Txnip Gene Therapy for Three Types of RP in Mice

Article: Gene therapy shows promise in treating rare eye disease in mice
Source: eLife, via ScienceDaily  and NEI
Published: April 13, 2021

Effect of Txnip on ATP:ADP levels in RP cones
in media with different carbon sources

Retinitis pigmentosa (RP) is a genetic eye condition that results in progressive dysfunction or loss of the photoreceptors in the retina, beginning with loss of rod photoreceptors and later also affecting cone photoreceptors. Currently, more than 100 gene loci for retinitis pigmentosa have been mapped or identified. However, targeted gene therapies have only been able to treat specific gene defects rather than wider sets or families of the disease. As the lead author states, “A gene therapy that would preserve photoreceptors in people with retinitis pigmentosa regardless of their specific genetic mutation would help many more patients.” To find a gene-agnostic therapy that could apply more broadly, the researchers screened 20 potential therapies in mouse models of RP, selecting for therapies that target sugar metabolism based on the theory that cone photoreceptor degeneration in RP was due to loss of glucose supply. Their experiments found that a gene called Txnip, especially an allele called C247S, was most effective in treating RP across three different mouse models. C247S in particular helped the cone photoreceptors switch to alternative sources of energy and improved mitochondrial health. Additionally, the rescue effect of Txnip depends on lactate dehydrogenase b (Ldhb), suggesting that this therapy improves cone photoreceptor health by enhancing lactate catabolism. Combining Txnip gene therapy with additional gene therapies that reduced oxidative stress and inflammation provided additional cellular protection. The researchers intend to further their studies in animal models beyond mice before starting clinical trials in humans.

My rating of this study: ⭐⭐

Xue Y, Wang SK, Rana P, et al. "AAV-Txnip prolongs cone survival and vision in mouse models of retinitis pigmentosa." eLife.  10:e66240. 13 April 2021. https://doi.org/10.7554/eLife.66240