Phase I trial of subretinal injection of a recombinant adeno-associated virus (rAAV2-VMD2-hMERTK) gene vector to patients with MERTK RP

Abstract

Purpose: To report short-term safety results of the phase I trial of subretinal injection of a rAAV2-VMD2-hMERTK gene vector for retinitis pigmentosa (RP) secondary to the MERTK Mutation

Methods: Except in one patient, the worst seeing eye of patients with MERTK mutation proven RP was injected with rAAV2-VMD2-hMERTK gene vector into the subretinal space. Patients underwent a full ophthalmic evaluation including early treatment diabetic retinopathy (ETDRS) visual acuity testing, slit-lamp and funduscopic evaluation, fundus photography, spectral-domain optical coherence tomography (SD-OCT), and full-field threshold stimulation test (FST). In addition, quality of life recordings, systemic evaluation and a battery of laboratory testing including AAV antibody and antigen specific reactivity as well as peripheral blood polymerase chain reaction (PCR) were performed at baseline and specific subsequent protocol visits. The vector injection was performed following a complete vitrectomy using a 39-gauge subretinal cannula.

Results: Six eyes of 6 enrolled patients have been injected so far. The age ranged from 15-50 years and the baseline visual acuity ranged from 20/40 Snellen equivalent to hand motion. The follow-up at the time of this writing ranged from 3-12 months. No intraoperative complications occurred. Postoperatively, one eye developed filamentary keratitis that resolved with lubrication, and another developed persistent submacular fluid that resolved spontaneously within 1 month with return of vision to baseline and subsequent improvement. Only one patient developed a rise in AAV antibodies but with a negative PCR. Three patients reported improved vision that was also documented on exam. In one of these, improvement in visual field was also reported and documented by field-testing compared to the fellow eye.

Conclusions: Subretinal injection of rAAV2-VMD2-hMERTK gene vector for patients with MERTK RP appears to be safe with no ocular or systemic side effects related to the vector itself. The treatment also appears to be beneficial in some cases.