How Gene Therapy Can Reverse a Form of Congenital Blindness
In December of 2018, the Sanford Health International Board honored our work for an inherited retinal disease caused by mutations on the RPE65 gene, which leads to blindness, by naming us the winners of their inaugural Sanford Lorraine Cross Award. It was a gratifying and emotional moment, marking yet another milestone on what has been an incredible journey that has taken more than two decades—a journey to give better sight back to patients with an inherited type of vision loss. But more than 20 years later, we have been the drivers of a huge effort to bring patients and their families the first and only gene therapy approved by both U.S. and EU regulators for an inherited disease.
This inherited retinal disease affects thousands of people around the world—people who are born with poor vision and then slowly lose their sight over time. Often, they are only able to see the shape of an object, and only in bright sunlight. Our work uses gene therapy to deliver a normal copy of that disease-causing gene to help restore vision.
Spending your life in a laboratory can feel tedious and frustrating at times, even as you make incremental progress toward solving the challenges you face. As we looked around us at the award event, we were reminded that those years of hard work do pay off—not just for us, but for all scientists toiling right now and those who will follow, and most importantly for patients.
Brian Kaspar, whose work cures floppy baby syndrome, and James Wilson, who discovered many vectors being used in gene therapy studies, also were nominated. We couldn’t have asked for better company.
Thinking back, we were lucky to have been so naive when we began this work, because if we had known in advance about the dozens of challenges that were to come, including developing and validating a novel endpoint, coming up with a rigorous trial design for an ultrarare disease population, bringing manufacturing to commercial standards, and building a database of the natural history of this disease, we may never have started.
There’s the delicate nature of the procedure itself, injecting the vector into cells on the back of someone’s retina, and the fact that, when we started, there was no test to measure clinical impact. You can’t ask someone to read the standard eye chart if they can’t even see it. To overcome this barrier, we created a first-of-its-kind mobility test that helps measure changes in functional vision. After that we had to figure out how to get this new therapy approved for use in patients, as there was no clear path for pediatric gene therapy drug development at the time. We had no choice but to focus on solving the day's problems, so that we could ensure there was a tomorrow for the research program.
And we knew we could not do this alone; no scientist or researcher can. Spark Therapeutics was created in 2013 to bring vector manufacturing up to commercial standards and to develop solutions for the complex issues of reimbursement and access that are presented by a one-time, high-value therapy. While we had setbacks along the way, we did not let them deter us. We always looked for another way.
Spark Therapeutics submitted more than 65,000 pages of documentation to the U.S. Food and Drug Administration (FDA) and went through a full day of questioning by their advisory committee. We received a unanimous recommendation for approval by the committee, and the therapy was subsequently approved by the FDA. We received approval from the European Commission (EC) in 2018.
And of course, our journey to help patients and families living with RPE65 gene mutations is not over. We continue to look for ways to make genetic screening for inherited retinal diseases a standard practice. The stories we have heard have cemented our conviction that this must happen, including one experience we heard from a family that was told their child had autism. However, the truth was the child could not see. This is emblematic of the circuitous route some families take on their journey to a diagnosis. But when a disease is degenerative like this one, every moment matters.
Our successes are thrilling, but what really inspires us is that this breakthrough created a path for more potential gene therapy treatments for blindness and other devastating inherited diseases, creating the potential to impact the lives of even more patients and families. Data show that there are more than 2,500 gene therapy trials under way right now for a range of genetic diseases. Through gene therapy, medicine can achieve the full measure of the promise of the Human Genome Project: better treatments for people born with serious genetic disease.
This is an astonishing time to be a physician-scientist. The frontier of gene therapy is moving ever closer to wider applications for other diseases, and we are so grateful to be part of that.
Every time any of us in the scientific world sees a measure of success with gene therapies—or learns from a failure—we inch closer to better access for patients to treatments that improve and save lives, and to improving the process from discovery to approval. It’s what has kept us on this journey and promises incredible progress ahead in helping other patients and families living with genetic diseases.