Medically reviewed by Susan Kerrigan, MD and Marianne Madsen
An experimental gene therapy restored the vision of a patient with a rare type of childhood blindness, according to a study published in Nature Medicine.
Researchers at the University of Pennsylvania Perelman School of Medicine injected patients suffering from a rare retinal disorder called Leber congenital amaurosis (LCA) with an antisense oligonucleotide called sepofarsen, an experimental RNA therapy. Sepofarsen stimulates production of a protein called CEP290 in the eye’s photoreceptors, potentially leading to enhanced sight.
10 patients received the drug repeatedly over three months and all experienced improvements in their vision, but one patient dropped out of the study after receiving his initial dose due to concerns over side effects. In the months after being injected with sepofarsen, however, the patient noticed that his vision was slowly coming back.
The effect reached its peak at two months after the initial shot, but improved vision persisted in the patient even 15 months after receiving his dose.
An unprecedented development
The study’s researchers didn’t expect the drug to have such a significant effect, but nonetheless, they see it as a good sign for the future of RNA-based gene therapies. They think their work could be used in treating other ciliopathies – diseases linked to genetic mutations resulting in the abnormal function of cilia, a type of sensory organelle on cells.
“This work represents a really exciting direction for RNA antisense therapy. It’s been 30 years since there were new drugs using RNA antisense oligonucleotides, even though everybody realized that there was great promise for these treatments,” said Samuel G. Jacobson, MD, PhD, a professor of Ophthalmology at Penn Medicine who co-led the study.
Future opportunities
The researchers think sepofarsen was effective in treating LCA because the molecules of the sepofarsen RNA were small enough to enter the cell nucleus and remain there long enough to do their work. Antisense oligonucleotides like sepofarsen are being studied in additional trials for the treatment of other genetic eye diseases. One notable research project using gene therapy is being backed by the UK charity Fight For Sight.
“There are now, at least in the eye field, a series of clinical trials using antisense oligonucleotides for different genetic defects spawned by the success of the work in CEP290-associated LCA from [the authors of the study],” said Joan O’Brien, MD, chair of Ophthalmology in the Perelman School of Medicine and director of the Scheie Eye Institute.
With new therapies like sepofarsen showing success and other gene therapies already in the pipeline, it’s likely that we’ll see a cure for blindness in the next few decades – something that was once thought to be impossible.