The Foundation Fighting Blindness Plays an Essential and Expansive Role in Driving Genetic Research for Inherited Retinal Diseases.

Ben Shaberman,Todd Durham

doi:10.3390/genes10070511

Abstract

The Foundation Fighting Blindness leads a collaborative effort among patients and families, scientists, and the commercial sector to drive the development of preventions, treatments, and cures for inherited retinal diseases (IRDs). When the nonprofit was established in 1971, it sought the knowledge and insights of leaders in the retinal research field to guide its research funding decisions. While the Foundation’s early investments focused on gaining a better understanding of the genetic causes of IRDs, its portfolio of projects would come to include some of the most innovative approaches to saving and restoring vision, including gene replacement/augmentation therapies, gene editing, RNA modulation, optogenetics, and gene-based neuroprotection. In recent years, the Foundation invested in resources such as its patient registry, natural history studies, and genetic testing program to bolster clinical development and trials for emerging genetic therapies. Though the number of clinical trials for such therapies has surged over the last decade, the Foundation remains steadfast in its commitment to funding the initiatives that hold the most potential for eradicating the entire spectrum of IRDs.

Highlights

The founders of the Foundation Fighting Blindness had no idea how challenging the development of treatments and cures for inherited retinal diseases (IRDs) would be
The Foundation invested approximately $10 million in RPE65 gene therapy lab studies to enable the launch of the clinical trial in 2007 at the Children’s Hospital of Philadelphia (CHOP), which brought to fruition the vision of Drs Bennett and Maguire
For autosomal dominant IRDs, such as retinitis pigmentosa (RP) caused by mutations in RHO, the delivery of a replacement gene will not be sufficient; a therapy will need to silence the mutated allele encoding the toxic protein or the allele acting in a dominant-negative fashion

Summary

Introduction

The founders of the Foundation Fighting Blindness had no idea how challenging the development of treatments and cures for inherited retinal diseases (IRDs) would be Little did they know, it would take nearly two decades for Foundation-funded researchers to find the first IRD gene and more than 35 years to advance a gene therapy into a human study. The Foundation’s funding strategy has evolved from only funding basic lab research to better understand IRDs to getting treatments across the translational chasm known as “the valley of death”—that is, to the point where biotechnology and pharmaceutical companies would invest in their clinical and commercial development. While the Foundation has traditionally emphasized research to identify treatment targets and develop therapies for these genetic retinal conditions, its project portfolio has recently expanded to include natural history studies—ProgStar, for people with Stargardt disease, and RUSH2A, for those with USH2A mutations—as well as the global patient registry at www.MyRetinaTracker.org. Data from both My Retina Tracker and the natural history studies can accelerate clinical development by helping researchers identify more powerful and sensitive clinical endpoints

Patient Perspectives on the Progress of Genetic Research

In the Beginning

The Trajectory for Gene Therapy Development

Beyond Gene Replacement

Cross-Cutting Gene Therapies

Natural History Studies

My Retina Tracker

Conclusion