Recent Scientific Advances
The Foundation Fighting Blindness drives the research that will provide preventions, treatments, and cures for people affected by retinal degenerative diseases. Foundation-funded scientists are innovative leaders in the development of highly promising genetic, pharmaceutical, cell-based, and nutritional therapies.
FFB/Industry Treatment Development Case Studies
FFB Paves the Way for Commercializing Gene Therapies
An emerging, vision-restoring gene therapy for a devastating retinal disease is poised for Food and Drug Administration (FDA) approval. If it gets the regulatory nod, it will be the first gene therapy to receive FDA approval for the eye or an inherited condition.
The story of this groundbreaking treatment began with discovery of the gene RPE65 nearly 25 years ago at the National Eye Institute, and continued when the Foundation Fighting Blindness (FFB), the world’s leading private funding source for inherited retinal disease (IRD) research, invested $10 million in studies that linked mutations in RPE65 to blindness, and advanced an RPE65 gene therapy into clinical trials.
AGTC Leverages Funding from Foundation Fighting Blindness to Garner Major Investments
In the early 1990s, scientists began discovering the genetic defects causing blinding, inherited retinal diseases and saw a unique opportunity to overcome them. They envisioned gene therapy — delivering healthy genes to the retina to replace the bad — as an elegant approach to saving and restoring vision. Furthermore, a single injection of gene therapy would likely halt or reverse the disease process and work effectively for several years, perhaps the patients’ lifetimes.
Research Investment from Foundation Fighting Blindness Supports Emerging Company to Bring Gene Therapy for Rare Blinding Disease Closer to Reality
Spark Therapeutics, a gene therapy company developing an investigational gene therapy for people living with RPE65-mediated inherited retinal diseases, is currently in the process of completing its biological licensing agreement (BLA) with the U.S. Food and Drug Administration (FDA). If approved, it would be the first gene therapy for any genetic disease to be approved in the United States. The treatment involves delivering a functional copy of a mutated gene directly to the retina. The hypothesis is that this functional copy of the gene produces the necessary protein to slow the progression of disease and restore function in the retinal cells.
Advancements in Therapy Development
ABCA4 Midigenes Reveal the Full Splice Spectrum of All Reported Noncanonical Splice Site Variants in Stargardt Disease
Based on the work of Riccardo Sangermano, Mubeen Khan, Stephanie Cornelis, PhD candidates in the group of Professor Frans Cremers in the Department of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands, a new approach was recently published in the renowned journal Genome Research which enables the systematic and quick testing of putative causal sequence variants for their effect on RNA splicing and, thereby, on the protein.
Landmark Gene Therapy Restores Vision in Children and Young Adults
More than 100 children and young adults who were virtually blind have had some vision restored, thanks to an innovative gene therapy to cure a severe form of retinitis pigmentosa known as Leber congenital amaurosis (LCA) caused by mutations in the RPE65 gene. The individuals have participated in clinical trials of the treatment at the Children’s Hospital of Philadelphia (CHOP), Moorfields Eye Hospital in London, the Universities of Pennsylvania and Florida, and other centers around the world. One nine-year-old boy has put away his white cane and can now see the blackboard at school. A young woman was able to see fireflies for the first time after receiving the treatment. The CHOP clinical trial, sponsored by Spark Therapeutics, completed its final phase in which participants between the ages of 4 and 44 were better able to complete a mobility course after treatment. Thanks to these encouraging results, Spark will be seeking FDA approval for the gene therapy. If approved, it would be the first-ever FDA-approved gene therapy for the eye or any inherited disease. The Foundation funded much of the preclinical research that made these LCA gene-therapy clinical trials possible.
Company Launches Stem Cell Clinical Trial
ReNeuron, a stem-cell therapy development company in the United Kingdom, has launched a Phase I/II clinical trial for its stem-cell-derived therapy. The trial is underway at the Massachusetts Eye and Ear Infirmary. The emerging therapy involves the transplantation of retinal progenitor cells — cells that haven’t completely developed into photoreceptors. The therapy may save or even restore vision in people with retinitis pigmentosa, Usher syndrome, and potentially other retinal diseases. The Foundation funded decades of critical lab research to make the ReNeuron therapy possible.
Researchers Advance Retinal Patch Derived from Stem Cells
The Foundation Fighting Blindness has been funding David Gamm, MD, PhD, University of Wisconsin, Madison, for a decade to develop stem-cell-derived treatments for retinal diseases. Dr. Gamm’s innovative retinal patch — consisting of photoreceptors and support cells known as retina pigment epithelium — holds promise for restoring vision in people with macular diseases including age-related macular degeneration and the leading inherited form of macular degeneration, known as Stargardt disease. A company known as Opsis was recently formed by Dr. Gamm and his collaborators to move the therapy into and through a clinical trial and out to the patients who can benefit from it.
Optogenetic Therapy in Clinical Trial for Advanced RP
RetroSense Therapeutics reported that three participants have received injections of its potential optogenetic therapy, known as RST-01, in a Phase I/II clinical trial. The patients were given the lowest dose of RST-01, and no adverse ocular events were observed. Furthermore, the treatment showed some biological activity. The treatment is designed to provide vision to people who are completely blind from conditions such as retinitis pigmentosa. The Foundation funded earlier lab research that helped make this clinical trial possible.
Vision-Restoring Bionic Retina Receives FDA Approval
The Argus II retinal prosthesis, a device that can restore some vision to people who are blind from advanced retinitis pigmentosa (RP) and other retinal conditions, has received market approval from the U.S. Food and Drug Administration and the European Medicines Agency. Developed by Second Sight Medical Products, the device is now being used by more than 100 people around the world. More than 20 years of research went into the development of the Argus II. The Foundation Fighting Blindness played a seminal role in its development, funding laboratory studies for an earlier version of the device.
Emerging Drug Holds Promise for Preserving Vision
The Foundation Fighting Blindness Clinical Research Institute (FFB-CRI) recently announced an investment of up to $7.5 million to advance a promising, emerging drug for retinitis pigmentosa (RP) into and through a Phase II clinical trial. Known as N-acetylcysteine-amide (NACA), the molecule is designed to slow vision loss by protecting retinal cells from oxidative stress. In previous FFB-funded lab studies at Johns Hopkins University, NACA slowed retinal degeneration in rodent models of RP. Nacuity, the company now working to advance the therapy, plans to launch a Phase II clinical trial in 2018.
Emerging Treatment for Retinal Diseases Gets the Message Right
In about 12 percent of all retinal degenerative diseases, the translation of genetic messages (mRNA) for the production of critical proteins stops prematurely, leading to the production of nonfunctional proteins and resulting in vision loss. In simple terms, it’s as if someone stops reading a sentence halfway through, and the resulting message doesn’t make sense. These translational errors are due to what is known as premature termination codons or PTCs. In a Foundation-funded study at the Johannes Gutenberg University in Mainz, Germany, Uwe Wolfrum, PhD, and his team are evaluating a drug that can “read through” PTCs in retinal cell cultures and mouse models of Usher syndrome type 1C. The drug enables the cell to read the complete message and make the right protein.
Gene Therapy Clinical Trial Underway for Stargardt Disease
The first-ever gene therapy clinical trial for Stargardt disease is underway at Oregon Health & Science University’s (OHSU) Casey Eye Institute in Portland and the Hôpital Nationale des Quinze-Vingts in Paris, France. The treatment is being developed by the pharmaceutical company Sanofi. The Foundation Fighting Blindness funded many of the pivotal lab studies making the StarGen gene therapy clinical trial possible.
Stargardt Disease Natural History Study Will Help Prepare for Future
The Foundation Fighting Blindness Clinical Research Institute has launched a natural history study of people affected by Stargardt disease. Known as ProgSTAR, the study has three primary goals: 1) Determine the best outcome measures to accelerate evaluation of emerging treatments, 2) better understand disease progression for selecting future clinical trial participants, and 3) identify potential participants for forthcoming clinical trials. The study has enrolled about 250 patients in 10 international clinical centers.
Vision Improvements Reported in Choroideremia Gene Therapy Clinical Trial
Initial results for the groundbreaking choroideremia gene therapy clinical trial conducted by Oxford University researchers in the United Kingdom are very encouraging. The emerging treatment has been safe thus far. In addition, five of six participants in the initial study group have sustained vision preservation or improvements in their treated eyes for more than three years. The two patients who entered the trial with the worst visual acuity showed significant improvements in reading an eye chart. The Foundation Fighting Blindness provided funding over two decades for lab studies that helped make the choroideremia gene therapy clinical trial possible.