PulseSight Therapeutics Presents Promising Data on PST-611 for Dry AMD/Geographic Atrophy
核心洞察
PulseSight Therapeutics (搜索) presented data on PST-611, a non-viral vectorized therapy for dry age-related macular degeneration (搜索) (AMD) and geographic atrophy (搜索) (GA), at the EVER Congress 2024.
PST-611 expresses human transferrin (搜索), restoring iron homeostasis in retinal cells, which mitigates oxidative stress, inflammation, and ferroptosis associated with AMD.
Safety data supports PST-611 administration via a minimally invasive electrotransfection system, targeting the ciliary muscle, showing promise for clinical development.
PulseSight Therapeutics (搜索) SAS presented new data on its lead program PST-611, a DNA plasmid expressing human transferrin (搜索), for the treatment of dry age-related macular degeneration (搜索) (AMD) and geographic atrophy (搜索) (GA) at the European Association for Vision and Eye Research (EVER) Congress 2024. The data supports the potential of PST-611 to restore iron homeostasis and protect retinal cells in patients with advanced dry AMD.
Addressing Iron Imbalance in AMD
AMD, affecting 200 million people worldwide, often involves disrupted iron homeostasis, leading to an excess of free iron and subsequent inflammation, oxidative stress, and cell death. In advanced stages, dry AMD progresses to geographic atrophy (搜索) (GA), characterized by the atrophy of the retinal pigment epithelium (RPE), photoreceptors, and choriocapillaris, resulting in progressive vision loss. PST-611 is designed to address this imbalance by coding for human transferrin (搜索), a potent iron chelator.
Transferrin's Role in Restoring Retinal Health
Dr. Thierry Bordet, CSO of PulseSight, presented data from a retrospective study indicating higher levels of free iron and increased transferrin (搜索) saturation in dry AMD patients compared to controls. Further data showed that transferrin supplementation in iRPE cells exposed to high iron concentrations restored iron homeostasis and rescued RPE cells from oxidative stress, mitochondrial damage, inflammation, complement activation, and ferroptosis, preserving their integrity.
Minimally Invasive Delivery and Safety Profile
To overcome the challenge of delivering drugs to the back of the eye, PulseSight is utilizing a minimally invasive electrotransfection system. Dr. Karine Bigot, Head of Pharmacology & Toxicology at PulseSight, presented a poster demonstrating the safety of PST-611 when administered to the ciliary muscle using this system.
Clinical Development Plans
PulseSight is planning to submit a Phase I clinical trial authorization (CTA) by the end of 2024, with a Phase II proof-of-concept study to follow by the end of 2027. According to Dr. Bordet, restoring normal iron homeostasis with transferrin (搜索) mitigates toxic effects and protects retinal cells, potentially slowing GA lesion growth and improving patient's visual function. He also noted the favorable safety profile of PST-611 as a novel non-viral vectorized gene therapy delivered through electroporation.