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John Guy, William Feuer, Janet L Davis, Vittorio Porciatti, Philip Gonzalez, Rajeshwari D Koilkonda, Huijun Yuan, Byron L Lam; Gene Therapy for Leber Hereditary Optic NeuropathY An update of Where We Stand (Clinicaltrials.gov number: NCT02161380). Invest. Ophthalmol. Vis. Sci. 2019;60(9):3602.
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© ARVO (1962-2015); The Authors (2016-present)
To update our safety and visual results after a single unilateral, intravitreal injection of low, medium and high dose self-complementary adeno-associated virus serotype 2(scAAV2) containing a wild-type synthetic nuclear encoded ND4 subunit to G11778A Leber hereditary optic neuropathy (LHON) subjects.
Design/Methods: Dose-escalation study investigating three groups reflecting their stage of LHON: Group I (chronic). Bilateral acuity loss to ≤ 30 ETDRS letters (Snellen = 20/252) in both eyes for more than 12 months. Group II (acute). Bilateral loss to ≤ 30 ETDRS letters in both eyes for less than 12 months. Three patients in each group received a low dose and 3 received a medium dose. Three patients in group I received a high dose. Group III (unilateral). Acute unilateral loss of acuity to <30 ETDRS letters in one eye, but with good acuity ≥ 70 letters in the contralateral eye. Groups I and II, the eye with worse acuity is injected, for group III the eye with better acuity is injected. Titers of vector are as follows:Low dose =1.18 x 109 vg,Medium dose =5.81 x 109 vgHigh dose =2.4 x 1010 vgHigher dose= 1.0 x 1011 vgParticipants are monitored through out a three year evaluation period for occurrence of AEs (acute, delayed, and/or cumulative),as well as for changes in clinical status, and visual acuity status. Safety and efficacy assessments are performed on days 1, and 7 post-injection and 1, 2, 3, 6,12,18, 24 and 36 months post-injection.
The visual results (logMAR) of Group I are shown in Table I. Low and medium dose injection patients have been followed for 3 years. High dose patients were recently injected and had much shorter follow-up.Visual results of group II are shown in Table II. Most completed 2 years of follow-up.Visual results of group III are shown in Table III. Most completed at least one year of follow-up.No concerning systemic adverse events were observed. Three eyes developed mild and asymptomatic uveitis that resolved spontaneously without treatment.
Having completed low, medium and high dose escalation injections with 1-3 years of follow-up, we are now ready to recruit patients for injection of the highest dose (1×1011 vg).
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
LogMar Acuities of Injected and Fellow eyes- BL= baseline examinations prior to injections
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