Along with glaucoma and the rare disease, Leber’s hereditary optic neuropathy, Rohan also mentioned geographic atrophy as an indication in which clinicians had expressed keen interest in testing PYC-001.
Geographic atrophy (GA) is the progressive, irreversible, advanced form of dry age-related macular degeneration (AMD). Geographic atrophy affects millions of people worldwide, including about 1 million people in the United States, where the disease is responsible for ~20% of cases of legal blindness. In comparison, ADPKD is estimated to impact a US patient population of 500,000.
The hallmark sign of GA—sharply demarcated atrophic lesions due to loss of photoreceptors, RPE, and choriocapillaris—which first appears in the outer retina, causes progressive visual impairment by expanding toward the fovea and eventually leading to irreversible vision loss. (1)
Strong experimental evidence from studies of human donors with AMD supports the hypothesis that a bioenergetics crisis in the retinal pigment epithelium (RPE) underlies the pathobiology of AMD and that targeting the mitochondria (the cells’ primary source of energy) in the RPE may provide the most efficacious intervention strategy. (2)
The energy needs of the retina are very high - in a similar range to the brain. Retinal ganglion cells (RGC) possess an exceedingly active metabolism and are particularly vulnerable to energy insufficiency. (2)
In ADOA patient-derived models, PYC-001 has demonstrated the capacity to restore RGC bioenergetics in a mutation agnostic manner. Hence the question, might PYC-001 be capable of meaningfully impacting other eye diseases (such as glaucoma and geographic atrophy) believed to be driven by a bioenergetics deficit?
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Although the FDA approved last year the first two therapies for the treatment of geographic atrophy, a large unmet need still remains. While these treatments, delivered by intravitreal injection every one to two months, have been shown in clinical trials to reduce lesions and slow progression of the disease by 14-20%, they can have severe side effects and have not been shown to have any effect on vision. (3)
(1)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10408405/#:~:text=Researchers have reported about 1,by using multimodal imaging techniques.
(2)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5989860/
(3)
https://www.aao.org/eye-health/tips-prevention/syfovre-izervay-geographic-atrophy-amd-macular-deg
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