000			02956nam a2200265 4500
001			ESSALUD
005			20260805114331.0
007			ta
008			t pe ||||| |||| 00| 0 spa d
040			_aBMG
041			_aeng
100			_aLiang, Licong _eAutor _953941
245			_aSubretinal gene therapy for X-Linked retinoschisis
300			_apáginas: 2222-2234
520			_aBackground: X-linked retinoschisis is a recessive disease characterized by progressive macular degeneration and vision loss due to pathogenic variation in RS1. Methods: We administered a single subretinal injection of an AAV8 vector containing human RS1 complementary DNA (scAAV8-hRS1) into one eye of patients 5 to 18 years of age who had X-linked retinoschisis. The primary end point was safety during the 52-week period after injection. Secondary end points included the change from baseline to week 52 in the best corrected visual acuity (BCVA), retinal structure (assessed with swept-source optical coherence tomography; SS-OCT), the function of photoreceptor and bipolar cells (assessed with full-field electroretinography), and macular sensitivity to light (assessed with microperimetry). Results: A total of 12 patients were enrolled. The dose-escalation phase included two cohorts of 3 patients each who received scAAV8-hRS1 at a dose of 7.5×1010 or 1×1011 vector genomes. In the dose-expansion phase, 3 additional patients were enrolled in each cohort. Overall, 56 adverse events were reported during the 52 weeks after surgery. No patient was reported to have an adverse event of grade 3 or higher or ocular inflammation. A macular hole in the treated eye was observed at week 1 in 1 patient. The mean increase at week 52 in the BCVA was 10.8 letters among the treated eyes and 2.4 letters among the untreated eyes. SS-OCT imaging showed closure of the macular schisis cavity by week 13 in the treated eye in all 12 patients. The mean change at week 52 in central retinal thickness was −437.7 μm among the treated eyes and −17.2 μm among the untreated eyes; the outer retinal layers in the treated eyes of 9 patients were continuous at week 52. No clinically meaningful changes in the function of photoreceptor and bipolar cells or macular retinal sensitivity were observed in the treated eyes. Conclusions: In this study of subretinal gene therapy with scAAV8-hRS1 in 12 patients with X-linked retinoschisis, there were no reports of adverse events of grade 3 or higher or ocular inflammation. Further clinical testing of scAAV8-hRS1 is warranted.
650			_aGENETICA _91105
650			_aOFTALMOLOGÍA _932364
650			_aPEDIATRÍA _96401
700			_aShe, Kaiqin _953942
700			_aRen, Chengda _953943
700			_aLi, Rui _953944
700			_aLiao, Meng _953945
773	0		_022717 _922641 _dMassachusetts NEJM Group _oNEJM008 _tThe New England Journal of Medicine _wESSALUD _x0028-4793
942			_cARTICULOS _e2026-08-03 _zSQB
999			_c22777 _d22777