Research We’re Supporting
Creation and Characterization of A Non-Human Primate USH1B Model
Martha Neuringer, Oregon Health Science University and Casey Eye Institute
This is a 3 year project funded by Save Sight Now. Dr. Neuringer and her colleagues are using the gene-editing technique CRISPR/Cas9 to develop large animal models of Usher syndrome type 1B, which is caused by mutations in the gene MYO7A. Better translational models are urgently needed for USH1B to facilitate understanding pathogenetic processes and test potential therapies. Nonhuman primates best mirror human retina anatomy and function by having a macula and fovea, as well as photoreceptor calyceal processes that are a major site of dysfunction in Usher syndrome but are absent in rodents. As of May 2022, Martha and her team have successfully created an USH1B NHP model that is expressing all three phenotypes associated with Usher syndrome type 1B: 1) balance issues 2) bilateral profound hearing-loss 3) early onset of retinal degeneration. Martha’s program requires sustained funding to care for this new primate - Gema - as well an entire cohort of primates in order to ensure the process is replicable.
Creation of ush1b retinal organoids to develop Critically Needed therapies
Mark Pennesi, Oregon Health Science University and Casey Eye Institute
This is a 1 year pilot program track of work, intended to grow into a larger program. Mark Pennesi and his team will develop translational human retinal organoid models of USH1B retinal degeneration to 1) uncover previously unknown molecular disease mechanisms, 2) determine the optimal window for gene therapy, and 3) optimize therapeutic interventions for USH1B. Resulting therapies will lead to future testing in larger animal models.
Development of gene therapies based on understanding of USH1B pathogenesis
Isabelle Audo, Deniz Dalkara, Aziz El Amraoui, Serge Picaud, Institut de la Vision Paris
This is a large 5 year, multi-track project funded by Save Sight Now and the Foundation Fighting Blindness. This project is designed to bring together basic scientific discoveries as well as innovative therapeutic interventions to ensure timely fulfillment of two main objectives: 1) USH1B genotype-phenotype correlations, disease natural history study (Light4Deaf) and USH1B molecular signatures, and 2) the development of gene therapies based on understanding of USH1B pathogenesis.
Dr. Audo and her team are advancing knowledge about Usher syndrome type 1B from clinical findings, disease mechanisms, and current approaches on gene/protein delivery and therapeutic strategies to prevent or alleviate vision deterioration in USH1B. With access to a large USH1B patient population, they are defining onset, progression, and severity of photoreceptors cell death, contributions of rods and cones involved, and biomarkers for severity and progression. The team will also evaluate CRISPR/Cas9 gene editing as an approach to correcting mutations in the MYO7A gene.
Characterization of Naturally occurring ush1b pig model
Uwe Wolfrum & Kerstin Wolfrum, Wolfrum Lab, Institute of Molecular Physiology, JGU
This a 3 year program funded by Save Sight Now. The Wolfrums have made an incredible discovery of a naturally occurring USH1B pig model and are breeding and supporting an USH1B pig colony in order to study, characterize and establish a porcine model for Usher syndrome type 1B, to later use for testing new therapies.
Dr. Wolfrum is using pigs born with Usher syndrome type 1B (mutations in MYO7A) to characterize disease mechanisms and test potential therapies in the retina. Current Usher syndrome rodent models are not ideal because they don’t exhibit vision loss due to structural differences between rodent and human retinas. Furthermore, the pig eye is closer in size to the human eye, which makes it a better platform for testing potential retinal therapies.