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

PARIS, Oct. 14, 2025 (GLOBE NEWSWIRE) -- PulseSight Therapeutics, a clinical stage ophthalmology biotech company developing disruptive non-viral vectorized therapies with minimally-invasive delivery technology welcomes the publication of new data reinforcing interest in transferrin (Tf) as a drug candidate for the treatment of dry age-related macular degeneration (AMD), in a study performed by scientists from Inserm and Cochin Hospital in Paris, in collaboration with PulseSight’s scientists.

Dysregulation of iron homeostasis plays a crucial role in retinal diseases, contributing 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 Geographic Atrophy (GA). Tf, an endogenous glycoprotein, regulates iron homeostasis by binding and transporting iron in a non-toxic form, preventing harmful accumulation.

The study sought to provide mechanistic insights into the role of iron dysregulation into dry AMD/Geographic Atrophy (GA) and how transferrin could prevent ferroptosis, a form of iron-dependent cell death increasingly recognized as a key contributor to AMD pathology.

The peer-reviewed publication this week in Nature Publishing Cell Death & Disease⁽¹⁾ provides compelling support for the hypothesis that iron dysregulation is not merely a bystander, but a potential driver of dry AMD, especially in the early geographic atrophy (GA) stage

These clinical data confirm PulseSight’s therapeutic strategy in developing PST-611, an innovative first-in-class non-viral vectorized therapy 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. Now well progressed in a phase I clinical trial, results are expected by early 2026.

AMD is the leading cause of central vision loss in the elderly, affecting 200 million people worldwide. AMD's pathogenesis is complex, and the disease still represents a high unmet need.

Study detail

The scientists explored iron-transferrin imbalance in one of the largest aqueous humor datasets to date from dry AMD/GA patients and age-matched controls patients. The study confirmed elevated iron levels and increased transferrin saturation in aqueous humors of AMD patients, providing clinical confirmation of iron dysregulation in the disease.

In addition, the team conducted complementary in vitro experiments demonstrating that, in human RPE cells, iron overload triggered oxidative stress, mitochondrial damage, inflammation, complement activation, and ferroptosis - key hallmarks of AMD. Similarly, exposure of RPE cells to oxidized lipids induced similar changes in iron homeostasis and downstream cascades.

In these stressed conditions, TF supplementation restored iron balance and significantly reduced oxidative and inflammatory damage in RPE cells, preserving the integrity of the epithelial structure and further reinforcing the therapeutic relevance of iron modulation in GA — still an underexplored treatment avenue.

Welcoming these new insights, Professor Joshua Dunaief, University of Pennsylvania, an expert and pioneer in proposing iron involvement in retinal degeneration, and member of PulseSight’s Scientific Advisory Board, said: “Over the past years, growing evidence has pointed to iron as an important contributor to retinal degeneration in dry AMD. Iron can promote oxidative damage and inflammation, both of which are central in disease progression. I am very enthusiastic to see programs such as PST-611, based on this approach, entering clinic, and demonstrate the value of this target for treatments that could preserve vision and improve patients’ lives.”

Thierry Bordet, Ph.D., CSO/COO of PulseSight Therapeutics, added, “I congratulate my colleagues on this important publication. 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’ve designed a unique translational strategy to restore iron homeostasis 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 option for patients with dry AMD/GA.”

^1. Youale et al., “Transferrin is a drug candidate for the treatment of dry age-related macular degeneration (AMD),” Cell Death & Dis, 16, 692 (2025). PMID: 41053100

Media contact
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About age-related macular degeneration (AMD)

AMD develops with aging. It is a disease with progressive, painless loss of central vision with a strong burden on patients’ everyday life, impacting their ability to read, recognize faces and see objects, and is ultimately leading to irreversible central vision loss. Dry AMD is the most common form of AMD, progressing through successive stages into the late form of dry AMD also called geographic atrophy (GA). Wet AMD is a less common type of late AMD causing faster vision loss. Any stage of dry AMD can turn into wet AMD. In all its forms, AMD represents a compelling unmet need for more effective and durable treatment options, with a large and growing market, estimated to reach $27.5 Billion by 2031.

About PST-611 for GA

PST-611 encodes the human transferrin protein, a crucial regulator of iron homeostasis and holds the potential to effectively address key pathological mechanisms in dry AMD/GA, whilst requiring re-treatment only every four to six months. This program entered a Phase I clinical trial (PST-611-CT1) in France in 2025.

About PulseSight Therapeutics

PulseSight is clinical-stage biotech company committed to developing disruptive non-viral vectorized therapies with minimally-invasive delivery technology to protect and improve the vision of patients with retinal disease with a focus on age-related macular degeneration (AMD) including wet AMD and geographic atrophy (GA) secondary to dry AMD.

Already clinically validated for its safety and sustained activity, PulseSight’s technology platform delivers DNA plasmids encoding therapeutic proteins into the ciliary muscle using an electro-transfection system. The ciliary muscle cells act as biofactories, expressing therapeutic proteins that reach the retina with high distribution, providing a safe and long-lasting treatment for major eye diseases.

Based in Paris, France the PulseSight’s investors are Pureos Bioventures, ND Capital and Korea Investment Partners (KIP).

For more information visit www.PulseSightTherapeutics.com

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