Treating people who are blind with gene therapy can not only restore their vision, it can also strengthen visual pathways in the brain, even in people who have been nearly blind for decades, researchers say.
Since 2007, clinical trials using gene therapy have often dramatically restored people's sight. Dozens of children and adults who were blind or near blind have become partially sighted, gaining the ability to navigate almost normally visually.
"Seeing how their visual function has improved and how it affects their daily lives has been extraordinarily gratifying," study co-author Dr. Jean Bennett, a gene therapist at the University of Pennsylvania in Philadelphia, told Live Science.
The basic strategy for these clinical trials is to inject a harmless virus that inserts good copies of genes that are defective in the individual. These genes are inserted into cells in the retina, the tissue that lines the inner eyeball and senses light.
"The results are amazing — a miracle," study lead author Manzar Ashtari, a neuroscientist at the University of Pennsylvania in Philadelphia, told Live Science. [5 Crazy Technologies That Are Revolutionizing Biotech]
But a question dogging these clinical trials is how well the brain's visual pathways can recover even if a person's retinal function has improved. The visual pathways are bundles of nerve fibers that connect the retina in the eye to the visual cortex in the brain, where visual information is processed. After years of near-total blindness, unused pathways inevitably weaken and shrink.
The new findings show that restoring a person's sight with gene therapy also helps strengthen the visual pathways of the brain.
The researchers looked at 10 patients with a rare inherited disease called Leber's congenital amaurosis Type 2 (LCA2), which causes the retinas to degenerate slowly. People with this disease typically have limited vision at birth and then progressively lose their remaining vision, becoming complete blind by midlife. The patients in the study each underwent gene therapy in only one eye, the one with the worst vision, as part of a study to test if the operation was safe.
About two to three years after the gene therapy treatments began, the researchers used an advanced magnetic resonance imaging (MRI) technique to scan deep into the participants' brains. The investigators found that not only were the visual pathways of the patients' treated eyes nearly as robust as those of people of the same age who had normal vision, but also that the patients' untreated eyes had weaker visual pathways.
This suggested that regaining sight helped rebuild visual pathways on the treated side, the researchers said. This capacity for the brain to renew itself is called brain plasticity.
"We see with our eyes — and our brain, Ashtari said. "If brain plasticity did not exist, even though gene therapy happened in the retina, the patients would not be able to see," he said.
Contrary to old ideas that the brain does not change much, a growing amount of research shows that the brain constantly changes.
Moreover, in this study, the changes happened even though many of the patients were adults in their 20s, and one was even 45. Scientists had thought the ability of the nervous system to rebound was greatly reduced in people of this age.
"Brain plasticity is not just for kids — it is for all ages," Ashtari said. "Certainly, plasticity is much more rapid in kids, but we can see improvements in older patients as well."
The data also hinted that the patients' visual pathways were typically in better shape after more time had elapsed since the person had undergone gene therapy. This suggested that the visual pathways continued to improve with use, while the visual pathways associated with untreated eyes showed a clear decline with time.
"The more signals get sent through the pathways, the stronger they get," Ashtari said.
The patients in this study have since gone on to receive the gene therapy in the eyes that were initially left untreated. Bennett and her colleagues are now working on a larger, phase 3 clinical trial to determine whether their gene therapy can be used more widely as a treatment. The FDA is expected to review results from this trial next year. "This could lead to the first approved gene therapy drug in the United States," Bennett said.
Because the visual pathways of the patients' treated eyes get better the more they get used, Ashtari suggested exploring whether eye exercises might help the visual pathways improve more quickly. "Just like rehabilitation can help speed up the process of healing with injuries to the shoulder, back or knee, I believe eye exercises for the eyes and brain right after gene therapy will help patients heal much faster."
The scientists detailed their findings online in the July 16 issue of the journal Science Translational Medicine.