Foundation Awarded 21 New Grants in FY2021 Totaling More than $14.2 Million

During its fiscal year 2021 (July 1, 2020 – June 30, 2021), the Foundation added 21 new research projects to its portfolio, with awards ranging from early-stage lab research efforts to translational studies for advancing emerging therapies toward clinical trials.

“We are excited to fund a wide range of therapeutic approaches to address the entire spectrum of inherited retinal diseases that affect people of all ages and backgrounds around the world,” said Ben Yerxa, PhD, chief executive officer at the Foundation. “Our new grants and entire research portfolio of nearly 100 projects include gene- and mutation-specific therapies as well as gene-agnostic approaches for helping people regardless of their genetic profile.”

New FY2021 grants included:

• advancement of a drug for Usher syndrome type 3A toward a clinical trial;
• development of a retinitis pigmentosa treatment by re-purposing an FDA-approved therapy for inflammation;
• and advancement of RNA therapies for Stargardt disease toward a clinical trial.

Research grants are selected after a rigorous review process conducted by the Foundation’s Scientific Advisory Board, which is comprised of more than 50 of the world’s leading retinal scientists and clinicians.

New Grants

Development of a Dry AMD Gene Therapy
Bärbel Rohrer, PhD
Medical University of South Carolina
Translational Research Acceleration Program – $342,389

Dr. Rohrer is conducting an animal study of a gene therapy designed to selectively deliver a component of complement factor H (CFH) to temper the overactive innate immune system in age-related macular degeneration. The approach is designed to mitigate retinal degeneration caused by the immune response, targeting the damage where it is most likely to occur.

Advancing a Pharmaceutical Therapy for Retinitis Pigmentosa
Paul Yang, MD, PhD
Oregon Health & Science University
Translational Research Acceleration Program – $900,000

Dr. Yang is evaluating the drug mycophenolate as a therapy for multiple forms of retinitis pigmentosa and related conditions. Already approved by the FDA for inflammatory conditions, mycophenolate has been shown to reduce the accumulation of a molecule called cyclic guanosine monophosphate (cGMP). While cGMP is an important messenger molecule for converting light into electrical signals in the retina, too much of it is toxic and causes retinal degeneration. 

Advancing Small-Molecule for Usher Syndrome 3A (USH3A) in Preparation for Clinical Trial
Mahdi Farhan, MD
Usher 3 Initiative
Translational Research Acceleration Program – $999,700

Dr. Farhan is completing pre-IND toxicity studies to advance a novel small-molecule therapy for USH3A into a Phase 1 clinical trial. The emerging drug works by stabilizing the misfolded USH3A protein (clarin-1) and enabling it to better move to its target location in retinal cells, thereby striving to preserve structure and function.

Enabling the Retina to Generate New Photoreceptors
Tom Reh, PhD
University of Washington
Translational Research Acceleration Program – $874,690

Dr. Reh is developing a process to enable the human retina to grow its own new photoreceptors. Thus far, he has used a small molecule to sprout photoreceptors from Muller glia in mice. The TRAP project is for evaluating the approach in a large animal.

Development of a Cross-Cutting Gene Therapy for Retinitis Pigmentosa
Stephen Tsang, MD, PhD
Columbia University
Translational Research Acceleration Program – $300,000

Dr. Tsang is developing a gene therapy to increase aerobic glycolysis – a process that generates energy -- in cone photoreceptors of those affected by retinitis pigmentosa. He believes the approach may preserve cones for RP patients and would do so independent of the mutated gene causing the disease.

Development of RNA Therapies for Stargardt Disease
Rob Collin, PhD
Radboud University
Translational Research Acceleration Program – $1,414,167

Dr. Collin is developing antisense oligonucleotides (AON) – tiny pieces of DNA – to mask splicing mutations in ABCA4, the affected gene in people with Stargardt disease. The AONs target mutations in RNA, the genetic messages used to build proteins that are necessary for a cell’s health and proper functioning.

Restoring Dormant Retinal Cell Function 
Hendrik Scholl, MD
Institute of Molecular and Clinical Ophthalmology Basel
Translational Research Acceleration Program – $600,000

Dr. Scholl is developing an optogenetic therapy to restore function to dormant cone photoreceptor cells for potentially a broad range of inherited retinal diseases. Cones are responsible for high-acuity, daytime vision, and in a certain percentage of patients, remain in a dormant state. This effort will perform late-stage preclinical studies that are required to start the first-in-human cone-based optogenetic vision restoration clinical trial. This optogenetic therapy produces a protein that makes dormant cone cells sensitive to light.  

MicroRNA-based Therapy for Inherited Retinal Diseases (RetMir)
Alberto Auricchio, MD
Fondazione Telethon
Program Project Award – $2,500,000

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

Automated Software for Analysis of Adaptive Optics Scanning Optical Coherence Tomography Images
Sina Farsiu, PhD
Duke University
Individual Investigator Research Award – $300,000

Dr. Farsiu is developing fully automated computational methods and software to quantify photoreceptors captured in three-dimensional images using adaptive optics scanning optical coherence tomography, a high-resolution imaging modality. He will integrate the final algorithms into a free and easy-to-use software package.

Application of Deep Machine Learning for Identifying Structural and Functional Deficits in Retinitis Pigmentosa
Yi-Zhong Wang, PhD
Retina Foundation of the Southwest
Individual Investigator Research Award – $300,000

Dr. Wang is developing a method using deep machine learning of spectral domain optical coherence tomography (SD-OCT) images to automatically and efficiently quantify the area of the photoreceptor outer segments and transition zone.  Quantifying the size of these features helps to evaluate a patient’s disease progression and response to investigational treatments.

Precision Functional Genomics for Modeling Pathogenesis of Age-Related Macular Degeneration
Martin Pera, PhD
Patsy Nishina, PhD
The Jackson Laboratory
Free Family AMD Research Award – $578,213

Dr. Pera and Dr. Patsy Nishina are creating models of age-related macular degeneration to investigate a potential cellular pathway that may be critical for developing AMD and to assess AMD genetic causes. They are using a precision medicine approach to generate multiple strains of mouse stem cell-derived retinal pigment epithelial cells that are deficient in a known genetic risk factor for AMD called TIMP3. Based on this outcome, they will then determine if they can predict the consequences of these mutations in the development of disease.

Design of a Novel Antisense Oligonucleotide Therapy for Inherited Retinal Diseases
Frauke Coppieters, PhD
Ghent University
Individual Investigator Research Award – $290,000

Dr. Coppieters' goal is to design and validate a novel, mutation-independent antisense oligonucleotide (AON) therapy which will target specific parts of the genome that control retinal RNA expression and, ultimately, protein production for potentially treating a broad range of inherited retinal diseases.

Targeting Tribbles Homolog 3 Protein for Slowing Retinal Degeneration
Marina Gorbatyuk, PhD
University of Alabama Birmingham
Individual Investigator Research Award – $299,338

Dr. Gorbatyuk is using a multipronged approach to test the hypothesis that TRIB3 inhibition, or reduction of TRIB3 activity, will be neuroprotective to the degenerating retina, regardless of the underlying genetic cause. Her project will include evaluation of an FDA-approved drug for reducing TRIB3 activity.

Gene Editing Approaches for the Treatment of Inherited Retinal Diseases
Qin Liu, PhD
Mass Eye and Ear
Individual Investigator Research Award – $300,000

Dr. Liu is developing gene editing strategies for the treatment of retinitis pigmentosa caused by mutations in RP1, the third most common dominant RP gene. This approach is applicable for other types of autosomal dominant RP as well as other inherited retinal diseases with autosomal dominant inheritance.

Generation and Characterization of Swine Models of Usher Syndrome Type 3A
Astra Dinculescu, PhD
University of Florida
Individual Investigator Research Award – $300,000

Dr. Dinculescu is developing an animal model that recapitulates aspects of human USH3A, thus allowing for the execution of experiments to not only study the pathobiology of the disease but also to provide an in vivo system for the testing of potential therapeutics.

Vitamin A Supplementation to Alleviate Night Vision Impairment in Choroideremia Patients
Oleg Alekseev, MD, PhD
Duke University
Career Development Award – $65,000

Dr. Alekseev is investigating the use of vitamin A to improve night and peripheral vision in choroideremia patients. He will also study potential visual function outcome measures for use in choroideremia clinical trials.

Controlling Differentiation of Photoreceptor Progenitors for Retinal Regeneration
Brian Ballios, MD, PhD
University of Toronto
Career Development Award – $375,000

Dr. Ballios is focusing on developing and controlling the process in which stem cells produce rod and cone photoreceptors. He is striving to produce populations of cells that are better at engrafting and restoring function to diseased retinas.

Development and Validation of Visual Function Outcome Assessments for Inherited Retinal Diseases
Maximillian Pfau, PhD
Institute of Molecular and Clinical Ophthalmology Basel (IOB)
Career Development Award – $373,963

Dr. Pfau is developing highly sensitive visual function assessments to document the therapeutic benefits of potential therapies for individuals with inherited retinal diseases. Among his goals, he is establishing and validating artificial intelligence-enhanced fundus-controlled perimetry (microperimetry) testing with a focus on Stargardt disease and Usher syndrome type 2A.

Exploring Ectopic Gene Expression as a Novel Disease Mechanism in Autosomal Dominant Retinal Disease
Susanne Roosing, PhD
Radboud University Medical Center
Career Development Award – $374,999

Dr. Roosing’s project aim is to uncover elusive genes that cause inherited retinal diseases caused by complex structural variants or chromosomal rearrangements that lead to errors in or wrongly expressed genes in the retina.

Harnessing the Central Nervous System in the Treatment of Inherited Retinal Dystrophies
Boris Rosin, MD, PhD
University of Pittsburgh
Career Development Award – $375,000

Dr. Rosin is studying the changes in visual pathways and visual circuit plasticity of the central nervous system prior to and following the application of gene therapy in animal models of inherited retinal diseases, including a mouse model of retinitis pigmentosa. The approach has the potential to lead to better gene and cell therapies for IRDs by maximizing the potential for vision restoration.

Penn Large Animal Translational and Research Center – $2.4 Million
William Beltran, VMD, PhD
School of Veterinary Medicine-University of Pennsylvania

The PENN Large Animal Model Translational and Research Center plays a critical role in bridging basic science and the testing of new therapies in clinically relevant canine models by supporting the research conducted by inherited retinal disease investigators affiliated with the facility and Foundation Fighting Blindness-sponsored scientists from other institutions. The grant is focusing on therapy development and evaluation of canine models for a number of IRDs and will include studies to prepare for clinical trials for Best disease and retinitis pigmentosa gene therapies.