Retinitis Pigmentosa (RP) is a group of inherited retinal degenerations that leads to the progressive loss of photoreceptors, initially causing night blindness and eventual tunnel vision. For decades, the therapeutic landscape offered limited options beyond supportive care and managing complications. However, the last few years have ushered in a transformative era driven by a deeper understanding of the hundreds of genetic mutations responsible for the disease, paving the way for targeted genetic interventions that address the disease at its source.

The advent of gene therapy has provided the first disease-modifying treatment for a subset of RP patients. Voretigene neparvovec (Luxturna) is the first FDA-approved gene therapy for patients with biallelic mutations in the RPE65 gene, which is a rare, but significant, milestone. This therapy works by delivering a healthy copy of the RPE65 gene directly into the retinal cells using an adeno-associated virus (AAV) vector, enabling the cells to produce the necessary protein to restore the visual cycle. This groundbreaking development has spurred massive investment and research across the entire therapeutic space dedicated to retinal dystrophies, confirming the immense promise of genetic medicine.

Beyond RPE65, numerous gene therapies are in advanced clinical trials targeting other common mutations, such as those in the RPGR gene (for X-linked RP) and the USH2A gene (for Usher syndrome). The ongoing challenge involves developing safe and efficient delivery methods for the gene payload, typically via subretinal or intravitreal injection, to ensure the therapeutic DNA reaches the correct population of viable cells without causing adverse immune reactions. The success of these trials will continue to expand the population of patients who can benefit from restorative treatments.

FAQ

• What is the goal of RPE65 gene therapy? It aims to replace the non-functioning RPE65 gene with a functional copy in the retinal cells to restore their ability to respond to light and improve functional vision.

• Is Luxturna a cure for all RP? No, it is currently approved only for patients with a confirmed diagnosis of biallelic RPE65 gene mutations and sufficient viable retinal cells.