Abstract
Retinal gene therapy has yet to achieve sustained rescue after disease onset – perhaps because transduction efficiency is insufficient (“too little”) and/or the disease is too advanced (“too late”) in humans. To test the latter hypothesis, we used a mouse model for retinitis pigmentosa (RP) that allowed us to restore the mutant gene in all diseased rod photoreceptor cells, thereby generating optimally treated retinas. We then treated mice at an advanced disease stage and analyzed the rescue. We showed stable, sustained rescue of photoreceptor structure and function for at least 1 year, demonstrating gene therapy efficacy after onset of degeneration. The results suggest that RP patients are treatable, even when the therapy is administered at late disease stages.
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Acknowledgments
The Barbara & Donald Jonas Laboratory of Regenerative Medicine and Bernard & Shirlee Brown Glaucoma Laboratory are supported by the National Institutes of Health [5P30EY019007, R01EY018213, R01EY024698, 1R01EY026682, R21AG050437], National Cancer Institute Core (5P30CA013696), the Research to Prevent Blindness (RPB) Physician-Scientist Award, unrestricted funds from RPB, New York, NY, USA. S.H.T. is a member of the RD-CURE Consortium and is supported by the Tistou and Charlotte Kerstan Foundation, the Schneeweiss Stem Cell Fund, New York State (C029572), the Foundation Fighting Blindness New York Regional Research Center Grant (C-NY05-0705-0312), and the Gebroe Family Foundation. The authors declare no conflicts of interest.
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Koch, S.F., Tsang, S.H. (2018). Success of Gene Therapy in Late-Stage Treatment. In: Ash, J., Anderson, R., LaVail, M., Bowes Rickman, C., Hollyfield, J., Grimm, C. (eds) Retinal Degenerative Diseases. Advances in Experimental Medicine and Biology, vol 1074. Springer, Cham. https://doi.org/10.1007/978-3-319-75402-4_13
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DOI: https://doi.org/10.1007/978-3-319-75402-4_13
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