Cell Rejuvenation Therapy for Age-related Macular Degeneration

Introduction

Age-related macular degeneration (AMD) is a leading cause of blindness, resulting in loss of vision at the center of the visual field - the macula, due to damage to the retina. The disease, usually affecting older adults (>55), was diagnosed in 2020 in 196 million people worldwide, with an estimated economic toll of $343 billion including $255 billion in direct healthcare costs.

Disease Mechanism

In AMD, photoreceptors and retinal pigmented epithelium (RPE) cells, which underlie the photoreceptors, undergo degeneration. The standard care involves injections of anti-VEGF medicines such as:

1. Ranibizumab (Lucentis)
2. Aflibercept (Eylea)
3. Brolucizumab (Beovu)

These treatments delay disease progression but cannot restore lost vision and have side effects such as bleeding in the eye.

Research Discovery

During an ERC Starting project, the PI discovered a new method that would allow not only delaying the disease but also improving RPE cell function as a treatment for AMD. The proposed approach to rescue RPE cells is rejuvenation by a technique called partial reprogramming.

Our results suggest that the proposed technique is safe and efficient in rejuvenating mouse and human fibroblasts and in improving their function.

Proposed Approach

In the current application, through in vivo studies, we will prepare for implementing our novel approach in our envisioned product “I-SEE”. In “I-SEE”, we will aim to use our discovery of a unique combination of factors that successfully reprogram cells to drive aging RPE cells into rejuvenation and improved function.

Methodology

We will:

1. Calibrate the expression of the reprogramming factors in RPE cells.
2. Test rejuvenation and improved function in AMD mouse models.

Development and Partnerships

IPR and partnerships with clinicians and industry will be developed concomitantly. Our final product, “I-SEE”, is developed based on a PCT patent Application No. 63/210,030, as a cocktail of molecules of mRNA directly applied to the eye, to offer the first AMD treatment that could restore vision.