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An international natural history study for patients with RP caused by EYS mutations

Researchers led by Prof. Mark Pennesi M.D., Ph.D., based at the Ophthalmic Genetics Oregon Health & Science University, Portland, USA, has launched a new international natural history study, called “Rate of Progression in EYS Related Retinal Degeneration (Pro-EYS)”.  The study will be funded by the Foundation Fighting Blindness, and will involve 25 centres across the globe including Belgium, France, Germany, Poland, the Netherlands, the UK, Canada, Brazil, Israel and the United States.


“Eyes shut homolog”, or “EYS” (OMIM: 612424) is a relatively recent genetic lesion causing retinitis pigmentosa (RP), initially reported by two independent groups in 2008.  The gene is a human ortholog of Drosophila “eyes shut” (eys), also known as “Spacemaker” (spam). At present, mutations in EYS are estimated to account approximately ~5% to 35% of European and Asian autosomal recessive retinitis pigmentosa cases however,  there are additional sporadic reports with autosomal recessive cone-rod dystrophy (CRD). The  EYS gene is located on chromosome 6p12 (RP25 locus), spanning over 2 Mb of DNA comprising 44 exons coding a protein of 350kDa.  The protein is located in the outer segments and connecting cilium / transition zone of both rod and cone photoreceptors, playing an important role in retinal morphogenesis and architecture.


The purpose of the research project is to characterize the natural history of disease progression in patients with EYS mutations in order to accelerate the development of outcome measures for clinical trials.  The clinical study is now registered at the identifying goals of the natural history, including:

(i) describe the natural history of retinal degeneration in patients with biallelic mutations in the EYS gene;

(ii) identify sensitive structural and functional outcome measures to use for future multicenter clinical trials in EYS-related retinal degeneration;

(iii) identify well-defined subpopulations for future clinical trials of investigative treatments for EYS-related retinal degeneration.


Commenting on the launch of the project, Dr. Todd Durham, Ph.D., vice president of clinical development and outcomes research at the Foundation, stated: “The findings from this natural history study will be published and widely disseminated so that we can share what we learn with therapy developers from around the world.  Our goal is to boost and accelerate EYS therapy development for all commercial and academic researchers. One way we do this is to make de-identified data from the study accessible to researchers who can use it to design clinical trials. This study is a significant undertaking and we are grateful to the investigators, reading centers, laboratories, genetics experts, and study participants who make this possible.”