A hereditary retinal dystrophy that affects two siblings, who, however, manage to recover their sight thanks to gene therapy. Now they can better distinguish details and are able to move confidently in dimly lit environments, without fear of tripping over objects: the little brother and sister of 8 and 3 years, with the same form of hereditary retinal dystrophy, have regained important visual abilities later on. to treatment with gene therapy. The interventions were carried out in collaboration by the Ophthalmology units of the Agostino Gemelli IRCCS University Polyclinic Foundation and the Bambino Gesù Pediatric Hospital, as part of a project launched in 2021 for the joint management of pediatric and adult patients suffering from hereditary retinal degeneration. The little girl who regained her sight is the youngest patient in Italy to have received this treatment.
In 2021, the Italian Medicines Agency (Aifa) authorized the voretigene neparvovec gene therapy (trade name Luxturna) developed by Novartis for the treatment of rare forms of hereditary dystrophy of the retina in adult and pediatric patients. These are those forms caused by mutation of both copies (biallelic) of the RPE65 gene, responsible for the production of a key protein in the process of converting light into an electrical signal in the retina.
Leber’s amorous
The best known of the hereditary retinal dystrophies is retinitis pigmentosa (RP) from which the two treated siblings were affected in the earliest form – Leber’s congenital amaurosis. Retinitis pigmentosa can be caused by the mutation of about 100 genes involved in the mechanisms of vision.
One of these genes is RPE65, whose mutations on the two copies of the gene are very rare and affect about 1 in 200,000 people worldwide. On the basis of prevalence studies it is estimated that in Italy the subjects involved are between 100 and 120. Patients have problems with poor night vision, narrowing of the visual field and can manifest a severe and progressive reduction of vision up to blindness. It is, therefore, a progressive disease, responsible for serious disability, both in terms of education and integration into the world of work.
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A single injection of the healthy gene
The therapy consists of a single injection – “one shot” – into the subretinal space of both eyes of a functioning copy of the RPE65 gene. The healthy gene is carried inside the cells by an associated adenovirus, with modified genetic heritage, which acts as a vector. Once in the cells, the functioning copy of the gene is able to restore the patient’s vision in a meaningful and lasting way.
Access to treatment
In order to access the treatment, specific clinical inclusion parameters have been established. The correct clinical characterization of retinal dystrophy and the identification of the RPE65 gene mutation through a genetic test are of fundamental importance, in order to arrive at a correct diagnosis, evaluate the progress of the disease and set the correct therapeutic strategy.
The collaboration project of the two hospitals
In May last year, a framework agreement was signed between the Ophthalmology unit of the Agostino Gemelli IRCCS University Polyclinic Foundation, directed by Professor Stanislao Rizzoand that of the Bambino Gesù Pediatric Hospital, directed by professor Luca Buzzonetti, for the management of pediatric and adult patients with hereditary retinal degenerations. The goal is to improve the quality of healthcare provided to these patients by pooling resources and organizational skills. Through a diagnostic process carried out with common protocols, patients are included in specific registers for possible therapeutic strategies. The approval of the first gene therapy for a specific mutation due to hereditary retinal dystrophies such as Leber’s congenital amaurosis and early onset retinitis pigmentosa together with the selection of the Ophthalmology unit of Policlinico Gemelli as one of the Italian reference centers for related surgical procedure, led to the treatment of the first two pediatric patients affected by this pathology from the Infant Jesus.
Children looked after
The two children are 8 and 3 years old and live in Sardinia with their parents who arrived a few years ago in Italy from Senegal for work. The first to receive gene therapy was the boy who has been treated at the Child Jesus Ophthalmology unit since he was 3 years old. The diagnosis of retinal dystrophy, confirmed by genetic tests, allowed him to be entered in the register of patients eligible for voretigene neparvovec gene therapy immediately after approval by Aifa when he was already 7 years old. The therapy was administered to the right eye in October 2021 and to the left in December of the same year.
All visual parameters improved
The post-intervention follow-up course, completed in February 2022, showed a significant improvement in all subjective visual parameters, i.e. visual acuity (ability to discriminate spatial detail), visual field (ability to see peripherally) and twilight vision. The same is true for objective parameters through specific tests such as the FST (test that evaluates the sensitivity of cones and rods, the retinal cell population that allows us to see).
The youngest patient in Italy
The little sister, suffering from the same disease, is the youngest patient in Italy treated with gene therapy having just turned three years old. The first treatment took place in February 2022 and the second in June. For her too, the follow-up completed in recent days has shown a significant recovery of sight. A third patient of the Infant Jesus, aged 7, is currently a candidate for treatment.
The prospects
“Gene therapy for inherited retinal degeneration – he says Giancarlo Iarossi, referent of the path on retinal dystrophies within the Ophthalmology unit of the Bambino Gesù Pediatric Hospital – represents the first concrete cure to prevent or correct the complete decay of visual function and plays a fundamental role for future therapeutic strategies. Other forms of retinal dystrophies caused by various gene mutations are currently the subject of advanced clinical trials. The hope of the operators involved is to continue this project aimed at applying the most appropriate therapy according to the current knowledge on retinal degenerations to our common patients and to extend it in the immediate future to other mutations “.
The first therapy against these diseases
“Operating patients at a very young age and giving them back their sight is something that goes beyond our professional life and fully identifies with the mission of the Gemini and the Infant Jesus, to treat people with very serious disabilities using the results of the most advanced clinical research – says Professor Stanislao Rizzo, full professor of Ophthalmology at the Catholic University and director of the Ophthalmology Unit of the A. Gemelli University Hospital IRCCS. a short time ago. Finally today, even if only in a few patients, we are able to offer an effective treatment, the result of international scientific studies carried out in very few research and treatment centers in the world “.