PulseSight: New Peer-Reviewed Data Highlighting Transferrin’s Therapeutic Potential for Dry AMD
PulseSight Therapeutics welcomed the publication of new scientific data reinforcing the therapeutic promise of transferrin (Tf) for the treatment of dry age-related macular degeneration (AMD).
The study, conducted by scientists from Inserm and Cochin Hospital in Paris in collaboration with PulseSight’s researchers, was published this week in Nature Publishing’s Cell Death & Disease[1]. The findings provide evidence that iron dysregulation is not merely a bystander but a driver of retinal degeneration, particularly during the early stages of geographic atrophy (GA), the advanced form of dry AMD.
Dysregulation of iron homeostasis has long been implicated in retinal diseases, where excess iron contributes to oxidative stress, inflammation, and ferroptosis—forms of cellular damage that accelerate degeneration of the retinal pigment epithelium (RPE) and photoreceptors. These processes are believed to underlie progression from dry AMD to GA.
Transferrin, a naturally occurring glycoprotein, binds and transports iron in a non-toxic form, maintaining iron balance and preventing harmful accumulation in ocular tissues. The published study provides mechanistic insight into how restoring transferrin levels could protect retinal cells from ferroptosis—a form of iron-dependent cell death increasingly recognized as a key contributor to AMD pathology.
Study Findings
In one of the largest analyses of aqueous humor samples from AMD/GA patients to date, researchers identified elevated iron levels and increased transferrin saturation, confirming the presence of iron imbalance in AMD pathology.
Complementary in vitro experiments in human RPE cells revealed that iron overload triggered oxidative stress, mitochondrial damage, inflammation, complement activation, and ferroptosis—all hallmarks of AMD. Exposure to oxidized lipids produced similar disturbances in iron metabolism and cellular stress pathways.
Importantly, transferrin supplementation in these models restored iron homeostasis and significantly reduced oxidative and inflammatory injury, preserving RPE integrity and supporting the therapeutic relevance of targeting iron regulation in AMD/GA.
According to PulseSight, these findings strengthen the scientific foundation of PulseSight’s lead candidate, PST-611, a first-in-class non-viral vectorized therapy delivering a plasmid encoding transferrin directly into the eye. PST-611 is designed to restore iron balance and preserve retinal structure and function in patients with dry AMD and early GA.
Currently in a phase 1 clinical trial, PST-611 aims to demonstrate safety and biological activity, with results expected by early 2026.
“Over the past years, growing evidence has pointed to iron as an important contributor to retinal degeneration in dry AMD,” said Professor Joshua Dunaief, University of Pennsylvania, a member of PulseSight’s Scientific Advisory Board. “Iron can promote oxidative damage and inflammation, both central to disease progression. I am very enthusiastic to see programs such as PST-611 entering clinical testing to demonstrate the value of this target in preserving vision and improving patients’ lives.”
“I congratulate my colleagues on this important publication,” said Thierry Bordet, PhD, Chief Scientific Officer and Chief Operating Officer at PulseSight Therapeutics. “It confirms the role of ferroptosis in AMD/GA, the critical importance of restoring iron homeostasis, and the protective potential of transferrin in this highly disabling disease. At PulseSight, we have designed a unique translational strategy to restore iron balance and prevent ferroptosis. With PST-611, we combine mechanistic relevance, long-lasting efficacy, and a de-risked delivery platform — positioning PST-611 as a potential major therapeutic option for patients with dry AMD/GA.”
Reference
Youale et al., “Transferrin is a drug candidate for the treatment of dry age-related macular degeneration (AMD),” Cell Death & Disease. 16, 692 (2025). PMID: 41053100