New gene therapy technique shows promise in stem cell model of retinitis pigmentosa

Although the 2017 FDA approval of Spark Therapeutics’ gene therapy Luxturna was considered a triumph for people with inherited eye disease, the product can only be used in patients with mutations in the RPE65 gene. Now, scientists in the United Kingdom say they’ve developed a gene therapy technique that could help a larger population of patients with retinitis pigmentosa.

Scientists at Trinity College Dublin and University College London zeroed in on the RP2 gene, which can become mutated to cause a number of forms of retinitis pigmentosa. Functional copies of the RP2 gene delivered to “mini retinas” were able to pump out a vital protein called rhodopsin, the researchers reported (PDF) in the journal Stem Cell Reports.

The mini retinas used in the study were three-dimensional organoids made from induced pluripotent stem cells and stem cells taken from patients with RP2-mutated retinitis pigmentosa. The organoids started losing the rod photoreceptor cells needed for proper vision at day 150. The gene therapy prevented that degeneration, the researchers said.

"In relative terms, it is now fairly easy to replace troublesome genes with functioning versions using non-harmful viruses, which is what we have done here,” co-author Ciara Shortall, Ph.D. a researcher in Trinity's School of Genetics and Microbiology, said in a statement. While there’s more work to be done, she added, “it is hugely exciting to have begun a journey that could one day provide an effective treatment to rescue eyesight."

Luxturna—now owned by Roche thanks to its $4.3 billion buyout of Spark—is the first of what could be a wave of gene therapies to treat eye disorders. More than 200 genes have been tied to retinitis pigmentosa, and mutations have also been linked to macular degeneration and other inheritable eye diseases, according to the University of Illinois College of Medicine.

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Not all efforts to develop gene therapies for eye diseases have succeeded. In December 2018, Biogen ended a $1 billion research deal with Applied Genetic Technologies after its gene therapy to treat X-linked retinoschisis failed a phase 1/2 trial. 

Meanwhile, academic groups continue to perfect models for studying eye diseases. In 2018, a team at Newcastle University in the U.K. announced they used stem cells from patients with RP to create a model retina. They went on to correct genetic defects with the gene-editing technology CRISPR-Cas9.

The Trinity College-UCL team hopes to use its mini retinas to study other common causes of blindness and to develop additional therapies to prevent them. The gene therapy the researchers developed to address mutations in RP2 will require further studies to determine the proper dose before it's ready for animal and human studies, the researchers said.