Safety and Efficacy Study of Novel Gene Therapy ZM-01 for X-linked Retinoschisis Patients

X-linked retinoschisis (XLRS) is a rare, inherited retinal disease caused by mutations in the RS1 gene. Individuals affected by XLRS often experience progressive visual impairment from a young age, potentially leading to legal blindness. There is currently no established clinical treatment available. We developed an innovative adeno-associated virus (AAV)-based gene therapy for individuals with XLRS. Six to nine subjects with XLRS received a single unilateral intravitreal injection of ZM-01 at ascending doses.

Inclusion criteria

Subjects who meet all of the following criteria will be enrolled into the study

• Diagnosis of X-linked retinoschisis consistent with the presence of RS1 gene mutation
• Male, aged between 3 and 18 years old, in overall good health except for XLRS condition
• Capable of undergoing visual and retinal function assessment.
• The visual acuity of the study eye not better than: 0.4 (68 ETDRS letters equivalent)
• No carbonic anhydrase inhibitors have been used at present and for 3 months before treatment
• Laboratory tests meet the following criteria:

• Hemoglobin ≥ 11.0 g/dL
• White blood cell counts ranged from 3,300 to 12,000 cells /mm³;
• Platelet count 125,000-550,000 /mm³;
• Alanine aminotransferase (ALT) is not higher than 1.5 times the upper limit of the normal range of laboratory tests;
• Serum creatinine was no higher than 1.1 times the upper limit of the normal range for laboratory tests;
• Prothrombin time (PT) ≤14.5 seconds and partial thromboplastin time (PTT) ≤ 36.0 seconds.
• Willing to discontinue aspirin, aspirin-containing products, and any other medications that may alter clotting function at least 7 days before dosing.
• Be able to understand and sign informed consent.

Exclusion criteria

Subjects who meet any of the following exclusion criteria before enrollment were excluded from the study

• Previously received any AAV gene therapy
• The following mutations in RS1 gene: R141H, C59S or C223S
• Pre-existing eye conditions that cause severe vision loss or increase the risk of intravitreal injections (e.g., advanced glaucoma, uveitis, or severe retinal detachment)
• Ocular diseases in which there is opacity of the lens, cornea, or other media, hindering adequate observation and examination of the retina
• Use anticoagulant or antiplatelet drugs within 7 days before dosing
• Use any experimental drug within 3 months prior to registration
• Presented any situation that causes the investigator to believe the subject might not adhere to the study protocol or that participation might pose an unacceptable risk to the subject