Success of Gene Therapy in Late-Stage Treatment.

Retinal gene therapy has yet to achieve sustained rescue after disease onset - perhaps because transduction efficiency is insufficient ("too little") and/or the disease is too advanced ("too late") in humans. To test the latter hypothesis, we used a mouse model for retinitis pigmentosa (RP) that allowed us to restore the mutant gene in all diseased rod photoreceptor cells, thereby generating optimally treated retinas. We then treated mice at an advanced disease stage and analyzed the rescue. We showed stable, sustained rescue of photoreceptor structure and function for at least 1 year, demonstrating gene therapy efficacy after onset of degeneration. The results suggest that RP patients are treatable, even when the therapy is administered at late disease stages.