Coimbra researchers report improvement in degenerative eye condition following innovative gene therapy

A multidisciplinary team from the University of Coimbra (UC) and the Coimbra Local Health Unit (ULS Coimbra) has provided new insights into the impact of gene therapy on the brain of patients with a type of hereditary retinal dystrophy associated with severe bilateral vision loss.

This study specifically examined the brain’s response to visual stimuli in individuals who received an innovative gene therapy treatment for hereditary retinal degeneration linked to the RPE65 gene. (Gene therapy works by replacing faulty genes). This specific treatment, known as voretigene neparvovec, involves a surgical procedure called vitrectomy, during which a sub-retinal injection is administered to patients.

While the benefits of this therapy for patients’ visual function had already been well documented, the researchers went a step further by identifying changes in regions of the cerebral cortex associated with vision following treatment.

In the scientific article 'Improvements induced by retinal gene therapy with voretigene neparvovec depend on visual cortical hemispheric dominance mechanisms', published in the journal Communications Medicine by Nature Portfolio, the researchers detail the improvements observed in participants of the study.

The RPE65 gene plays a vital role in vision. Patients with retinal degeneration linked to this gene experience severe central vision impairment, night blindness, and peripheral vision loss. The team assessed all patients before and one year after the treatment and observed significant improvements in patients' light sensitivity, particularly in low-light environments, using retinal imaging, visual tests conducted under varying lighting conditions, and functional MRI scans.

Miguel Castelo-Branco, a professor at the Faculty of Medicine of the University of Coimbra (FMUC) and director of the Coimbra Institute for Biomedical Imaging and Translational Research (CIBIT) at the Institute of Nuclear Sciences Applied to Health (ICNAS), explains that, surprisingly, the improvement observed by his team “is due not only to the retinal cells treated with gene therapy, but also to the brain’s ability to respond to the procedure.” He adds that “the regions of the right hemisphere of the brain responsible for processing visual information were those that showed the strongest response to the treatment.” Dr Castelo-Branco is also the senior author of the study.

The inclusion of the ULS Coimbra research team in the ERN-EYE consortium, a European network of experts on rare eye diseases spanning 24 EU countries, was also pivotal to this study. The network’s goal is to enhance understanding and monitoring of over 900 rare eye conditions, which are the leading cause of visual impairment and blindness among children and young adults across Europe.

The neuroscientist also stresses that, in addition to demonstrating the positive effects of gene therapy in treating this RPE65-associated disease, the results also suggest that rehabilitation, including visual training, could further improve patients’ responses to gene therapy. There is growing evidence of the need to ‘retrain’ brain circuits, even in cases where therapy targets the sensory organs. "This approach is applied in hearing, for example, where cochlear implants are followed by auditory rehabilitation involving speech therapists."

The scientific article is available here.