Abstract
Objective: To report the effects of gene therapy for G11778A LHON.
Background: We are conducting an open-label, unilateral single-dose, ocular injection of scAAV2 containing a nuclear-encoded ND4 gene.
Design/Methods: Six patients with bilateral acuity loss for more than a year received a low (5 x e9 vg) (n=3) or medium dose (2.46× e10 vg) (n=3) into the eye with worse acuity. An additional six patients with bilateral vision loss for less than a year received the low (n=3) or medium dose (n=3). Clinical testing included ETDRS visual acuity, visual fields, OCT, pattern ERG and neuro-ophthalmic examinations. GEE methods were used for longitudinal analyses.
Results: When improvement of visual acuity in injected eyes was compared to fellow eyes using all measurements from day 1 through month 18, injected eye improvement was significantly greater than fellow eye improvement (p=0.039). A post-hoc comparison found the differences between study eye minus fellow eye improvement in gene therapy patients (0.69 logMAR units) was greater than that of the natural history (0.21 logMAR units) (p=0.012) (JAMA Ophthalmol 132:428–436). 0.1LogMAR=5 EDTRS letters. Two patients developed asymptomatic uveitis that resolved without treatment. One was treated with low dose, the other with medium dose. Two additional patients with ≤20/200 vision loss in one eye were treated before loss of vision in the fellow eye. For one with 5 letters in the bad eye, low-dose did not prevent a drop from 80 to 60 letters at month 3 and to 5 letters at month6. In another unilateral case the fellow eye increased to 84 letters at month 3 relative to 77 letters at entry. No difference between eyes in outcomes of other visual function measures was detected. Virus was not detected in blood. Nabs to AAV were detected in all patients before and after treatment.
Conclusions: These results support testing of the high dose next.
Study Supported by:
1U10EY023558
1U10EY024247
Disclosure: Dr. Guy has nothing to disclose. Dr. Feuer has nothing to disclose. Dr. Davis has nothing to disclose. Dr. Porciatti has nothing to disclose. Dr. Gonzalez has nothing to disclose. Dr. Koilkonda has nothing to disclose. Dr. Yuan has nothing to disclose. Dr. Lam has nothing to disclose.
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