Will gene therapy, stem cell therapy or low-vision devices have a greater impact on patient care for inherited retinal dystrophies in the next 5 years?
Each approach will likely have merit
“Inherited retinal dystrophies” is a heterogeneous group of disorders, and 5 years is a pretty short timeline. While the targeted elegance of replacing a defective gene with its normal counterpart has proven successful, the timing of treatment, the duration of effect, the mechanism of drug delivery and immunogenicity are important questions whose answers may be as heterogeneous as the diseases themselves. For RPE65 deficiency, clearly the answer is “gene therapy” as Spark Therapeutics will likely gain FDA approval for its AAV2-hRPE65 product. While there are a handful of other genes under study at this time, they are probably more than 5 years away from FDA approval. The study of CRISPR-Cas9 gene editing for dominant negative disease and the potential for optogenetic restoration of visual function (in a genome agnostic fashion), while attractive, are at early stages. There are hundreds of genes whose mutation is associated with inherited retinal disease, and given our current pace of acquiring preclinical data, executing human clinical trials and getting FDA approval, it will take time for significant impact. This process needs to be accelerated.
Stem cell therapy, while having the advantage of being genome agnostic, is poorly understood. There is little convincing data to suggest that retinal precursor cells, when introduced into the subretinal space, undergo transformation that recapitulates the elegant and complex synaptogenesis that defines the normal retina.
While the currently approved low-vision devices have benefitted relatively few patients, “next gen” devices are likely to be more effective and less cumbersome. Significant improvement will be required for significant impact.
J. Timothy Stout, MD, PhD, MBA, is Sid W. Richardson Professor, Margarett Root Brown Chair and director of the Cullen Eye Institute at Baylor College of Medicine. Disclosure: Stout reports no relevant financial disclosures.