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.
