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Efficacy and Safety of rAAV2-ND4 Treatment for Leber's Hereditary Optic Neuropathy.

Wan X, Pei H, Zhao MJ, Yang S, Hu WK, He H, Ma SQ, Zhang G, Dong XY, Chen C, Wang DW, Li B - Sci Rep (2016)

Bottom Line: The visual acuity of the injected eyes of six patients improved by at least 0.3 log MAR after 9 months of follow-up.No other outcome measure was significantly changed.None of the nine patients had local or systemic adverse events related to the vector during the 9-month follow-up period.

View Article: PubMed Central - PubMed

Affiliation: Department of Ophthalmology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

ABSTRACT
Leber's hereditary optic neuropathy (LHON) is a mitochondrially inherited disease leading to blindness. A mitochondrial DNA point mutation at the 11778 nucleotide site of the NADH dehydrogenase subunit 4 (ND4) gene is the most common cause. The aim of this study was to evaluate the efficacy and safety of a recombinant adeno-associated virus 2 (AAV2) carrying ND4 (rAAV2-ND4) in LHON patients carrying the G11778A mutation. Nine patients were administered rAAV2-ND4 by intravitreal injection to one eye and then followed for 9 months. Ophthalmologic examinations of visual acuity, visual field, and optical coherence tomography were performed. Physical examinations included routine blood and urine. The visual acuity of the injected eyes of six patients improved by at least 0.3 log MAR after 9 months of follow-up. In these six patients, the visual field was enlarged but the retinal nerve fibre layer remained relatively stable. No other outcome measure was significantly changed. None of the nine patients had local or systemic adverse events related to the vector during the 9-month follow-up period. These findings support the feasible use of gene therapy for LHON.

No MeSH data available.


Related in: MedlinePlus

Visual field of the injected eye of patient 4 at the 9-month follow-up.The visual field of the injected eye of patient 4 was gradually improved at 1, 3, 6, and 9 months after treatment, and the visual field at 6 months after treatment was the best.
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f3: Visual field of the injected eye of patient 4 at the 9-month follow-up.The visual field of the injected eye of patient 4 was gradually improved at 1, 3, 6, and 9 months after treatment, and the visual field at 6 months after treatment was the best.

Mentions: One month after intravitreal injection, patients 1, 4, and 6 reported an improvement in their visual field. Mean visual field index (VFI) of the injected eyes was 0.16 ± 0.18 before intravitreal injection, and 0.28 ± 0.23, 0.31 ± 0.23, 0.27 ± 0.22, and 0.27 ± 0.22 at months 1, 3, 6, and 9 after intravitreal injection, respectively (Figs 3 and 4). Mean defect (MD) of the injected eyes was improved at 6 and 9 months after intravitreal injection (Figs 3 and 5). Patient 2 refused the vision field test.


Efficacy and Safety of rAAV2-ND4 Treatment for Leber's Hereditary Optic Neuropathy.

Wan X, Pei H, Zhao MJ, Yang S, Hu WK, He H, Ma SQ, Zhang G, Dong XY, Chen C, Wang DW, Li B - Sci Rep (2016)

Visual field of the injected eye of patient 4 at the 9-month follow-up.The visual field of the injected eye of patient 4 was gradually improved at 1, 3, 6, and 9 months after treatment, and the visual field at 6 months after treatment was the best.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4759604&req=5

f3: Visual field of the injected eye of patient 4 at the 9-month follow-up.The visual field of the injected eye of patient 4 was gradually improved at 1, 3, 6, and 9 months after treatment, and the visual field at 6 months after treatment was the best.
Mentions: One month after intravitreal injection, patients 1, 4, and 6 reported an improvement in their visual field. Mean visual field index (VFI) of the injected eyes was 0.16 ± 0.18 before intravitreal injection, and 0.28 ± 0.23, 0.31 ± 0.23, 0.27 ± 0.22, and 0.27 ± 0.22 at months 1, 3, 6, and 9 after intravitreal injection, respectively (Figs 3 and 4). Mean defect (MD) of the injected eyes was improved at 6 and 9 months after intravitreal injection (Figs 3 and 5). Patient 2 refused the vision field test.

Bottom Line: The visual acuity of the injected eyes of six patients improved by at least 0.3 log MAR after 9 months of follow-up.No other outcome measure was significantly changed.None of the nine patients had local or systemic adverse events related to the vector during the 9-month follow-up period.

View Article: PubMed Central - PubMed

Affiliation: Department of Ophthalmology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

ABSTRACT
Leber's hereditary optic neuropathy (LHON) is a mitochondrially inherited disease leading to blindness. A mitochondrial DNA point mutation at the 11778 nucleotide site of the NADH dehydrogenase subunit 4 (ND4) gene is the most common cause. The aim of this study was to evaluate the efficacy and safety of a recombinant adeno-associated virus 2 (AAV2) carrying ND4 (rAAV2-ND4) in LHON patients carrying the G11778A mutation. Nine patients were administered rAAV2-ND4 by intravitreal injection to one eye and then followed for 9 months. Ophthalmologic examinations of visual acuity, visual field, and optical coherence tomography were performed. Physical examinations included routine blood and urine. The visual acuity of the injected eyes of six patients improved by at least 0.3 log MAR after 9 months of follow-up. In these six patients, the visual field was enlarged but the retinal nerve fibre layer remained relatively stable. No other outcome measure was significantly changed. None of the nine patients had local or systemic adverse events related to the vector during the 9-month follow-up period. These findings support the feasible use of gene therapy for LHON.

No MeSH data available.


Related in: MedlinePlus