Foundation Fighting Blindness to Fund Nine New Research Grants
July 28, 2011 - The Foundation Fighting Blindness has announced funding for nine new 3-year grants in support of a wide range of innovative retinal research projects including the development of: enhanced genetic screening strategies, new gene therapies, vision-preserving drugs, and advanced retinal imaging techniques.The grants were evaluated through a rigorous multistep process that included comprehensive review and scoring from the Foundation’s Scientific Advisory Board. The Foundation originally received 72 letters of intent from the research community, and requested 34 full applications from the pool.
Stephen Rose, Ph.D. chief research officer of the Foundation says that a number of strong projects did not get funded, because of revenue limitations. “We had to leave a number of high quality proposals on the table,” he says. “Our scientific knowledge and research technologies are advancing at a remarkable rate. Our challenge is generating the revenue to leverage them into treatments and cures.”
Below are summaries of the newly funded grants:
Correcting Errors in the Translation of Genetic Messages — In about 12 percent of all retinal degenerative diseases, vision loss is caused by the premature termination of the translation of critical genetic messages. Dr. Uwe Wolfrum, of Johannes Gutenberg University in Mainz, Germany, is evaluating a drug called PTC124, which corrects these translation errors in an animal model of Usher syndrome. The drug has already shown some effectiveness in clinical trials for Duchene muscular dystrophy and cystic fibrosis, both of which are devastating conditions caused by these reading errors. He plans to position PTC124 for future evaluation in a clinical trial for retinal degenerations. Click here for more information.
Increasing the Delivery Capacity of Gene Therapies (two grants) — Adeno-associated viruses (AAVs) are manmade viruses that are being used successfully in clinical trials and lab studies to deliver therapeutic genes to treat retinal diseases. However, in some cases, the size of the gene exceeds the delivery capacity of the AAV. Dr. Luk Vandenberghe, of the University of Pennsylvania, and Dr. David Schaffer, of the University of California, Berkeley, have both received grants to evaluate multiple approaches to increase the delivery capacity of AAVs, which will be helpful in treating Stargardt disease and certain forms of retinitis pigmentosa (RP) and Usher syndrome (the leading cause of combined deafness and blindness) — conditions which are caused by variations in relatively large genes.
Gene Therapy for Autosomal Dominant Retinitis Pigmentosa — Drs. Alfred Lewin and William Hauswirth of the University of Florida will develop a gene therapy for people affected by autosomal dominant retinitis pigmentosa (adRP) caused by variations in the Rhodopsin gene. A challenge in creating a gene therapy for adRP is that, in addition to delivery of a healthy gene, the bad gene needs to be turned off. In some cases of adRP, the researchers demonstrated that through a one-step process they can simply override the bad gene with a healthy gene. In other cases, they will have to use a two-step process — “knocking down” the bad gene and delivering a healthy gene. If successful, this work positions them well to obtain FDA authorization to launch a clinical trial.
Developing Drugs that Mimic a Naturally Occurring Vision-Saving Protein — Several studies in animal models of retinal degeneration have shown that a naturally occurring protein called brain-derived neurotrophic factor (BDNF) effectively preserves photoreceptors and vision. However, for a number of reasons, BDNF is difficult to administer as a retinal therapy. Dr. Jeff Boatright of Emory University will be evaluating two drugs that mimic BDNF for the treatment of retinal degenerations. If Dr. Boatright’s lab studies of these drugs are successful, the treatments will be well-positioned for clinical trials.
Finding the Genetic Cause of a Juvenile Retinal Disease Known as North Carolina Macular Degeneration — Dr. Paul Wong of Emory University will be searching for the underlying genetic cause of an early-onset, autosomal dominant retinal disease known as North Carolina macular degeneration. While the condition affects many people in North Carolina, the disease has been reported in Caucasian and African-American families across the United States, as well as people living in other countries around the world including China, Australia, France and Italy. By understanding the genetic cause of this disease, researchers will be better positioned to develop treatments for it. Also, scientists believe that identifying the origin of North Carolina macular degeneration will also provide them with new insights into age-related macular degeneration.
Employing Next Generation Sequencing to Find New Disease-Causing Genes — Dr. Qin Liu of the University of Pennsylvania will be using an approach called whole-exome sequencing to identify new genetic variations that cause retinal degenerative diseases. Also known as next-generation sequencing, the approach targets exons, the genetic regions where disease-causing variations are most likely to occur. Exons provide information for the production of proteins. If a defect in an exon leads to a missing or incorrect protein, diseases can occur. The whole-exome approach has already been successful in identifying genes that cause both dominant and recessive forms of retinitis pigmentosa.
Advanced Retinal Imaging for Evaluating Treatment Effectiveness — Because retinal diseases often progress at varying rates over several decades, an effective treatment may not have a measurable impact on vision for several years. However, through advanced retinal imaging techniques such as adaptive optics, physicians and researchers can more quickly determine a treatment’s effect on the health of retinal cells long before vision improvement can be measured. Dr. Joseph Carroll at the Medical College of Wisconsin will be developing and enhancing retinal imaging techniques, such as adaptive optics, so that experts have better tools for assessing emerging treatments.
Gene Therapy for LCA and Autosomal Recessive Retinitis Pigmentosa — Approximately 10-15 percent of LCA cases and 3-4 percent of RP cases are caused by variations in the gene CRB1. While there is currently no treatment for these forms of disease, progress is being made on the gene therapy front for them. Dr. Jan Wijnholds of The Netherlands Institute for Neurosciences is developing an AAV gene therapy that can safely and effectively deliver a healthy gene to the inner cells in the retina that are affected by the CRB1 variations. The researchers are hopeful this work could lead to future clinical trials for these diseases.
- Bone Marrow Stem Cells in Clinical Trial for Retinal Diseases
- GenSight Receives $41.3 Million for Ocular Gene Therapy Development
- Stem Cell Pioneers Creating Retinal Patch to Restore Vision
- XLRS Natural History Study Beginning in Portland, Oregon
- Six Emerging Retinal Therapies Receive $3.1 Million in Foundation Funding