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- Free Family Foundation AMD Award
- Career Development Awards
- Clinical Research Fellowship Awards
- Clinical Innovation Award
- Individual Investigator Research Awards
- Program Project Awards
- Research Core: Non-Rodent Large Animal Awards
- Translational Research Acceleration Program Awards
- FFB Supported Workshop
FREE FAMILY FOUNDATION AMD AWARD
Stephen Tsang, MD, PhD and Marta Olah, PhD - $600,000
“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 brain,) 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.
CAREER DEVELOPMENT AWARDS
Robert Hyde, MD, PhD - $375,000
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, MD, PhD - $375,000
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 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, MD, PhD - $375,000
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.
CLINICAL RESEARCH FELLOWSHIP AWARDS
Anfisa Ayalon, MD - $65,000
University of Pittsburgh
“Spectral properties of ERG oscillatory potentials in hereditary retinal dystrophies prior to and following the application of gene therapy employing a novel gel-based AAV vector delivery system.”
Dr. Ayalon will study the spectral properties of ERG oscillatory potentials (OPs) in hereditary retinal dystrophies and will evaluate if the frequency domain of OPs can be used as a new diagnostic tool. Dr. Ayalon will also investigate if the gel-based epiretinal AAV vector delivery system has a better retinal cell transduction efficiency than subretinal and intravitreal injections.
Thales Guimaraes, MD - $65,000
Moorfields Eye Hospital NHS Foundation Trust
“Exploring Retinal Structure and Function in Patients with CDH23-associated Usher syndrome.”
Dr. Guimaraes will study patients previously confirmed, via genetic testing, with Usher syndrome type I due to CDH23. Our aim is to perform several tests, using state-of-the-art cutting-edge technology, to analyze the structure and function of the retina in a group of 25 patients within a period of 12 months. This will be the first study to systematically assess detailed photoreceptor structure and correlate it with measures of visual sensitivity in CDH23 Usher type 1.
CLINICAL INNOVATION AWARD
Ramiro Maldonado, MD - $300,000
“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.
INDIVIDUAL INVESTIGATOR RESEARCH AWARD
Esther Biswas-Fiss, MS, PhD - $300,000
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 are critical to meet inclusion criteria in a clinical trial for ABCA4 therapies.
Yu Holly Chen, PhD - $300,000
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, MSc, PhD - $300,000
“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 RNA (lncRNA) in the retina and retinal pigment epithelium to create a comprehensive catalog of lncRNA with a potential role in IRDs. Long non-coding RNA does not convert code into protein but are part of 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.
Manuel Irimia, PhD - $300,000
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.
Simon Petersen-Jones, DVetMed, PhD, DVOphthal, DECVO - $300,000
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 bad copy of CRX can cause diseases. This strategy will stop the bad copy of CRX and add back a good copy of CRX using artificial microRNA that will also be microRNA resistant. MicroRNA are small non-coding RNA 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 Quinn, PhD - $300,000
“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 bad copy of the gene with a good 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.
Thomas Reh, PhD - $300,000
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, PhD - $300,000
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.
PROGRAM PROJECT AWARDS
Silvia Finnemann, PhD - $2,472,518
“A novel, rationally designed pharmacological approach to countering vision loss in a preclinical model of MERTK-associated Retinitis Pigmentosa.”
Dr. Finnemann and her team will determine if an early-onset inflammatory response in the RPE precedes photoreceptor degeneration. If successful in uncovering this novel disease pathway, a therapeutic strategy testing anti-inflammatories for MERTK-associated RP is proposed that could prevent or significantly delay retinal degeneration.
Dror Sharon, PhD - $2,500,000
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.
RESEARCH CORE: NON-RODENT LARGE ANIMAL AWARDS
Martha Neuringer, PhD - $499,844
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 to use for initial tests of gene therapy. The expanded animal models of Usher 1B will allow for studies to determine how closely primates harboring Usher 1B genetic variation resembles the human disease and use the model to test 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.
Simon Petersen-Jones, DVetMed, PhD, DVOphthal, DECVO - $500,000
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 the grade the rate of disease progression.
TRANSLATIONAL RESEARCH ACCELERATION PROGRAM AWARDS
Krzysztof Palczewski, PhD, MS - $900,000
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.
François Paquet-Durand, PhD - $989,000
Mireca Medicines GmbH
“Towards the clinical translation of mutation-independent treatment for hereditary retinal degeneration using the inhibitory cGMP analogue CN03 "BlockPKG".”
Mireca Medicines/Graybug seeks to advance the preclinical development of the cGMP-signaling targeting drug CN03, and a delivery system, toward concept testing in humans. This signaling molecule can over-activate the enzyme protein kinase G (PKG). Light-sensitive cell loss can be triggered by excess levels of the signaling molecule cGMP. This group previously discovered that inhibition of this enzyme can bring the rapid degeneration of light-sensitive cells to a halt and thereby preserving retinal structure and function.
Kathryn Pepple, MD, PhD - $900,000
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, PhD - $900,000
“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, PhD - $887,955
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 derives induced pluripotent stem cells (iPSCs) from patient blood and differentiate them into human retinal organoids for therapeutic testing. 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.
FFB SUPPORTED WORKSHOP
Cold Spring Harbor Laboratory - $5,000
Cold Spring Harbor Laboratory
“2023 Cold Spring Harbor Lab – Vision: A Platform for Linking Circuits, Behavior & Perception.”
Vision: A Platform for Linking Circuits, Behavior & Perception to be held in Long Island, NY between June 16-July 1, 2013. The purpose of this course is to bring together students and faculty for in-depth and high level discussions of modern approaches for probing how specific cell types and circuits give rise to defined categories of visual perception and behavior. It is also designed to address novel strategies aimed at overcoming diseases that compromise visual function.