June 2015
Volume 56, Issue 7
ARVO Annual Meeting Abstract  |   June 2015
Leber Hereditary Optic Neuropathy Gene Therapy (LHON) Clinical Trial: Initial Results
Author Affiliations & Notes
  • John Guy
    Bascom Palmer Eye Institute, Miami, FL
  • William J Feuer
    Bascom Palmer Eye Institute, Miami, FL
  • Vittorio Porciatti
    Bascom Palmer Eye Institute, Miami, FL
  • William W Hauswirth
    Ophthalmology, University of Florida, Gainesville, FL
  • Janet L Davis
    Bascom Palmer Eye Institute, Miami, FL
  • Byron L Lam
    Bascom Palmer Eye Institute, Miami, FL
  • Rajeshwari D Koilkonda
    Bascom Palmer Eye Institute, Miami, FL
  • Huijun Yuan
    Bascom Palmer Eye Institute, Miami, FL
  • Phillip Gonzalez
    Bascom Palmer Eye Institute, Miami, FL
  • Anil Lalwani
    Bascom Palmer Eye Institute, Miami, FL
  • Footnotes
    Commercial Relationships John Guy, None; William Feuer, None; Vittorio Porciatti, None; William Hauswirth, AGTC (F); Janet Davis, None; Byron Lam, None; Rajeshwari Koilkonda, None; Huijun Yuan, None; Phillip Gonzalez, None; Anil Lalwani, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2015, Vol.56, 2608. doi:
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      John Guy, William J Feuer, Vittorio Porciatti, William W Hauswirth, Janet L Davis, Byron L Lam, Rajeshwari D Koilkonda, Huijun Yuan, Phillip Gonzalez, Anil Lalwani; Leber Hereditary Optic Neuropathy Gene Therapy (LHON) Clinical Trial: Initial Results. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):2608.

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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose: To determine the safety and tolerability of AAV2(Y444,500,703F)-P1ND4v2 (a nuclear encoded version wild-type ND4 imported into the mitochondria with the addition of a targeting sequence) in patients with LHON.

Methods: After obtaining informed consent for participation in this open-label, unilateral single-dose, intravitreal injection of AAV2(Y444,500,703F)-P1ND4v2 per subject in a dose-escalation study designed to investigate the safety of three vector doses (5x109 vg, 2.46x1010 vg and 1x1011 vg) in subjects with molecularly confirmed G11778A-mutated mitochondrial DNA; two patients with long-standing (>12 months) and bilateral acuity loss down to ≤ 35 ETDRS letters (20/200) received intravitreal injections of low dose study drug (5x109 vg) into the eye with worse acuity. Clinical testing included ETDRS visual acuity, Humphrey visual fields (30-2), OCT, pattern ERG (PERG) and neuro-ophthalmic examinations. Blood samples were screened for neutralizing antibodies (Nabs) to AAV2 prior and after intravitreal injection. Postinjection evaluations thus far are 1 month in the first patient and one week in the second patient.

Results: Visual acuity of patient 1 was hand movements prior to injection and remained at that level one day, one week and 1-2 months after injection. No haze, cells or inflammation was detected in the vitreous or anterior chamber and retinal examination remained normal showing only optic atrophy . RNFL was 54 µm prior to injection and 56 µm after injection. HVF MD remained -32.8. PERG amplitudes were 0.17 µV, within noise levels, prior to injection and 0.27 µV after injection . Visual acuity of patient 2 was counting fingers prior to and one week after injection. PERG amplitudes were 0.45 -0.48 µV prior to injection and 0.57 µV 1 week postinjection. Both patients had NAb titers of 1:20,480 prior to injection that did not change after injection. Vector genomes were not detected in the blood.

Conclusions: Thus far study drug appears to be safe and well-tolerated. After the 3rd patient is injected we will evaluate the higher doses in this chronic cohort then evaluate safety in subjects with a) acute (<12 months) bilateral loss of visual acuity to < 35 ETDRS letters and b) with acute (<12 months) unilateral loss of acuity to <35 ETDRS letters, but who have “good acuity” ≥ 70 letters (20/40) in the contralateral eye with better acuity selected for injection.


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