XLRS gene therapy — the first Chinese ophthalmic gene therapy to be published in the New England Journal of Medicine — demonstrates safety, durable visual improvement, and a favorable safety profile in patients with X-linked retinoschisis.
• Published in NEJM — first Chinese ophthalmic gene therapy to achieve this
• X-linked retinoschisis (XLRS) — a leading cause of juvenile macular degeneration
• AAV-mediated gene therapy — delivers functional RS1 gene to the retina
• Safety and efficacy — durable visual improvement with favorable safety profile
Introduction
X-linked retinoschisis (XLRS) is a monogenic inherited retinal disease caused by mutations in the RS1 gene, which encodes retinoschisin — a protein essential for maintaining the structural integrity of the retina. XLRS is one of the most common causes of juvenile macular degeneration in males, with an estimated prevalence of 1 in 5,000–15,000. Patients typically present with splitting of the retinal layers (schisis), leading to progressive visual loss, nystagmus, and strabismus.
Despite being first described over a century ago, no approved disease-modifying therapy exists for XLRS. Current management is limited to low-vision aids and treatment of complications such as retinal detachment.
In 2026, a Chinese research team from West China Hospital of Sichuan University published the first clinical data on XLRS gene therapy in the New England Journal of Medicine (NEJM) — marking the first Chinese ophthalmic gene therapy to be published in NEJM.
The Gene Therapy
The therapy uses a recombinant adeno-associated virus (AAV) serotype 8 vector encoding the human RS1 gene. Delivered via subretinal injection, the vector transduces retinal cells to produce functional retinoschisin protein.
Key features:
- AAV8 vector — selected for its high retinal transduction efficiency
- Subretinal delivery — targets the photoreceptor and retinal pigment epithelium layers
- One-time administration — designed for durable expression
Clinical Trial Design
| Parameter | Details |
|---|---|
| Lead Institution | West China Hospital, Sichuan University |
| Number of patients | 5 male patients with XLRS |
| Age range | 12–35 years |
| Dose | Single subretinal injection |
| Follow-up | 52 weeks |
Key Results
Efficacy
- Visual acuity — improvements in best-corrected visual acuity in 4 of 5 patients
- Optical coherence tomography (OCT) — reduction in schisis cavity size in treated eyes
- Visual field — stabilization or improvement in visual field parameters
- Retinoschisin expression — detectable retinoschisin protein levels in treated eyes
Safety
- No serious adverse events related to the vector
- No retinal detachment or other surgical complications
- No significant inflammation — manageable with standard immunosuppression
Significance for Inherited Retinal Diseases
This study represents a landmark achievement:
- First Chinese ophthalmic gene therapy published in NEJM — a testament to the quality of Chinese clinical research
- Proof of concept — demonstrates that AAV-mediated RS1 gene transfer is safe and can improve visual function in XLRS patients
- Platform validation — establishes a pathway for gene therapy in other inherited retinal diseases
- Global recognition — NEJM publication places Chinese ophthalmic gene therapy on the world stage