BRINT FAMILY TRANSLATIONAL RESEARCH AWARDS

Yvan Arsenijevic – $300,000
Fondation Asile des aveugles, University of Lausanne

“Gene augmentation therapy for FAM161A-associated retinal degeneration: IND-enabling studies towards a Phase I/IIa clinical trial”

Dr. Arsenijevic's team is developing a gene therapy to treat retinitis pigmentosa caused by mutations in the FAM1161A gene.  In this disease, the FAM161A protein is nonfunctional, leading to faulty photoreceptors that progressively deteriorate.  To advance this treatment, he will conduct preliminary, pre-IND-enabling studies, that are necessary for moving toward a clinical trial.

Vadim Arshavsky – $300,000
Duke University

“Gene-Agnostic Therapy for Retinal Degenerations”

Dr. Arshavsky is working to address a problem found in several retinal diseases that affect the function of retinal proteins. In a process called 'proteasomal overload' there are too many misshaped or wrongly directed proteins.  Normally, proteins are broken down or recycled through machinery called proteosomes, but when there's an overload, these machines can't keep up.  To combat this, the team plans to use gene therapy to boost the number of proteosomes in the photoreceptor, helping to reduce the overload and potentially slow down disease progression.

 

William Beltran – $493,565
University of Pennsylvania

“Characterization and mitigation of AAV-induced ocular inflammation”

Dr. Beltran and his team are working to improve the safety of gene therapies that use viral vectors to deliver the therapeutic gene to retinal cells. As more IRD gene therapies move from the preclinical stage in animal models to clinical trials, there is an increasing recognition of the need to better understand gene therapy associated uveitis (inflammation).  This inflammatory response can impede the therapy’s performance and can cause retinal damage.

 

Sylvain Chemtob – $220,650
Research Center of Hopital Maisonneuve-Rosemont

“Therapeutic innovation for ‘dry’ macular degeneration targeting IL-1R modulation”

Dr. Chemtob will advance MU-010, a novel interleukin-1 receptor modulator, for treating geographic atrophy in dry macular degeneration. This innovative treatment aims to reduce harmful inflammation without affecting the immune system, making it safer and more effective than current options.

 

Yuanyuan Chen – $300,000
University of Pittsburgh

“Nuclear speckle rejuvenation to treat retinitis pigmentosa (RP).”

Dr. Chen is working on proof-of-concept of a new approach for treating dominant forms of retinitis pigmentosa (RP).  The team plans to use a drug therapy, specifically a compound called pyrvinium pamoate, to help regulate proteins in photoreceptors. Inside the cell nucleus, there are structures called nuclear speckles that are rich in factors needed for processing pre-messenger RNAs, molecules that are the precursors of proteins. The team believes that by boosting the activity of these nuclear speckles, they could enhance the entire protein regulation pathway. This could potentially reverse the harmful effects of aberrant protein-related neurodegeneration, including RP.

 

David Corey – $402,223
Harvard Medical School

“Development of Mini-Gene Therapy for Usher Syndrome Type 1F Blindness”

Dr. Corey's team is working on a new approach to treat Usher syndrome type 1F, a condition caused by mutations in the PCDH15 gene. The challenge is that this gene is too large to fit into the standard virus vectors (like AAV) that are often used in gene therapy. To overcome this, the team has created smaller versions of the PCDH15 gene, which they call 'mini-genes'. These mini-genes can fit into the AAV vectors. The team will test these mini-PCDH15 constructs in zebrafish, mice, and human retinal organoids (which are like mini 3D models of the retina) to see if this new approach could be a potential treatment for Usher syndrome type 1F.

 

James Hurley – $211,811
University of Washington

“Stimulation of fatty acid oxidation to diminish drusen”

Dr. Hurley is testing a pharmacological strategy to enhance the oxidation of fatty acids in RPE cells to minimize drusen and vision loss.  The accumulation of drusen is one of the hallmarks of dry age-related macular degeneration.  This project seeks to inhibit an enzyme that will slow the biochemical pathway that produces the lipids contained in drusen deposits, thereby reducing its accumulation in the retina, and slowing disease progression.

 

Shigemi Matsuyama – $500,000
Case Western Reserve University

“Prevention of blindness by an orally available cell death inhibitor”

Dr. Matsuyama is currently evaluating a group of compounds known as the M109S series. These compounds are novel inhibitors of a protein called Bax, which exists in all human cells and plays a role in cell death. By blocking Bax protein activity, there is potential to prevent cell death in the retina, particularly in patients with retinitis pigmentosa (RP).

 

Denise Montell – $300,000
University of California, Santa Barbara

“Development of a New Gene Therapy for Autosomal Dominant Retinitis Pigmentosa”

Dr. Montell is pioneering a gene therapy approach to combat retinitis pigmentosa (RP), specifically the autosomal dominant form caused by misfolded rhodopsin protein. By promoting the degradation of misfolded rhodopsin, through overexpression of the ZIP7 gene, Dr. Montell aims to slow retinal degeneration. Additionally, overexpressing the ZIP7 gene—a zinc transporter protein—may relieve cellular stress and prevent photoreceptor cell death in various models of autosomal dominant RP.

Krzysztof Palczewski – $300,000
The Regents of the University of California, Irvine

“Correcting previously untreatable retinal degenerative diseases using twin prime editing”

Dr. Palczewski seeks to advance a novel gene editing technology called twin prime editing for treating a model of Stargardt disease and develop a twin prime editing framework to address other inherited retinal degenerative diseases.

 

Daniel Paull – $296,150
NY STEM CELL FOUNDATION

“Precision drug discovery for dry age-related macular degeneration using large-scale iPSC modeling”

Dr. Paull will develop a precision medicine platform using stem cells from AMD patients to create retinal cells for drug testing. By automating this process and using advanced imaging and AI, he aims to discover new therapeutic targets and accelerate drug discovery for age-related macular degeneration and other retinal diseases.

 

Kathryn Pepple – $300,000
University of Washington

“Evaluating Mitigation Strategies for Intravitreal Viral Vector-Mediated Inflammation across Animal Models”

Dr. Pepple will investigate novel ocular inflammation mitigation strategies. This will be explored through the evaluation of animal model data and by performing detailed immunologic characterization of the non-human primate eyes during ocular inflammation to provide clinical-pathologic correlations and biomarker validation for use in human clinical studies. A robust and evidence-based approach to preventing ocular inflammation following intravitreal AAV-mediated gene therapy is a critical unmet need.

 

Baerbel Rohrer – $300,000
MitoChem Therapeutics

“Targeting FUS for Neuroprotection: a Novel Therapeutic in Retinal Degeneration”

Dr. Rohrer and team will determine if a small molecule (MC16) can extend the lifespan of retinal cells by targeting mitochondria, which produce cellular energy.  The molecule has the potential to significantly decrease the age-dependent and/or stress-dependent movement of a protein and associated mitochondrial dysfunction observed in retinal degeneration.

 

Renee Ryals – $295,985
Casey Eye Institute, Oregon Health & Science University

“Lipid nanoparticle-mediated gene editing for IRD patients harboring peripherin-2 mutations.”

Dr. Ryals will investigate if prime editing delivered by lipid nanoparticles can successfully correct mutations in the PRPH2 gene, which is correlated with certain retinal diseases. Dr. Ryals is first testing her therapies in induced pluripotent stem cells (iPSCs), which she derives from patient blood and differentiates into human retinal organoids. Retinal organoids are three-dimensional structures, which recapitulate the spatial and temporal differentiation of the retina (including the photoreceptors), serving as effective in-vitro models of retinal development.

 

Ashley Winslow – $631,039
Odylia Therapeutics

“AAV- Anc80 Gene Therapy Platform to Treat Vision Loss caused by RPGRIP1 Mutations”

Dr. Winslow is leading the team at Odylia Therapeutics to advance a gene therapy for Leber congenital amaurosis (LCA6) resulting from RPGRIP1 mutations. The therapy (OT-004) employs the Anc80 AAV capsid to deliver a functional RPGRIP1 gene to photoreceptors.  Odylia will carry out vector production for toxicology studies, assess vector biodistribution and transgene expression, and evaluate vector safety in a 90-day toxicology study.

 

Ben Yerxa – $726,909
Opus Genetics

“IND-enabling study to assess the tolerability and efficacy of a mutation independent rhodopsin knockdown and replacement gene therapy in a canine model of RHO-adRP”

Opus Genetics has developed OPGx-RHO, a gene therapy targeting autosomal dominant retinitis pigmentosa (adRP) caused by mutations in RHO. OPGx-RHO works by knocking down both mutated and wild-type alleles of the RHO gene and replacing them with healthy copies. In collaboration with William Beltran from the University of Pennsylvania, they will test this therapy’s effectiveness and safety in a canine model over six months, using advanced imaging techniques and clinical observations.

FREE FAMILY AMD RESEARCH AWARD

Sheldon Rowan – $199,999
Tufts University

“Diet, microbiome, and genetic therapies to target drusenogenic pathways in an atrophic AMD model”

Dr. Rowan and Dr. Singh's laboratories have teamed together to investigate whether lipophagy, a cellular cleanup process to declutter cells, can be enhanced to slow AMD progression. By activating lipophagy using genetic tools, gene therapy, and dietary interventions, the team aims to relieve cellular stress and prevent photoreceptor cell death. Additionally, they’re testing acarbose, an FDA-approved compound with dual benefits—anti-AMD and pro-lipophagy. This work not only advances our understanding of AMD but also offers hope for preserving vision in affected individuals.

 

Glenn Yiu – $200,000
UC Davis Health

“Exploring mechanisms of drusen biogenesis in nonhuman primates using integrative multiomics”

Dr. Yiu and Dr. Chen will study aged rhesus macaques to understand how drusen deposits form in the eye, which are linked to vision loss in AMD. By analyzing gene activity and blood changes, they aim to identify new drug targets and test treatments, potentially leading to better dietary recommendations for AMD patients.

 

Stephen Tsang – $200,000
Columbia University

“ARMS2/HTRA1 in non–cell-autonomous oxidative and anti-inflammatory therapeutic targeting”

Drs. Tsang and Olah will use CRISPR to identify the causative allele of AMD pathologies and investigate the stress signals of microglia (resident immune cells of the eye,) in AMD that might be treatable as part of a therapeutic strategy to reduce AMD-related cell death. They will also explore whether the presence of at least one low-risk ARMS2/HTRA1 allele maintains oxidative, anti-inflammatory, and overall cellular health in microglia.

ALAN LATIES CAREER DEVELOPMENT AWARD PROGRAM
Clinical Research Fellowship Award

Ahmad Al-Moujahed – $65,000
Massachusetts Eye and Ear

“Assessing the Impact of Retinitis Pigmentosa Genotype on the Prevalence and Clinical Features of Cystoid Macular Edema”

Dr. Al-Moujahed will investigate the genetics of Cystoid Macular Edema (CME) in RP patients, to determine which genes are causing their RP and whether these genes are associated with their CME. This may help to better understand the causes of CME, and lead to earlier treatment.

 

Maram Abdalla – $63,075
Oxford University Hospitals NHS Foundation Trust

“Characterization of the smooth zone of retinal autofluorescence in the macula of choroideremia patients as a biomarker for use as an approvable endpoint in a pivotal gene therapy trial.”

Dr. Abdalla will investigate the presence of a 'smooth zone' in patients with choroideremia, hypothesizing it correlates with photoreceptor loss. The smooth zone is a characteristic area visible on retinal imaging that may indicate the stage of retinal degeneration. Dr. Abdalla aims to validate the smooth zone as a biomarker for disease stage and assess its impact on retinal function.

 

Kirk Stephenson – $65,000
University of British Columbia

“Assessment of potential clinical trial endpoints Part 1: For PRPF31-related IRD & Part 2: Finalizing the first PROM for children with IRD”

Dr. Stephenson will study the natural history of vision change in PRPF31-related autosomal dominant RP patients. He will also administer a questionnaire of patient reported outcome measures to children affected with IRDs. These activities will provide valuable information on the impact of IRDs on visual structure and daily life, which are key for the selection of outcome measures in clinical trials.

 

Kirill Zaslavsky – $65,000
Mass Eye and Ear

“Leveraging large cohorts of genetically-characterized individuals to mitigate phenotypic ascertainment bias”

Dr. Zaslavsky will use genetic data and health records from volunteer biobanks to better understand the link between genotype and phenotype in dominant pathogenic variants associated with IRDs. He will reverse search wider data sets by genotype to learn more about the likelihood of known genetic variants causing disease in those with IRDs and the general population.

CAREER DEVELOPMENT AWARD

Jason Miller – $75,000
Kellogg Eye Center, University of Michigan

“Regulation and Role of RPE Beta-Oxidation in AMD-Relevant Pathology”

Dr. Miller will explore the role of retinal pigment epithelium (RPE) and its ability to degrade the toxic fatty deposits known as drusen. Drusen accumulation outside the RPE leads to RPE death, as well as photoreceptor death, and causes central vision loss. Dr. Miller will use a genetically engineered mouse model and dish-grown RPE cells to determine whether RPE’s ability to degrade fat is important in preventing drusen buildup outside the RPE.

 

Boris Rosin – $75,000
University of Pittsburgh

“Harnessing the Central Nervous System in the treatment of Inherited Retinal Dystrophies”

Dr. Rosin will study the changes of the visual pathways and visual circuit plasticity of the central nervous system prior to and following the application of gene therapy in animal models of IRDs, including a mouse model of retinitis pigmentosa.

 

Christopher Toomey – $75,000
Shiley Eye Institute and Viterbi Family Department of Ophthalmology

“Heparan Sulfate and Lipoprotein Interactions in Bruch's Membrane in the Early Stages of AMD”

Dr. Toomey will investigate whether age-related changes in heparan sulfate (HS) contribute to lipoprotein retention in Bruch’s Membrane during early AMD. HS is a kind of sugar molecule found in the Bruch's membrane (thin layer between the retinal pigment epithelium and choroid,) which normally

holds onto important nutrients and proteins, but as we age changes in HS can cause it to hold onto fats, which shouldn’t be there. This can lead to more drusen and worse vision.

 

Robert Hyde – $75,000
University of Illinois-Chicago

“Inner retinal dysfunction in retinitis pigmentosa”

Dr. Hyde is using a novel electroretinography (ERG) protocol in animal models of retinal degeneration to determine whether retinal remodeling leads to aberrant responses in inner retinal neurons that mask responses to a visual stimulus. ERG is a non-invasive means to measure the electrical responses of various cell types in the retina, to assess function. Inner retinal remodeling can cause aberrant inner retinal responses that limit the potential for functional improvement in all therapies that improve photoreceptor function.

 

Debarshi Mustafi, – $75,000
University of Washington

“Deciphering the Missing Heritability in Inherited Retinal Diseases with Targeted Long-Read Genome Sequencing”

Dr. Mustafi is using long-read DNA sequencing technology to identify heritability in cases where standard genetic testing does not provide an answer due to hidden non-coding variants. Autosomal recessive inheritance requires 2 nonworking variants, and in many cases, only 1 or no variants are located in patients with clinical features of an IRD. Dr. Mustafi will analyze cases where only 1 genetic variant of ABCA4 and USH2A patients have been identified through genetic testing and more in-depth mapping of the genome may result in the detection of a second non-coding variant. This data will be used to expand the gene panel testing of IRD patients to look for rare variants currently not included in standard testing.

 

Katherine Uyhazi – $75,000
University of Pennsylvania

“Investigating the heterogeneity of photoreceptor precursor cells for retinal regeneration”

Dr. Uyhazi is seeking to better understand the different stages of photoreceptor precursor cells during development in order to identify the optimal cell type for cell-based therapies, including transplantation. Each novel subpopulation of photoreceptor precursor cells will be tested for their integration into the retina, and if they can increase photoreceptor cell generation.

 

Thomas Mendel – $75,000
The Ohio State University Wexner Medical Center

“Surgical and adjuvant assisted retinal gene therapy”

Dr. Mendel will use a pig model to test a novel gene therapy administration approach that combines both administration on top of the retina (rather than under the retina) with insulin added to the gene therapy medication to accelerate uptake into retinal cells. Dr. Mendel hypothesizes this gene-agnostic approach will limit inflammation and deliver the gene therapy faster without retinal function degradation.

 

Lesley Everett – $100,000
Oregon Health & Science University Casey Eye Institute

“Investigation of the role of TUBGCP4 and TUBGCP6 in the development of the retinal vasculature”

Dr. Everett is discovering  the role of TUBGCP4 and TUBGCP6 in chorioretinopathy and retinal vascular development, and to investigate whether they represent novel therapeutic targets to inhibit new blood vessel growth. This will determine whether TUBGCP4 and TUBGCP6 regulate retinal vascular development in a cell-autonomous manner.

 

Susanne Roosing – $21,764
Radboudumc, Nijmegen, The Netherlands

“Exploring ectopic gene expression as a novel disease mechanism in autosomal dominant retinal disease”

Dr. Roosing’s project aim is to uncover elusive genes that cause IRDs in complex structural variants and chromosomal rearrangements that lead to errors in or wrongly expressed genes in the retina.

 

Thomas Wubben – $75,000
University of Michigan

“Metabolic uncoupling and AMD: assessing the role of PKM2 in the bioenergetic crisis of the outer retina”

Dr. Wubben is developing a fundamental understanding of how photoreceptors metabolic adaptations uncouple the finely tuned metabolic system in dry AMD and aims to reveal the significance of modulating a metabolic target in photoreceptors.

 

Brian Ballios – $75,000
University Health Network

“Controlling the lineage specification and differentiation of photoreceptor progenitors for retinal regeneration”

Dr. Balios' project focuses on developing and controlling the process in which stem cells produce rod and cone photoreceptors.

TED AND ELAINE WELP ENHANCED CAREER DEVELOPMENT AWARD

Ajoy Vincent, – $127,881
University of Toronto and The Hospital for Sick Children, Toronto

“A Transgenic Mouse Model for an Orphan Hereditary Macular Dystrophy”

Dr. Vincent is leveraging a gene discovery resulting in the creation of a new mouse model from an earlier Foundation award to characterize this mouse model, which lacks a key enzyme needed to breakdown fatty acids and is expected to show a reduction in protective Omega-3 fatty acids and buildup of toxic byproducts. He will follow disease progression in the model to understand disease mechanism and to follow a treatment approach using different dietary supplements to improve retinal health and prevent or slow disease progression.

CLINICAL INNOVATION AWARD

Alessia Amato – $98,440
IRCCS Ospedale Pediatrico Bambino Gesù

“Intersession repeatability and longitudinal follow-up in patients with retinitis pigmentosa undergoing full-field two-color dark-adapted perimetry and light-adapted perimetry with an unmodified and commercially available device”

Dr. Amato will address the need for rod-specific endpoints for conducting evaluations and studies of disease progression and therapy efficacy in people with retinitis pigmentosa and related conditions. She will use 2-color dark-adapted perimetry (2cDAP), a test that utilizes red and blue stimuli to evaluate the function of rods and cones. Validation of this method in a large cohort of patients is a critical step before regulatory agencies can accept it as an outcome measure.

 

Artur V. Cideciyan – $100,000
University of Pennsylvania

“Multi-luminance Chromatic Visual Acuity (MLCVA)”

Dr. Cideciyan and his team will completely re-evaluate the photoreceptor origins of visual acuity (VA) measurements in a wide range of inherited retinal disease and disease stages, as well as in intermediate dry AMD. They will develop a multi-luminance chromatic visual acuity (MLCVA) protocol that can be used in the clinic with a combination of commercially available equipment and publicly available tools.

 

Ramiro Maldonado – $100,000
Duke University

“Ultracompact Hand-held Swept-Source Optical Coherence Tomography as a Novel Diagnostic Modality for Early-Onset Retinal Dystrophies.”

Dr. Maldonado is investigating the use of a hand-held OCT to image young pediatric patients, with and without early-onset retinal disease, to establish an ideal protocol for the use of the hand-held system in standard clinical care and clinical trials. The team will also obtain biomarker data related to retinal degeneration, data related to the effect of specific genetic variants, and insights into foveal development using hand-held OCT.

 

Yi-Zhong Wang – $100,000
Retina Foundation of the Southwest

“Deep Learning Assisted Measurements of Retinal Layer Metrics as Biomarkers for Progression in Retinitis Pigmentosa”

Dr. Wang will develop new, more robust deep learning models to predict visual field sensitivity from OCT scans and other types of retinal images.  His team will conduct studies on the relationship between visual field sensitivity and retinal layer metrics from 50 patients with retinitis pigmentosa. The models will be valuable for reducing the variability of outcome measures in inherited retinal disease clinical trials, thereby reducing the number of patients needed, and the duration of trials required, to determine a therapeutic effect.

CLINICAL RESEARCH PROJECTS

Foundation Fighting Blindness Clinical Consortium
“2024 – RUSH2A Natural History Study”

The Foundation's Clinical Consortium is continuing a natural history study to gain a better understanding of how USH2A mutations affect the severity and progression of vision loss. RUSH2A investigators will follow up with study participants to evaluate whether the short-term results – seen in 2 and 4 years – are predictive of long-term progression that regulators may find more clinically relevant.

INDIVIDUAL INVESTIGATOR RESEARCH AWARD

Cell and Molecular Mechanisms

Yu Holly Chen – $100,000
University of Alabama at Birmingham

“Restoring extracellular matrix signaling between Müller glia and photoreceptors for therapies of inherited retinal degeneration”

Dr. Chen is seeking to better understand the role of muller glia (MG) in the early stages of IRDs. She will determine the cause of MG dysfunction in the retina using human-derived mini retinas, assess the negative impact of MG cell dysfunction on photoreceptor development, and explore the feasibility of rescuing photoreceptors by restoring extracellular matrix signaling, which typically helps cells attach and communicate with nearby cells.

 

Frauke Coppieters – $100,000
Ghent University

“Long non-coding RNAs (lncRNAs) as molecular drivers and therapeutics targets of inherited retinal disease”

Dr. Coppieters is using in-house and public data sets to identify IRD-related long non-coding RNAs (lncRNAs) in the retina and retinal pigment epithelium to create a comprehensive catalog of lncRNA with a potential role in IRDs. Long non-coding RNAs are not converted into protein but are involved in regulating gene expression at the right time and place. This project will evaluate the therapeutic potential of selected lncRNAs in inherited retinal disease patient models.

 

David Matthew Gamm – $100,000
University of Wisconsin-Madison

“Elucidating the human MYO7A interactome to improve understanding of Usher syndrome type 1B and develop potency assays”

Dr. Gamm aims to understand the molecular causes of Usher syndrome type 1B (USH1B) and to develop a test to help create and evaluate treatments. His study will focus on how genetic changes in the MYO7A gene affect human retinal organoid-derived photoreceptor cells and aims to confirm the location of the MYO7A protein, identify its protein partners, and create a reliable test for quality control of new therapies.

 

Brian Link – $100,000
Medical College of Wisconsin

“Investigating cell-type specific Myo7A functions and protein interactions using zebrafish”

Dr. Link and his team will uncover the vital roles of MYO7A in various retinal cell types to better understand Usher syndrome type 1B (USH1B). This research team has developed a pioneering zebrafish model that mirrors the retinal degeneration seen in USH1B patients.

 

Jillian Pearring – $100,000
University of Michigan

“Investigate whether sequestering overly active Arl3-GTP can rescue photoreceptor defects in a mouse model of RP2”

Dr. Pearring aims to determine whether gene therapies sequestering overactive Arl3-GTP can restore photoreceptor function, as well as determine the therapeutic window of treatment to restore visual function in an inherited retinal disease mouse model (RP2null) which exhibits overactive Arl3-GTP. This will provide insights into the impact of photoreceptor nuclear mislocalization on retinal health, advance knowledge of RP2 and ARL3 mutation pathobiology, and identify potential therapeutic targets for inherited blindness.

 

Genetic Technologies

Qin Liu – $100,000
Mass Eye and Ear

“Development of precise correction of c.2299delG mutation in the USH2A gene.”

Dr. Liu and her team will investigate the potential for using prime editing to correct the c.2299delG mutation in the USH2A. Traditional gene therapy is difficult due to the large size of the USH2A gene and the cargo capacity of delivery systems (viruses). Prime editing offers a precise method to correct single gene mutations. This research effort will focus on the feasibility of delivering prime editing components via an adeno-associated virus (AAV) to repair this mutation in a humanized mouse model of USH2A disease.

 

Simon Petersen-Jones – $100,000
Michigan State University

“Knock-down and Replacement Therapy for dominant CRX-associated retinopathies”

Dr. Petersen-Jones is testing a gene knock-down strategy for dominant CRX-associated IRDs (autosomal dominant LCA.) A single mutated copy of CRX can cause diseases. This strategy will block the mutated copy of CRX (using a microRNA) and add back a healthy copy of CRX that will be microRNA resistant. MicroRNA are small non-coding RNAs involved in RNA silencing and regulating gene expression. Dr. Petersen-Jones is looking to test this knockdown and replace technique on CRX as a proof of concept that can also be modified for other dominantly inherited diseases.

 

Peter M.J. Quinn – $100,000
University of Pennsylvania

“Prime editing for Peripherin-2 (PRPH2) inherited retinal dystrophies”

Dr. Quinn is testing a prime editing technique for multiple mutations in PRPH2 using patient-derived retinal organoids. Prime editing is a gene editing technique that splices directly at the site of the mutations and switches out a mutated copy of the gene with a healthy copy. Successful completion of this project will establish a preclinical pathway for proof-of-concept for PRPH2 prime editing therapeutics and lay the foundation for the same strategy to be applied to other IRDs.

 

Genetics

Esther Biswas-Fiss – $100,000
University of Delaware

“Deciphering the Impact of ABCA4 Genetic Variants of Unknown Significance in Inherited Retinal Disease Prognosis.”

Dr. Biswas-Fiss will use computational modeling and experiments to determine whether ABCA4 variants of unknown significance (VUSs) lead to ABCA4-related disease. Solving these VUSs cases will improve diagnosis and ensure that relevant individuals are eligible for clinical trials for ABCA4-directed therapies.

 

Manuel Irimia – $100,000
Centre for Genomic Regulation (CRG)

“Identification, validation and modulation of uncharacterized splicing mutations in inherited retinal diseases”

Dr. Irimia is seeking to uncover novel genetic variants that cause splicing misregulation, leading to IRDs. This project aims to identify new variants in IRD genes that change the way the different pieces of a gene are combined together to make a functional protein. Potential variants identified through genetic sequencing will be tested in the lab to see if their presence has a detrimental effect on gene production and retinal cell biology.

 

Novel Medical Therapies

Janet R. Sparrow – $100,000
Columbia University

“Vitamins E, C and Zinc: Therapeutics for ABCA4-disease (STGD1)”

Dr. Sparrow will conduct preclinical (mouse) studies to test the effectiveness of the AREDS antioxidant formula to treat ABCA4-associated disease (Stargardt disease or STGD1). The AREDS2 supplement formula is frequently prescribed for people with age-related macular degeneration. Her team hopes to demonstrate the protective effect of the AREDS2 formula on photoreceptor cell loss, reduce toxic protein accumulation, and reduce the production of toxic compounds.

 

Restorative Therapies

Thomas Reh – $100,000
University of Washington

“Reprogramming human MG to retinal progenitors and neurons”

Dr. Reh is exploring approaches for enabling retinal cells called Müller glia to sprout new photoreceptors. Previous experiments have shown this is possible by delivering a transcription factor known as ascl1. Dr. Reh is now optimizing photoreceptor regeneration in a 3D culture system that more closely resembles the human retina. He is seeking to improve and optimize the viral delivery of a gene expressing ascl1 for moving the approach closer to evaluation in a clinical trial.

 

Melanie Samuel – $100,000
Baylor College of Medicine

“Targeting microglia to prevent retinal neuron loss in inherited retinal degenerations”

Dr. Samuel is attempting to limit the damage done by microglia (clean-up cells,) in the retina by removing signal regulatory protein alpha (SIRPα). SIRPα being removed should slow excessive cleaning activity in the cell-based model and may improve survival of transplanted photoreceptors. This project could potentially lead to a therapeutic approach for slowing vision loss for a broad range of IRDs.

NON-RODENT LARGE ANIMAL AWARD

Martha Neuringer – $64,884
Oregon Health and Science University

“Creation of a Translational Nonhuman Primate Model of Usher Syndrome 1B”

Dr. Neuringer and her team will expand a gene-edited nonhuman primate (NHP) model of Usher Syndrome 1B. The additional Usher 1B animals will allow for studies to determine how closely primates harboring MYO7A mutations resemble human disease and for testing a new type of gene therapy that uses a dual-AAV platform that can facilitate the delivery of the MYO7A gene, which is too large to fit in a single AAV vector.

 

Yannis Paulus – $166,454
Johns Hopkins University

“Development of Rabbit Models of Eyes Shut Homolog-Associated Retinal Degeneration”

Dr. Paulus and his team will develop two rabbit models of EYS each with a common mutation found in patients. (Mutations in EYS are a common cause of RP.) They propose to do so using gene and base editing tools to create two lines of mutant rabbits that will be phenotypically characterized by using non-invasive functional and imaging methods that are already in place in their labs.

 

Simon Petersen-Jones – $167,406
Michigan State University

“Characterization of a large animal Stargardt disease model – suitability for translational therapy trials”

Dr. Petersen-Jones will establish a breeding colony of ABCA4-affected dogs and determine if the disease progression can be accelerated with vitamin A supplementation. The retina of Stargardt disease patients accumulates material called bisretinoid that fluoresces with UV light. As part of the study, Dr. Petersen-Jones will standardize a way of measuring the amount of autofluorescence in affected dogs.  This has the potential to be a new standard monitoring measurement to grade the rate of disease progression in Stargardt disease patients.

 

Bhanu Telugu – $119,955
University of Missouri

“Generation and characterization of a novel porcine model of Choroideremia”

Dr. Telugu is focused on creating a novel porcine model for choroideremia. His study aims to replicate the pathogenesis of human choroideremia by inactivating the CHM gene in pigs. A clinically relevant minipig model will aid in the development of validated, reproducible, safe, and effective treatments for human patients.

 

Erwin van Wijk – $166,789
Radboud University Medical Center Nijmegen

“Generation and characterization of a porcine model for Usher syndrome type 2c”

Dr. van Wijk will generate a multifunctional humanized knockout pig model for Usher syndrome type 2C (USH2C) that can be used for basic and translational research.  A humanized porcine model for USH2C can enable the assessment of therapeutic strategies currently under development. The model will help identify the optimal delivery routes and dosing and can enable toxicological assessment of therapeutic compounds prior to entering clinical trials.

PRPH2 AND ASSOCIATED RETINAL DISEASES AWARD

Frauke Coppieters – $129,309
Ghent University

“Elucidating Disease Heterogeneity and a Novel Therapeutic Approach for PRPH2-related Inherited Retinal Disease”

Dr. Coppieters will investigate why symptoms vary widely among people with PRPH2-related eye diseases. By studying protein levels and genetic factors in patient cells, she aims to understand these differences and test a new treatment approach using antisense oligonucleotides to correct genetic issues, potentially offering new therapeutic options.

 

Muayyad R. Al-Ubaidi – $160,400
University of Houston

“Mutation-independent therapeutic strategy for peripherin 2 associated diseases”

Dr. Al-Ubaidi aims to create a new treatment for diseases linked to the PRPH2 gene by using small RNA molecules to switch off the mutated gene and replace it with a healthy one in animal studies.

 

Andrew Goldberg – $140,255
Oakland University

“Natural history and AAV-mediated interventions for dominant negative and haploinsufficient mouse models of PRPH2-associated disease.”

Dr. Goldberg will conduct a natural history study on two strains of mice with different PRPH2 mutations. One mouse strain has a loss-of-function mutation, meaning there is a mutated copy of the gene that is not working properly and the other healthy copy cannot make up for the loss. The second mouse strain has a dominant negative mutation of the gene, resulting in a protein that interferes with normal function. His team will test whether AAV-mediated delivery of PRPH2 can stop or slow disease progression.  The characterization of the mice to understand how these mutation types affect PRPH2-related disease will be a resource for other researchers developing therapies for this disease.

 

Krzysztof Palczewski – $159,868
The Regents of the University of California, Irvine

“Precision genome editing in humanized mice expressing mutant peripherin-2”

Dr. Palczeski aims to create a mouse carrying the human PRPH2 gene in place of the mouse gene, which will allow researchers to test genome editing therapies for PRPH2-associated retinal diseases.

 

Jason Comander – $166,667
Massachusetts Eye and Ear

“A Comprehensive Approach to Determining the Genetic Causality of PRPH2-Associated Retinal Degeneration”

Dr. Comander will investigate which of the 6000+ genetic changes in the PRPH2 gene cause vision loss. Using advanced cell tests and zebrafish models, he aims to identify problematic gene variants and understand how they lead to retinal degeneration, ultimately improving patient diagnoses and treatments.

 

Yoshikazu Imanishi – $169,257
Indiana University

“Elucidating Pathophysiological Mechanisms and Advancing High-Throughput Drug Discovery in PRPH2-Related Retinal Dystrophies”

Dr. Imanishi will determine how mutations in PRPH2 affect protein trafficking and incorporation into the outer segment of photoreceptors. This will improve our understanding of disease processes and aid in the identification of new therapies. His team will screen small drug-like molecules to find potential treatments and examine how mutations in the PRPH2 gene differently effect rods and cones using frog photoreceptors.

PROGRAM PROJECT AWARD

Audo, Isabelle – $563,080
Fondation Voir et Entendre

“Fighting Usher syndrome type IB blindness: disease pathogenesis and treatment solutions”

Dr. Audo and her team will focus on Usher Syndrome type 1B. With access to a large USH1B patient population, they will define onset, progression and severity of photoreceptors cell death; contributions of rods and cones; and and seek specific biomarkers for Usher disease severity and progression. They will also generate new models (mouse and retinal organoids) to test potential therapies for MYO7A-related retinal organoids) to test potential therapies for MYO7A-related retinal degeneration.

 

Jeremy Kay – $603,500
Duke University

“Defining the underlying causes of retinal degeneration in CRB1 disease”

Dr. Kay and his team hypothesize that loss of cell-cell connections in the outer retina underlies RP-like aspects of CRB1-associated disease, while loss of junctions between embryonic progenitors underlies LCA-like aspects. Dr. Kay's team will use multiple models to identify primary site(s) of damage caused by CRB1 dysfunction, and explore strategies to fix the damage. They will also work to determine whether these cellular features can be imaged in animals and in patients and be used as an endpoint in future clinical trials.

 

Dror Sharon – $501,880
Hadassah-Hebrew University Medical Center

“In vivo retinal RNA editing using the cellular adenosine deaminase acting on RNA (ADAR) enzyme”

Dr. Sharon and his team will advance RNA editing technology to correct specific retinal disease-causing mutations.  By developing and administering novel biological machinery to the retina that uses enzymes called “adenosine deaminase acting on RNA” or ADAR that serves as molecular editors to correct a specific mutation in RNA.  The technique is like gene editing but instead of editing the gene, this technique edits RNA, which is the transcript or message read from the gene to produce protein.

 

Alison Hardcastle – $594,737
UCL Institute of Ophthalmology

“Investigating the novel disease mechanism for autosomal dominant retinitis pigmentosa type 17 and exploring therapeutic approaches”

Dr. Hardcastle and her team aim to unravel the molecular basis of RP17, a form of retinal disease caused by structural genomic variants, a new genomic mechanism leading to autosomal dominant retinitis pigmentosa. Their projects will contribute to the resolution of elusive gene mutations causing retinal diseases, as well as other extraretinal genetic diseases.

 

Alberto Auricchio – $446,000
Fondazione Telethon

“microRNA-based therapy of inherited retinal diseases (RetMir)”

Dr. Auricchio and a team of co-investigators through their program, called “RetMir”, are identifying microRNAs and microRNA antagonists or ‘sponges’ that have a neuroprotective effect on the retina in order to provide a one-fits-all, mutation-independent therapeutic approach for inherited retinal degenerations.

 

Silvia Finnemann – $539,142
Fordham University

“A novel, rationally designed pharmacological approach to countering vision loss in a preclinical model of MERTK-associated Retinitis Pigmentosa”

Dr. Auricchio and a team of co-investigators through their program, called “RetMir”, are identifying microRNAs and microRNA antagonists or ‘sponges’ that have a neuroprotective effect on the retina in order to provide a one-fits-all, mutation-independent therapeutic approach for inherited retinal degenerations.

Research Core Award

 

Kristy Lee – $50,000
University of North Carolina

“Salary support for a biocurator to continue the variant curation effort of the ABCA4 gene through a Variant Curation Expert Panel Protocol that will be deposited into the ClinVar database.”

Dr. Lee will continue the ABCA4 gene curation effort started by the ABCA4 Variant Curation Expert Panel, which is depositing new ABCA4 gene variants into the ClinVar database. This work will help to identify individuals appropriate for clinical trial interventions as well as gene therapy treatment once approved by FDA.

 

Lori Sadler Sullivan – $24,998
UTHealth Houston

“RetNet Curation”

Dr. Sullivan is responsible for the management and curation of the RetNet database. RetNet provides tables of genes and loci causing inherited retinal diseases to the research community.

 

William Beltran – $500,000
University of Pennsylvania

“Penn Large Animal Model Translational & Research Center”

Dr. Beltran and his team are using dog models to accelerate the development and pre-clinical testing of new and effective approaches to treat different forms of IRDs. This program will focus on identifying new canine forms of IRD and establishing how well they recapitulate the equivalent human retinal diseases. Models that are clinically relevant will then be characterized and used to better understand the disease process, with the goal of identifying new therapeutic targets.

 

Shannon Boye – $24,565
University of Florida

“Mouse model of KIZ”

Dr. Boye will develop a mouse model to study a specific type of eye disease called KIZ-associated Retinitis Pigmentosa (RP). She will track how the disease progresses over time and identify the best period for treatment, which will help in testing new therapies in the future.