AMD/GA and the Potential of Transferrin to Restore Iron Balance, Reinforcing PulseSight’s Therapeutic Strategy for PST-611. PulseSight Therapeutics S.A.S. News Release. October 14, 2025. Accessed October 27, 2025. https://finance.yahoo.com/news/peer-reviewed-publication-provides-evidence-070000975.html

2. Youale, J., Bigot, K., Jaworski, T. Transferrin is a drug candidate for the treatment of dry age-related macular degeneration (AMD). Cell Death Dis 16, 692 (2025). https://doi.org/10.1038/s41419-025-07950-0

3. Filkins, K. PulseSight doses first patient in PST-611-CT1. Ophthalmology Times. July 9, 2025. Accessed October 27, 2025. https://www.ophthalmologytimes.com/view/pulsesight-doses-first-patient-in-pst-611-ct1