Wolfgang Miesbach: From Failed Intravitreal Trials to Real Benefit – Subretinal AAV8 Gene Therapy in Pediatric X-Linked Retinoschisis
Wolfgang Miesbach, Professor of Medicine at Frankfurt University Hospital, shared a post on LinkedIn about a recent article by Licong Liang, he and his colleagues co-authored, published in NEJM, adding:
“From failed intravitreal trials to real benefit:subretinal AAV8 gene therapy in pediatric X‑linked retinoschisis.
Yesterday’s NEJM study reports 1‑year data on subretinal AAV8‑based gene therapy (scAAV8‑hRS1) for X‑linked retinoschisis (XLRS) in children and adolescents, after earlier intravitreal AAV trials largely failed to show efficacy beyond isolated, transient schisis closure.
Patients
12 boys, 5–18 years, genetically confirmed RS1 variants
Single subretinal injection of scAAV8‑hRS1 (7.5×10¹⁰ or 1×10¹¹ vg) into the worse eye
Excluded: recent carbonic anhydrase inhibitors,AAV8‑neutralizing antibodies ≥1:1000
Vector and delivery
Self‑complementary AAV8 vector with codon‑optimized human RS1 cDNA (scAAV8‑hRS1)
Rhodopsin kinase promoter to photoreceptor‑selective expression
Subretinal route chosen to improve photoreceptor transduction versus intravitreal delivery, which in prior XLRS trials did not produce consistent functional or structural benefit
- Safety at 52 weeks
- 56 adverse events
- No grade ≥3 events
- No ocular inflammation reported
- One macular hole in the treated eye at week 1 in a structurally fragile macula
Efficacy: clear signals.
Subretinal scAAV8‑hRS1 led to complete closure of schisis cavities in all treated eyes, substantial reduction in central retinal thickness, and a meaningful BCVA gain in the treated eye compared with the fellow eye at 1 year.
First pediatric XLRS gene therapy study to show consistent closure of schisis cavities in all treated eyes together with a meaningful BCVA gain versus the fellow eye.”
Title: Subretinal Gene Therapy for X-Linked Retinoschisis
Authors: Licong Liang, Kaiqin She, Chengda Ren, Rui Li, Meng Liao, Zhiyan Tao, Fanfei Liu, Jing Su, Ming Hu, Yiliu Yang, Xiaoyue Wang, Charlotte L. Zhang, Li Bao, Qin Chen, Kang Zhang, Yuquan Wei, Yang Yang, Fang Lu.
Other posts featuring Wolfgang Miesbach on Hemostasis Today.
-
Sep 13, 2026, 12:31Vishakha K. Kumar: ISTH Opens Public Comment Period on New Guidance
-
Sep 13, 2026, 12:13Tahsin Ara Mim: Takayasu’s Arteritis Case Report Secures 2nd Runner-Up
-
Sep 13, 2026, 11:26Tareq Abadl: When Good Samples Give Bad Numbers – Spotting EDTA Contamination in the Lab
-
Sep 13, 2026, 11:22Amanda Unsworth: Gratitude and Next Steps as Leadership Transitions at The Platelet Society
-
Sep 13, 2026, 11:18Mary Cushman: Covering Associations of Antiphospholipid Antibodies with Stroke
-
Sep 13, 2026, 11:13Mavis Agnes Kisakye: How Community Partnerships Are Driving Opportunity for Youths with Bleeding Disorders
-
Sep 13, 2026, 11:07Dianne E. van der Wal: Transforming Science into Art – The Launch of The Life, Function and Death of Platelets
-
Sep 13, 2026, 10:18Daniel Victor Ortigoza: Understanding Stroke, Risk Factors and Prevention
-
Sep 13, 2026, 08:13Selina Olwanda Ogweno: Expanding Access to Sickle Cell Care for Children and Young People