Abstract:

Is there a need for small molecule neuroprotectants in inherited retinal degeneration (iRDs)? iRDs are a heterogeneous cluster of diseases which lead to blindness in 1 in every 2–3000 people. A plethora of causative genetic defects were revealed in the last 30 years. Current research focuses on development of pharmacolog-ical, biological or mechanical implant treatments. Gene therapy demonstrated success in patients with specific genetic mutations and Luxturna, recently approved by the FDA for RPE65 related disease, entered the market at a cost of $425,000 per eye. Given over 250 genes link to iRDs, gene-specific therapy for each gene is challenging and limits widespread applicability. Cell-based approaches aim to replace defective photoreceptor or retinal pigment epithelium (RPE) cells, however concerns remain over long-term benefit, safety and integration of transplanted pho-toreceptor cells. Human embryonic stem cell (hESC) derived RPE patches appear more promising when transplanted into an initial cohort of patients affected by age-related macular degeneration (AMD). An alternative to replacing defective cells or genes is to identify neuroprotective factors preventing vision loss. Drug treatment has several advantages including: i) bypass permanent modifications and associated risks ii) ability to fine-tune an effective and safe dose for each patient, iii) can easily stop treatment if adverse effects en-countered and iv) is relatively less expensive compared to gene- or cell-therapy.