PRPH2

Advancing Research Solutions for PRPH2-Associated Retinal Diseases COLUMBIA, Md., May 22, 2024 /PRNewswire/ -- The Foundation Fighting Blindness, the driving force in the global development of treatments and cures for blinding diseases, has announced the recipients of the first awards in the PRPH2 and Associated Retinal Diseases (PARD) Program. These grants mark a significant milestone in advancing research into retinal diseases caused by mutations in the PRPH2 gene. Continue Reading Andrew Goldberg, PhD, of Oakland University, and Yoshikazu Imanishi, PhD, of Indiana University Following an extensive international call for proposals, the Foundation has awarded nearly $1 million to two distinguished researchers: Andrew Goldberg, PhD, of Oakland University, and Yoshikazu Imanishi, PhD, of Indiana University. These awards are the first of six anticipated grants to be distributed over three years through the collaboration between the Foundation Fighting Blindness and the Nixon Visions Foundation. "These inaugural grants represent a significant investment in cutting-edge research aimed at understanding and ultimately treating PRPH2-related retinal diseases," says Amy Laster, PhD, senior vice president, science strategy and awards at the Foundation Fighting Blindness. "By funding these projects, we are accelerating progress toward innovative therapies that could restore vision and improve the quality of life for individuals affected by these conditions. This is a pivotal moment in inherited retinal disease research, and we are excited to see the transformative discoveries that will emerge from this collaboration." "We are proud to provide financial support to these exceptional researchers in their pursuit of novel therapies for PRPH2-associated retinal diseases," added Brandon Nixon, chief executive officer at the Nixon Visions Foundation. "We look forward to the important discoveries these initial grants will yield as part of our foundation's multi-year PRPH2 research funding initiative. We are committed to advancing the science that will lead to treatments and cures for these diseases." Mutations in the PRPH2 gene are a leading cause of retinal degenerations such as retinitis pigmentosa and certain macular dystrophies. The focus of the research funded by these awards include: Dr. Andrew Goldberg of Oakland University – Natural History and AAV-Mediated Interventions for Dominant Negative and Haploinsufficient Mouse Models of PRPH2-Associated Disease. These studies will provide thorough characterization of two mouse models of PRPH2-associated disease and test whether providing a functional copy of PRPH2 can prevent or slow disease progression. Dr. Yoshikazu Imanishi of Indiana University – Elucidating Pathophysiological Mechanisms and Advancing High-Throughput Drug Discovery in PRPH2-Related Retinal Dystrophies. This study aims to identify small molecules that can help mutant PRPH2 localize to photoreceptor outer segments and to understand how rods and cones are differentially affected by mutant PRPH2 protein. The Foundation Fighting Blindness remains committed to driving progress in retinal disease research through strategic partnerships and targeted funding initiatives. With ongoing support from visionary collaborators like the Nixon Visions Foundation, the Foundation continues to champion innovative solutions that hold promise for those impacted by blinding diseases. The PRPH2 and Associated Retinal Diseases Program, established in partnership with the Nixon Visions Foundation, was unveiled in March 2023 during a joint workshop focused on PRPH2. This initiative emerged from a consensus among retinal disease experts regarding critical research gaps within the field: The need for a better understanding of PRPH2 basic biology, including its differential role in rods and cones. The development of high-throughput assays to determine the functional consequences of PRPH2 variants. The creation and characterization of accurate animal models. An improved understanding of disease heterogeneity. Studies that demonstrate proof-of-concept for therapeutic approaches, especially mutation-agnostic approaches. About the Foundation Fighting Blindness Established in 1971, the Foundation Fighting Blindness is the world's leading private funding source for retinal degenerative disease research. The Foundation has raised more than $915 million toward its mission of accelerating research for preventing, treating, and curing blindness caused by the entire spectrum of blinding retinal diseases including: retinitis pigmentosa, macular degeneration, and Usher syndrome. Visit FightingBlindness.org for more information. About the Nixon Visions Foundation Nixon Visions Foundation is dedicated to the support of organizations and individuals who are striving to reach their potential. Based in San Diego, the foundation provides scholarships and other funding for education, science, and community programs. Its current initiative is to provide meaningful support for scientific research leading to critical treatments and, ultimately, cures for rare inherited retinal degenerative diseases through partnerships with the Foundation Fighting Blindness and UC San Diego Health's Shiley Eye Institute, each targeting rare gene mutations such as those of the PRPH2 gene. Visit . Media Contact: Chris Adams Vice President, Marketing & Communications [email protected] 410-423-0585 SOURCE Foundation Fighting Blindness

Session to have special translational research emphasis on PRPH2 and inherited macular dystrophies. COLUMBIA, Md., Jan. 25, 2023 /PRNewswire/ -- The Foundation Fighting Blindness, the world's leading organization committed to finding treatments and cures for blinding retinal diseases, in partnership with the Nixon Visions Foundation and the Shiley Eye Institute, at the University of California, San Diego, will host the free in-person PRPH2 and Associated Retinal Diseases Workshop on March 29–31, 2023, at the Hilton La Jolla Torrey Pines in San Diego, CA. Registration information can be found at . The PRPH2 and Associated Retinal Diseases Workshop is designed to bring together leading experts from academia and industry, to discuss openly, and in detail, what is known about PRPH2 disease pathology, disease models, clinical characteristics, and therapeutic approaches. In addition, affected individuals and their families will attend to share their experiences with PRPH2 disease and to hear the latest developments for care, treatment, and strategies for therapies. The workshop will also serve as a launching point for the Nixon Visions Foundation sponsored funding initiative that will provide multiple annual grants to scientific teams addressing high-impact gaps in the field. Claire M. Gelfman, PhD, chief scientific officer, Foundation Fighting Blindness, along with Radha Ayyagari, PhD, Shiley Eye Institute, University of California, San Diego (UCSD), and Shyamanga Borooah, MD, PhD, Shiley Eye Institute, University of California, San Diego (UCSD), will serve as workshop co-chairs. In addition, representatives from academia and industry who will address the research landscape and emerging therapies include: Steve Daiger, PhD – Director, Laboratory for Molecular Diagnosis of Inherited Eye Diseases, Professor, Human Genetics Center, School of Public Health and Ruiz Department of Ophthalmology and Visual Science, UTHealth Muna Naash, PhD – John S Dunn Endowed Professor of Biomedical Engineering, University of Houston Vadim Arshavsky, PhD – Helena Rubinstein Foundation Distinguished Professor of Ophthalmology, Duke University Francois Paquet-Durand, PhD – Professor, Institute for Ophthalmic Research, Tubingen University Peter Quinn, PhD – Principal Investigator and Associate Research Scientist, Columbia University Fred K. Chen, MBBS, PhD – Associate Professor, Lions Eye Institute, Australia Rachel Heath Jeffery, MChD, MPH – Resident, Lions Eye Institute, Australia Deepak Lamba, MBBS, PhD – Associate Professor of Ophthalmology, University of California, San Francisco Shannon Conley, PhD – Assistant Professor of Cell Biology, The University of Oklahoma Health Sciences University Kari Branham, MS, CGC – Assistant Professor, Ophthalmology and Visual Sciences, Genetic Counselor, Inherited Retinal Dystrophy Clinic, Kellogg Eye Center, University of Michigan Rob Collin, PhD – Principal Investigator, Department of Human Genetics, Radboud University Medical Center David Birch, PhD – Scientific Director, Retina Foundation of the Southwest Daniel Chung, DO, MA – Chief Medical Officer, Sparing Vision Eric Daniels MD, MBA – Chief Development Officer, Kiora Pharmaceuticals Ash Jayagopal, PhD – Chief Science Officer, Opus Genetics "We are privileged to be partnering with the Nixon Visions Foundation and the Shiley Eye Institute, University of California, San Diego, to bring awareness, build a community across PRPH2-related retinal disease and accelerate related research on biological and therapeutic approaches," said Claire M. Gelfman, chief scientific officer of the Foundation Fighting Blindness. "Our hope is that through this workshop we will facilitate knowledge sharing to illuminate the current landscape and to identify key roadblocks impeding translation to therapies." To register for the PRPH2 and Associated Retinal Diseases Workshop and get the latest updates on the event, visit . About the Foundation Fighting Blindness Established in 1971, the Foundation Fighting Blindness is the world's leading private funding source for retinal degenerative disease research. The Foundation has raised more than $891 million toward its mission of accelerating research for preventing, treating, and curing blindness caused by the spectrum of blinding retinal diseases including: retinitis pigmentosa, macular degeneration, and Usher syndrome. Visit FightingBlindness.org for more information. About the Nixon Visions Foundation Nixon Visions Foundation is dedicated to the support of organizations and individuals who are striving to reach their potential. Based in San Diego, the foundation provides scholarships and other funding for education, training, social welfare, public information, and research. Its newest initiative is to provide meaningful support for scientific research leading to critical treatments and, ultimately, cures for rare inherited retinal degenerative diseases through partnerships with the Foundation Fighting Blindness and UC San Diego Health's Shiley Eye Institute, each targeting rare gene mutations such as those of the PRPH2 gene. Visit . About the Shiley Eye Institute The Shiley Eye Institute is the only academic institution in the San Diego area with comprehensive programs for the clinical care of patients with eye disorders, cutting edge research on surgical techniques and treatments of eye diseases, education in the field of ophthalmology and innovative outreach to the community. To learn more about the Shiley Eye Institute, visit . Media Contact: Chris Adams Vice President, Marketing & Communications [email protected] 410-423-0585 SOURCE Foundation Fighting Blindness

Researchers say they have successfully used a cell's natural process for making proteins to 'slide' genetic instructions into a cell and produce critical proteins missing from those cells. Johns Hopkins Medicine researchers say they have successfully used a cell's natural process for making proteins to "slide" genetic instructions into a cell and produce critical proteins missing from those cells. If further studies verify their proof-of-concept results, the scientists may have a new method for targeting specific cell types for a variety of disorders that could be treated with gene therapies. Such disorders include neurodegenerative diseases that affect the brain, including Alzheimer's disease, forms of blindness and some cancers. For those looking to develop treatments for diseases where cells lack a specific protein, it's critical to precisely target the cell causing the disease in each structure, such as the brain, to safely kickstart the protein-making process of certain genes, says Seth Blackshaw, Ph.D., professor of neuroscience in the Sol Snyder Department of Neuroscience and member of the Institute for Cell Engineering at the Johns Hopkins University School of Medicine. Therapies that don't precisely target diseased cells can have unintended effects in other healthy cells, he adds. Two methods currently used to deliver protein-making packages into cells vary widely in their effectiveness in both animal models and people. "We wanted to develop a gene expression delivery tool that's broadly useful in both preclinical and clinical models," says Blackshaw. One current method of sending biochemical packages involves so-called "mini promoters" that direct the expression, or protein-making process of certain stretches of DNA. Blackshaw says this method often fails to express genes in the right cell type. Another method, called serotype-mediated gene expression, involves delivering tools that latch on to proteins that stud the surface of certain types of cells. However, Blackshaw says such methods are hit-or-miss in their ability to specifically target only one type of cell, and they often fail to work in people even after successful testing in animal models. The current proof-of-principle study, described Oct. 1 in Nature Communications, has roots in previous research by Johns Hopkins Assistant Professor of Pathology Jonathan Ling, Ph.D., who published "maps" depicting how various cell types use alternative splicing of messenger RNA, a cousin of DNA, to construct genetic templates that produce an ever-changing set of proteins in the cell. The changes depend on a cell's type and location. Cells normally use alternative splicing to vary the types of proteins a cell can make. Ling's maps chart the patterns by which cells cut out introns, or extraneous sections of messenger RNA, and leave only the informative parts of genetic material, or exons, that actually express, or make, proteins. However, introns are normally very large -- sometimes millions of base pairs long and too big to package in currently available gene expression delivery systems. Ling found some 20% of alternative splicing patterns contained sections of intron DNA small enough to package into the gene expression delivery systems Blackshaw wanted to test. Fortunately, for their purposes, the alternative splicing patterns were similar in both mouse and human DNA, and so potentially, applicable to both preclinical research and clinical use. Together with then-postdoctoral fellow Alexei Bygrave, now an assistant professor at Tufts University, Blackshaw and Ling made packages of alternative spliced messenger RNA that could be delivered into cells via a benign virus. They dubbed the packages SLED, for splicing-linked expression design. When the package slides into a cell, it opens there. Because the SLED system is not naturally integrated into the genome, the research team added genetic "promoters" that spark the production of proteins from the packaged SLED product. The Johns Hopkins Medicine researchers constructed SLED systems for laboratory-cultured excitatory neurons and photoreceptors and were able to produce proteins exclusively in those cell types about half the time. Current minipromoter systems typically get the proteins in the right place about 5% of the time. The team also injected SLED packages into mice with photoreceptors in the retina that lack a functional PRPH2 gene, which causes retinitis pigmentosa, a disease affecting the retina. The team found evidence that the SLED packages helped produce PRPH2 proteins in the photoreceptors of the treated mice. In human ocular melanomas cultured in the laboratory, the scientists delivered SLED packages into only melanoma cells that lack the SF3B1 gene. The SLED package released RNA-producing protein that made the melanoma cells die. Blackshaw says the SLED system's best potential may be in combination with other gene delivery systems, and his lab is looking into methods to miniaturize introns to accommodate larger-size introns into SLED systems. Blackshaw and Ling have filed for patents that involve SLED technology. The research was funded by the National Institutes of Health (RF1MH123237, R24EY027283, K08EY027093, R01EY033103, 2T32EY007143), a Stein Innovation Award from Research to Prevent Blindness, the Wilmer Eye Institute, the National Science Foundation, a Johns Hopkins Kavli NDI Fellowship, and a Johns Hopkins IDIES Seed Fund. Other researchers who contributed to the work include Clayton Santiago, Rogger Carmen-Orozco, Vickie Trinh, Minzhong Yu, Yini Li, Ying Liu, Kyra Bowden, Leighton Duncan, Jeong Han, Kamil Taneja, Rochinelle Dongmo, Travis Babola, Patrick Parker, Lizhi Jiang, Patrick Leavey, Jennifer Smith, Rachel Vistein, Megan Gimmen, Benjamin Dubner, Eric Helmenstine, Patric Teodorescu, Theodoros Karantanos, Gabriel Ghiaur, Patrick Kanold, Dwight Bergles, Ben Langmead, Shuying Sun, Kristina Nielsen, Neal Peachey, Mandeep Singh, W. Brian Dalton, Fatemeh Rajaii and Richard Huganir.