Dry Age-Related Macular Degeneration
Age-related macular degeneration (AMD) is a degenerative eye disease that upon progression to advanced stages impacts a patient’s sharp, central vision, causing it to become blurry or obstructed. The disease results in difficulty in conducting daily tasks such as reading, driving or recognizing faces. AMD is fairly common, affecting millions of Americans, and is a leading cause of vision loss among individuals 50 or older.
AMD occurs in two forms: dry and wet. Dry AMD is the most common form of the disease, accounting for approximately 80 percent of all AMD cases. It goes along with the formation of drusen (small yellow deposits) beneath the retina, which progressively expand in size and damage the retina over time (intermediate AMD). Upon further progression, cells waste away and die (geographic atrophy) which can cause central blindness.
Dry AMD affects more than 7.5 million Americans and more than 20 million adults in the western world. Treatments for this condition are limited and there are no approved oral therapeutic options.
Over the past decade, an expanding body of scientific research has connected uncontrolled oxidative stress and the damage it causes to photoreceptors and the retinal pigment epithelium to the progression of AMD. These findings have highlighted the down-regulation of lipid peroxidation (LPO), which contributes both to oxidative stress and the buildup of toxic byproducts that drive drusen formation, as a potential therapeutic approach to treating dry AMD.
Docosahexaenoic acid (DHA) is the most prevalent PUFA found within photoreceptors, accounting for approximately 80 percent of all PUFAs in these cells. DHA plays an important role for visual function but due to its inherent instability, DHA also serves as the primary substrate for the pathological LPO process within the retina that is believed to contribute to inflammation and dry AMD.
Retrotope is developing RT011, an isotopically stabilized version of DHA, for the treatment of dry AMD. By replacing natural DHA with the chemically stabilized RT011, Retrotope aims to remove the fuel that drives uncontrolled, disease-causing LPO, without impacting the critical role that DHA plays within the eye. Promising preclinical results have suggested the ability of RT011 to protect retinal cells and preserve photoreceptors in various oxidative stress-related animal models.
The company expects to file an Investigational New Drug (IND) application for RT011 in 2021 and initiate first-in-human clinical studies in dry AMD soon thereafter. Unlike most other dry AMD treatments in development, RT011 is an oral drug, offering key administration advantages.