Safety and Efficacy Study of rAAV2-ND4 Treatment of Leber Hereditary Optic Neuropathy (LHON) (rAAV2-ND4)

• The Best Corrected Visual Acuity(BCVA) [ Time Frame: Up to 3 years ] [ Designated as safety issue: Yes ]
• Results of CD3/CD4/CD8 Test [ Time Frame: up to 6 months ] [ Designated as safety issue: Yes ]
  The mean percentage of CD3+/CD4+/CD8+ test before and after treatment

• Intraocular Pressure; [ Time Frame: Up to 3 years ] [ Designated as safety issue: Yes ]
• Neutralizing Antibody Assay [ Time Frame: up to 3 years ] [ Designated as safety issue: Yes ]
  The mean of Neutralizing antibody assay of 8 patients before and after treatment
• Average RNFL Thickness Througth Optical Coherence Tomography(OCT) Test [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
  Average RNFL thickness of 8 patients througth Optical coherence tomography(OCT) test before and after treatment
• Computerized Visual Field(MD: Mean Deviation, the Value Close to 0 Regarded Normal) [ Time Frame: up to 3 years ] [ Designated as safety issue: No ]
  MD: mean deviation, the value Close to 0 regarded normal.VFI/MD：The bigger one was more close to the normal value.
• Computerized Visual Field(VFI: Visual Field Index ,the Value Close to 100% Regarded Normal) [ Time Frame: up to 3 years ] [ Designated as safety issue: No ]
  VFI: visual field index ,the value Close to 100% regarded normal. VFI/MD：The bigger one was more close to the normal value.

• Intraocular pressure [ Time Frame: 6 month ] [ Designated as safety issue: Yes ]
  Intraocular pressure testing before and after treatment
• VEP [ Time Frame: 6 month ] [ Designated as safety issue: Yes ]
  VEP testing before and after treatment
• computerized visual field [ Time Frame: 6 month ] [ Designated as safety issue: No ]
  computerized visual field testing before and after treatment
• OCT [ Time Frame: 6 month ] [ Designated as safety issue: No ]
  OCT testing before and after treatment
• ERG [ Time Frame: 6 month ] [ Designated as safety issue: Yes ]
  ERG testing before and after treatment
• Liver and kidney function in plasma [ Time Frame: 6 month ] [ Designated as safety issue: Yes ]
  Liver and kidney function in plasma testing before and after treatment
• ELISA [ Time Frame: 6 month ] [ Designated as safety issue: Yes ]
  Antibodies against AAV2 capsid was analyzed by ELISA using serum samples collected before injection and different time points after the injection.

Leber's Hereditary Optic Neuropathy (LHON) is a maternally inherited ocular disorder associated with a mutation in mtDNA . The common manifestation is visual loss which caused by the respiratory chain enzymes complex dysfunction resulting in increased oxidative stress enzymes production.

Material and Method Seven patients with 11778 LHON mutation were randomly treated with a Single IVT Injection of recombinant Adeno-Associated Virus-NADH dehydrogenase, subunit 4 (complex I)（rAAV2-ND4)（0.05ml).The dose was 5 × 10^9 vg/0.05 mL for patients younger than 12 years old, and 1 × 10^10 vg/0.05 mL for patients older than 12 years old. The visual acuity, visual evoked potential （VEP）,optical coherence tomography（ OCT）, computerized visual field, electroretinograms(ERG), retinal nerve fiber layer(RNFL)and Liver and kidney function in plasma were compared before and after treatment at 1,3,and 6, months interval.

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Inclusion Criteria:

1. comply with Leber hereditary optic neuropathy diagnostic criteria.
2. in patients with informed consent, voluntary participation.
3. signed informed consent.
4. 8 ≤ Age ≤ 60 years old, good health, the patient can tolerate local anesthesia surgery.
5. to comply with doctor's instructions, can in the time of referral.

Exclusion Criteria:

1. Cardiopulmonary and renal function in severe weakness, cancer, a variety of bleeding disorders, acute sensing disease, high fever, high fever disease, women during pregnancy, heart disease, such as post-operative recovery period.
2. Are participating in other clinical studies of patients.
3. Patients with mental disorders.