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Paul A Sieving; Bench to Bedside (and back): How basic research instructs clinical practice and vice versa – Gene Therapy for X-Linked Retinoschisis. Invest. Ophthalmol. Vis. Sci. 2017;58(8):4769.
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Presentation Description :
Developing a gene therapy program for human X-linked juvenile retinoschisis (XLRS) is the culmination of 10 years effort. Discovering the underlying pathobiology of the disease required murine studies at the bench and human studies in the clinic. Our XLRS trial is the first in vivo human gene therapy program developed within the NIH intramural program and NIH Clinical Center and illuminates a translational and regulatory pathway for other NEI investigators. XLRS is a substantial cause of genetic macular degeneration in young males and has higher population frequency than hemophilia B. It is characterized by structural retinal failure of macular cystic schisis cavities and by functional deficits from synaptic failure that interrupts normal visual neurosignaling. There currently are no effective therapies for XLRS. The path to initiating human gene therapy was highly interactive between bench and bedside. It required generating a transgenic XLRS mouse model and conducting basic studies of the murine pathology, designing the therapeutic gene vector, conducting pre-clinical toxicity and efficacy studies, and developing a clinical trial protocol. Following IND approval in November, 2014, we injected the first human patient in February, 2015 and are well along in the program (ClinicalTrials.Gov #NCT02317887).
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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