Retinal scans in the mouse model show that eyes treated with gene therapy (A) are thicker than untreated eyes (B). Similarly, functional electrical studies in treated eyes show a greater response to light (C) compared with untreated eyes (D). This shows that the gene therapy has successfully rescued the animal model from disease.
Inherited retinal disease is a major cause of untreatable childhood blindness. We inherit two sets of genes, one from our mother and one from our father. There are now over 300 genes associated with retinal disease. Most early-onset retinal degenerations result from recessive disease. Recessive disease occurs when we lose both sets of our inherited genes due to gene defects known as mutations. This results in the loss of function of a gene.
One way of treating recessive disease is by replacing the missing gene with gene therapy. Gene replacement therapy provides the missing genes allowing cells to function again. This approach has recently been successfully used for the first FDA approved treatment for inherited retinal disease in an early-onset retinal degeneration, called Leber Congenital Amaurosis.
We recently described a new model of early-onset retinitis pigmentosa caused by mutations in the gene mouse frizzled receptor protein (MFRP). The model replicates many of the features of human disease including early-onset retinal degeneration and a loss of retinal electrical response.
We tested a gene therapy to treat this model. We found that treatment using gene therapy was able to provide long-term rescue of both retinal degeneration and retinal electrical function in the model.
Successful long-term rescue of vision in the animal model is an important translational step. Using a similar approach, we plan to pursue clinical trials to treat patients with the similar genetic diseases to attempt to rescue their remaining vision. This work was in collaboration with Dr. Radha Ayyagari, UCSD.